Bioactive Proteins and Peptides as Functional Foods and Nutraceuticals (Institute of Food Technologists Series)

Bioactive Proteins and Peptides as Functional Foods and Nutraceuticals Yoshinori Mine, Eunice Li-Chan, and Bo Jiang EDITORS

A John Wiley & Sons, Inc., Publication

Bioactive Proteins and Peptides as Functional Foods and Nutraceuticals

The IFT Press series reflects the mission of the Institute of Food Technologists—to advance the science of food contributing to healthier people everywhere. Developed in partnership with Wiley-Blackwell, IFT Press books serve as leading-edge handbooks for industrial application and reference and as essential texts for academic programs. Crafted through rigorous peer review and meticulous research, IFT Press publications represent the latest, most significant resources available to food scientists and related agriculture professionals worldwide. Founded in 1939, the Institute of Food Technologists is a nonprofit scientific society with 22,000 individual members working in food science, food technology, and related professions in industry, academia, and government. IFT serves as a conduit for multidisciplinary science through leadership, championing the use of sound science across the food value chain through knowledge sharing, education, and advocacy. IFT Book Communications Committee Syed S. H. Rizvi Casimir C. Akoh Barry G. Swanson Christopher J. Doona Ruth M. Patrick Mark Barrett Heather Troxell Karen Nachay IFT Press Editorial Advisory Board Malcolm C. Bourne Dietrich Knorr Theodore P. Labuza Thomas J. Montville S. Suzanne Nielsen Martin R. Okos Michael W. Pariza Barbara J. Petersen David S. Reid Sam Saguy Herbert Stone Kenneth R. Swartzel

A John Wiley & Sons, Inc., Publication

Bioactive Proteins and Peptides as Functional Foods and Nutraceuticals Yoshinori Mine, Eunice Li-Chan, and Bo Jiang EDITORS

A John Wiley & Sons, Inc., Publication

Edition first published 2010 © 2010 Blackwell Publishing Ltd. and Institute of Food Technologists Blackwell Publishing was acquired by John Wiley & Sons in February 2007. Blackwell’s publishing program has been merged with Wiley’s global Scientific, Technical, and Medical business to form Wiley-Blackwell. Editorial Office 2121 State Avenue, Ames, Iowa 50014-8300, USA For details of our global editorial offices, for customer services, and for information about how to apply for permission to reuse the copyright material in this book, please see our Website at www.wiley.com/wiley-blackwell. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by Blackwell Publishing, provided that the base fee is paid directly to the Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923. For those organizations that have been granted a photocopy license by CCC, a separate system of payments has been arranged. The fee code for users of the Transactional Reporting Service is ISBN-13: 978-0-8138-1311-0/2010. Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks, or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought. Library of Congress Cataloging-in-Publication Data Bioactive proteins and peptides as functional foods and nutraceuticals / edited by Yoshinori Mine, Eunice Li-Chan, and Bo Jiang. – 1st ed. p. ; cm. Includes bibliographical references and index. ISBN 978-0-8138-1311-0 (alk. paper) 1. Proteins in human nutrition. 2. Functional foods. I. Mine, Yoshinori. II. Li-Chan, Eunice. III. Jiang, Bo, 1962– [DNLM: 1. Dietary Proteins–metabolism. 2. Peptides–metabolism. 3. Dietary Proteins–analysis. 4. Nutritional Physiological Phenomena. 5. Peptides–analysis. QU 55.4 B615 2010] TX553.P7B65 2010 612.3′98–dc22 2009054220 A catalog record for this book is available from the U.S. Library of Congress. Set in 10 on 12 pt Times by Toppan Best-set Premedia Limited Printed in Singapore Disclaimer The publisher and the author make no representations or warranties with respect to the accuracy or completeness of the contents of this work and specifically disclaim all warranties, including without limitation warranties of fitness for a particular purpose. No warranty may be created or extended by sales or promotional materials. The advice and strategies contained herein may not be suitable for every situation. This work is sold with the understanding that the publisher is not engaged in rendering legal, accounting, or other professional services. If professional assistance is required, the services of a competent professional person should be sought. Neither the publisher nor the author shall be liable for damages arising herefrom. The fact that an organization or Website is referred to in this work as a citation and/or a potential source of further information does not mean that the author or the publisher endorses the information the organization or Website may provide or recommendations it may make. Further, readers should be aware that Internet Websites listed in this work may have changed or disappeared between when this work was written and when it is read. 1

2010

Titles in the IFT Press series • Accelerating New Food Product Design and Development (Jacqueline H. Beckley, Elizabeth J. Topp, M. Michele Foley, J.C. Huang, and Witoon Prinyawiwatkul) • Advances in Dairy Ingredients (Geoffrey W. Smithers and Mary Ann Augustin) • Biofilms in the Food Environment (Hans P. Blaschek, Hua H. Wang, and Meredith E. Agle) • Calorimetry and Food Process Design (Gönül Kaletunç) • Food Ingredients for the Global Market (Yao-Wen Huang and Claire L. Kruger) • Food Irradiation Research and Technology (Christopher H. Sommers and Xuetong Fan) • Foodborne Pathogens in the Food Processing Environment: Sources, Detection and Control (Sadhana Ravishankar, Vijay K. Juneja, and Divya Jaroni) • High Pressure Processing of Foods (Christopher J. Doona and Florence E. Feeherry) • Hydrocolloids in Food Processing (Thomas R. Laaman) • Improving Import Food Safety (Wayne C. Ellefson, Lorna Zach, and Darryl Sullivan) • Microbial Safety of Fresh Produce: Challenges, Perspectives and Strategies (Xuetong Fan, Brendan A. Niemira, Christopher J. Doona, Florence E. Feeherry, and Robert B. Gravani) • Microbiology and Technology of Fermented Foods (Robert W. Hutkins) • Multiphysics Simulation of Emerging Food Processing Technologies (Kai Knoerzer, Pablo Juliano, Peter Roupas, and Cornelis Versteeg) • Multivariate and Probabilistic Analyses of Sensory Science Problems (Jean-François Meullenet, Rui Xiong, and Christopher J. Findlay • Nanoscience and Nanotechnology in Food Systems (Hongda Chen) • Natural Food Flavors and Colorants (Mathew Attokaran) • Nondestructive Testing of Food Quality (Joseph Irudayaraj and Christoph Reh) • Nondigestible Carbohydrates and Digestive Health (Teresa M. Paeschke and William R. Aimutis) • Nonthermal Processing Technologies for Food (Howard Q. Zhang, Gustavo V. Barbosa-Cànovas, V.M. Balasubramaniam, Editors; C. Patrick Dunne, Daniel F. Farkas, James T.C. Yuan, Associate Editors) • Nutraceuticals, Glycemic Health and Type 2 Diabetes (Vijai K. Pasupuleti and James W. Anderson) • Organic Meat Production and Processing (Steven C. Ricke, Michael G. Johnson, and Corliss A. O’Bryan) • Packaging for Nonthermal Processing of Food (J. H. Han) • Preharvest and Postharvest Food Safety: Contemporary Issues and Future Directions (Ross C. Beier, Suresh D. Pillai, and Timothy D. Phillips, Editors; Richard L. Ziprin, Associate Editor) • Processing and Nutrition of Fats and Oils (Ernesto M. Hernandez, and Afaf Kamal-Eldin) • Processing Organic Foods for the Global Market (Gwendolyn V. Wyard, Anne Plotto, Jessica Walden, and Kathryn Schuett) • Regulation of Functional Foods and Nutraceuticals: A Global Perspective (Clare M. Hasler) • Resistant Starch: Sources, Applications and Health Benefits (Yong-Cheng Shi and Clodualdo Maningat) • Sensory and Consumer Research in Food Product Design and Development (Howard R. Moskowitz, Jacqueline H. Beckley, and Anna V.A. Resurreccion) • Sustainability in the Food Industry (Cheryl J. Baldwin) • Thermal Processing of Foods: Control and Automation (K. P. Sandeep) • Trait-Modified Oils in Foods (Frank T. Orthoefer and Gary R. List) • Water Activity in Foods: Fundamentals and Applications (Gustavo V. Barbosa-Cànovas, Anthony J. Fontana Jr., Shelly J. Schmidt, and Theodore P. Labuza) • Whey Processing, Functionality and Health Benefits (Charles I. Onwulata and Peter J. Huth)

Contents

Preface, ix Contributors, xi Part 1. Introduction, 3 1.

Biologically Active Food Proteins and Peptides in Health: An Overview, 5 Yoshinori Mine, Eunice C.Y. Li-Chan, and Bo Jiang

Part 2. Functions of Biologically Active Proteins and Peptides, 13 2.

Anti-inflammatory/Oxidative Stress Proteins and Peptides, 15 Denise Young and Yoshinori Mine

3.

Antioxidant Peptides, 29 Youling L. Xiong

4.

Antihypertensive Peptides and Their Underlying Mechanisms, 43 Toshiro Matsui and Mitsuru Tanaka

5.

Food Protein–Derived Peptides as Calmodulin Inhibitors, 55 Rotimi E. Aluko

6.

Soy Protein for the Metabolic Syndrome, 67 Cristina Martínez-Villaluenga and Elvira González de Mejía

7.

Amyloidogenic Proteins and Peptides, 87 Soichiro Nakamura, Takanobu Owaki, Yuki Maeda, Shigeru Katayama, and Kosuke Nakamura

8.

Peptide-Based Immunotherapy for Food Allergy, 101 Marie Yang and Yoshinori Mine

9.

Gamma-Aminobutyric Acid, 121 Bo Jiang, Yuanxin Fu, and Tao Zhang

10.

Food Proteins or Their Hydrolysates as Regulators of Satiety, 135 Martin Foltz, Mylene Portier, and Daniel Tomé

Part 3. Examples of Food Proteins and Peptides with Biological Activity, 149 11.

Health-Promoting Proteins and Peptides in Colostrum and Whey, 151 Hannu J. Korhonen vii

viii

Contents

12.

Functional Food Products with Antihypertensive Effects, 169 Naoyuki Yamamoto

13.

Secreted Lactoferrin and Lactoferrin-Related Peptides: Insight into Structure and Biological Functions, 179 Dominique Legrand, Annick Pierce, and Joël Mazurier

14.

Bioactive Peptides and Proteins from Fish Muscle and Collagen, 203 Nazlin K. Howell and Chitundu Kasase

15.

Animal Muscle-Based Bioactive Peptides, 225 Jennifer Kovacs-Nolan and Yoshinori Mine

16.

Processing and Functionality of Rice Bran Proteins and Peptides, 233 Rashida Ali, Frederick F. Shih, and Mian Nadeem Riaz

17.

Bioactive Proteins and Peptides from Egg Proteins, 247 Jianping Wu, Kaustav Majumder, and Kristen Gibbons

18.

Soy Peptides as Functional Food Materials, 265 Toshihiro Nakamori

19.

Bioactivity of Proteins and Peptides from Peas (Pisum sativum, Vigna unguiculata, and Cicer arietinum L), 273 Bo Jiang, Wokadala C. Obiro, Yanhong Li, Tao Zhang, and Wanmeng Mu

20.

Wheat Proteins and Peptides, 289 Hitomi Kumagai

Part 4. Recent Advances in Bioactive Peptide Analysis for Food Application, 305 21.

Peptidomics for Bioactive Peptide Analysis, 307 Icy D’Siva and Yoshinori Mine

22.

In silico Analysis of Bioactive Peptides, 325 Marta Dziuba and Bartłomiej Dziuba

23. Flavor-Active Properties of Amino Acids, Peptides, and Proteins, 341 Eunice C.Y. Li-Chan and Imelda W.Y. Cheung 24. Controlled Release and Delivery Technology of Biologically Active Proteins and Peptides, 359 Idit Amar-Yuli, Abraham Aserin, and Nissim Garti Index, 383

Preface

Functional proteins and peptides are now an important category within the nutraceuticals food sector. A growing body of scientific evidence in the past decade has revealed that many food proteins and peptides exhibit specific biological activities in addition to their established nutritional value. Bioactive peptides present in foods may help reduce the worldwide epidemic of chronic diseases that account for 58 million premature deaths annually. This book aims to compile current science-based advances on biologically active food proteins and peptides for health promotion and reduction of risk of chronic diseases. The book is comprised of four parts: (1) “Introduction,” (2) “Functions of Biologically Active Proteins and Peptides,” (3) “Examples of Food Proteins and Peptides with Biological Activity,” and (4) “Recent Advances in Bioactive Peptide Analysis for Food Application.” The book considers fundamental concepts and structure-activity relations for the major classes of nutraceutical proteins and peptides. The international team from industry and academia also contributed current applications and future opportunities within the nutraceutical proteins and peptides of rapidly growing fields in food and nutrition research

and conveys the state of the science to date. We are grateful to all the stellar internationally renowned authors for their state-of-the-art compilation of recent rapid developments in this field, which made the publication of this book possible. We believe that this book deserves a broad readership in the disciplines of food science, nutrition, pharmaceuticals, cosmetics, nutraceutical/functional foods, biochemistry, and biotechnology. This book could also be useful as a comprehensive reference book by senior undergraduate and graduate students, as well as by the nutraceutical and pharmaceutical industries. We wish to thank all the contributors for sharing their expertise throughout our journey. We also thank the reviewers for giving their valuable comments on improving the contents of each chapter. All these professionals are the ones who made this book possible. We thank members of the production team at Wiley-Blackwell for their time, effort, advice, and expertise. Yoshinori Mine Eunice C.Y. Li-Chan Bo Jiang

ix

Contributors

Rashida Ali Division of Food Research H.E.J. Research Institute of Chemistry International Centre for Chemical and Biological Sciences University of Karachi Karachi-75270, Pakistan Rotimi E. Aluko University of Manitoba Department of Human Nutritional Sciences Winnipeg, Canada R3T 2N2 [email protected] Phone: 204-474-9555; Fax: 204-474-7593 Idit Amar-Yuli Casali Institute of Applied Chemistry Givat Ram Campus The Hebrew University of Jerusalem Jerusalem 91904, Israel Abraham Aserin Casali Institute of Applied Chemistry Givat Ram Campus The Hebrew University of Jerusalem Jerusalem 91904, Israel Imelda W.Y. Cheung The University of British Columbia Food Nutrition & Health Program 2205 East Mall Vancouver, BC, Canada V6T 1Z4

Icy D’Siva Department of Food Science University of Guelph Guelph, ON, Canada N1G 2W1 Bartłomiej Dziuba University of Warmia and Mazury Faculty of Food Science Chair of Industrial and Food Microbiology Pl. Cieszynski 1 10-712 Olsztyn-Kortowo, Poland Marta Dziuba University of Warmia and Mazury Faculty of Food Science Chair of Food Biochemistry Pl. Cieszynski 1 10-712 Olsztyn-Kortowo, Poland Martin Foltz Unilever R&D Vlaardingen Olivier van Noortlaan 120 3133 AT Vlaardingen The Netherlands Yuanxin Fu State Key Laboratory of Food Science and Technology Jiangnan University 1800 Lihu Avenue Wuxi, Jiangsu 214122, China

xi

xii

Contributors

Nissim Garti Casali Institute of Applied Chemistry Givat Ram Campus The Hebrew University of Jerusalem Jerusalem 91904, Israel [email protected] Phone: 972-2-658-6574/5; Fax: 972-2-652-0262 Kristen Gibbons Department of Agricultural, Food and Nutritional Science University of Alberta Edmonton, AB, Canada T6G 2P5 Elvira González de Mejía Department of Food Science & Human Nutrition Division of Nutritional Sciences University of Illinois at Urbana-Champaign 228 Edward R Madigan Laboratory, 1201 W. Gregory Drive Urbana, IL 61801 [email protected] Phone: 217-244-3196; 217-244-3198 Nazlin K. Howell Professor of Food Biochemistry University of Surrey Faculty of Health and Medical Sciences Guildford, Surrey GU2 7XH [email protected] Phone: +44 1483 686448 Bo Jiang State Key Laboratory of Food Science and Technology Jiangnan University Jiangsu, 214122, China [email protected] Phone: +86-510-85329055; Fax: +86-510-85919625 Chitundu Kasase University of Surrey Faculty of Health and Medical Sciences Guildford, Surrey GU2 7XH, UK

Shigeru Katayama Department of Bioscience and Biotechnology Shinshu University 8304 Minamiminowamura Ina, Nagano 399-4598, Japan Hannu J. Korhonen MTT Agrifood Research Finland Biotechnology and Food Research FIN-31600 Jokioinen, Finland [email protected] Phone: +358-3-41883271; Fax: +358-3-41883244 Jennifer Kovacs-Nolan Department of Food Science University of Guelph Guelph, ON, Canada N1G 2W1 Hitomi Kumagai College of Bioresource Sciences Nihon University [email protected] Phone/Fax: +81-466-84-3946 Dominique Legrand Unité de Glycobiologie Structurale et Fonctionnelle Université des Sciences et Technologies de Lille UMR No. 8576 du CNRS / IFR 147 F-59655 Villeneuve d’Ascq Cedex, France [email protected] Phone: 33-3-20-43-44-30; Fax: 33-3-20-43-65-55 Yanhong Li State Key Laboratory of Food Science and Technology Jiangnan University 1800 Lihu Avenue Wuxi, Jiangsu 214122, China Eunice C.Y. Li-Chan The University of British Columbia Food Nutrition & Health Program 2205 East Mall Vancouver, BC, Canada V6T 1Z4 [email protected] Phone: 1-604-822-6182; Fax: 1-604-822-5143

Contributors

Yuki Maeda Department of Bioscience and Biotechnology Shinshu University 8304 Minamiminowamura Ina, Nagano 399-4598, Japan Kaustav Majumder Department of Agricultural, Food and Nutritional Science University of Alberta Edmonton, AB, Canada T6G 2P5 Cristina Martínez-Villaluenga Department of Food Science & Human Nutrition Division of Nutritional Sciences University of Illinois at Urbana-Champaign 228 Edward R Madigan Laboratory, 1201 W. Gregory Drive Urbana, IL 61801 Toshiro Matsui Faculty of Agriculture Graduate School of Kyushu University Fukuoka, 812-8581, Japan [email protected] Phone: +81-92-642-3012 Joël Mazurier Unité de Glycobiologie Structurale et Fonctionnelle Université des Sciences et Technologies de Lille UMR No. 8576 du CNRS / IFR 147 F-59655 Villeneuve d’Ascq Cedex, France Yoshinori Mine Department of Food Science University of Guelph Guelph, ON, Canada N1G 2W1 [email protected] Phone: 519-824-4120 x52901; Fax: 519-824-6631 Wanmeng Mu State Key Laboratory of Food Science and Technology Jiangnan University 1800 Lihu Avenue Wuxi, Jiangsu 214122, China

xiii

Toshihiro Nakamori Fuji Oil Co., Ltd, 1 Sumiyoshi-Cho Izumisano-Shi, Osaka 598-8540, Japan [email protected] Phone: +81-297-52-6322; Fax: +81-297-52-6320 Kosuke Nakamura The Japan Health Sciences Foundation 13-4 Nihonbashi Kodenma-cho Chuo-ku, Tokyo 103-0001, Japan Soichiro Nakamura Department of Bioscience and Biotechnology Shinshu University 8304 Minamiminowamura Ina, Nagano 399-4598, Japan Wokadala C. Obiro State Key Laboratory of Food Science and Technology Jiangnan University 1800 Lihu Avenue Wuxi, Jiangsu 214122, China Takanobu Owaki Department of Bioscience and Biotechnology Shinshu University 8304 Minamiminowamura Ina, Nagano 399-4598, Japan Annick Pierce Unité de Glycobiologie Structurale et Fonctionnelle Université des Sciences et Technologies de Lille UMR No. 8576 du CNRS / IFR 147 F-59655 Villeneuve d’Ascq Cedex, France Myléne Potier AgroParisTech Life Sciences and Health 16 rue Claude Bernard 75005 Paris, France

xiv

Contributors

Mian Nadeem Riaz United States Department of Agriculture (USDA)-ARS-SRRC New Orleans, LA 70124 Frederick F. Shih English Biscuit Manufacturers (Private) Limited Korangi Industrial Area Karachi, Pakistan Mitsuru Tanaka Faculty of Agriculture Graduate School of Kyushu University Fukuoka, 812-8581, Japan Daniel Tomé AgroParisTech Life Sciences and Health 16 rue Claude Bernard 75005 Paris, France Jianping Wu Department of Agricultural, Food and Nutritional Science University of Alberta Edmonton, AB, Canada T6G 2P5 [email protected] Phone: 780-492-6885; Fax: 780-492-4346

Youling L. Xiong University of Kentucky Department of Animal and Food Sciences Room 206 W.P. Garrigus Bldg. Lexington, KY 40546-0215 [email protected] Phone: 859-257-3822 Naoyuki Yamamoto R&D Center Calpis Co., Ltd. 11-10, 5-Chome, Fuchinobe, Sagamihara, Kanagawa 229 Japan [email protected] Marie Yang Department of Food Science University of Guelph Guelph, ON, Canada N1G 2W1 Denise Young Department of Food Science University of Guelph Guelph, ON, Canada N1G 2W1 Tao Zhang State Key Laboratory of Food Science and Technology Jiangnan University Wuxi, Jiangsu 214122, China

Bioactive Proteins and Peptides as Functional Foods and Nutraceuticals

Part 1 Introduction

Chapter 1 Biologically Active Food Proteins and Peptides in Health: An Overview Yoshinori Mine, Eunice C.Y. Li-Chan, and Bo Jiang

A growing body of scientific evidence in the past decade has revealed that many food proteins and peptides exhibit specific biological activities in addition to their established nutritional value (Mine and Shahidi 2006; Hartmann and Meisel 2007; Tripathi and Vashishtha 2006; Yalcin 2006; Möller et al. 2008). Bioactive peptides have been found in enzymatic protein hydrolysates and fermented dairy products, but they can also be released during gastrointestinal digestion of proteins (Meisel 2005; Korhonen and Pihlanto 2007a, 2007b; Gobbetti et al. 2007; Hartmann and Meisel 2007). Bioactive peptides may help reduce the worldwide epidemic of chronic diseases that account for 58 million premature deaths annually. Functional proteins and peptides are an important category within the nutraceuticals food sector currently valued at $75 billion/ year. Nevertheless, several challenges should be addressed to allow sustained growth within this sector. Some earlier health benefits claimed for protein nutraceuticals were based on in vitro models or limited clinical trials leading to equivocal findings (Möller et al. 2008). Technological and fundamental problems remain in relation to large-scale production, compatibility with different food matrices, gastrointestinal stability, bioavailability, and long-term safety (Murray and FitzGerald 2007; Mine 2007). Research into consumer perception and Bioactive Proteins and Peptides as Functional Foods and Nutraceuticals, Edited by Yoshinori Mine, Eunice Li-Chan, and Bo Jiang. © 2010 Blackwell Publishing Ltd. and Institute of Food Technologists

legislation is also necessary. Nutritionists, biomedical scientists, food scientists, and technologists are working together to develop improved systems for discovery, testing, and validation of nutraceutical proteins and peptides with increased potency and therapeutic benefits. Bioactive peptides and proteins are being developed that positively impact on body function and human health by alleviating conditions such as coronary (ischemic) heart disease, stroke, hypertension, cancer, obesity, diabetes, and osteoporosis. Screening novel bioactive sources using high-throughput ohmics technologies, specific disease biomarkers, and comprehensive clinical trials will facilitate the development of nutraceutical proteins and peptides for a further range of health conditions (Gilani et al. 2008; Mine et al. 2009; Boelsma and Kloek 2009). This book aims to compile current science-based advances on biologically active food proteins and peptides for health promotion and reduction of the risk of chronic diseases. The book is comprised of four parts: (1) Introduction, (2) Functions of Biologically Active Proteins and Peptides, (3) Examples of Food Proteins and Peptides with Biological Activity, and (4) Recent Advances in Bioactive Peptide Analysis for Food Application. Chapter 1 summarizes aims and scope as well as overall highlights of this book. Chapters 2 and 3 highlight antioxidative and anti-inflammatory proteins and peptides. Oxidative stress is a biological state that occurs when a cell’s antioxidant capacity is overwhelmed by reactive oxygen species (ROS), causing a redox imbalance. Oxidative stress and 5

6

Part 1 Introduction

inflammation are often related to chronic diseases involving the cardiovascular, neurological, and gastrointestinal systems. Proteins and peptides have been found not only to contribute to the body’s energy supply and growth but also to influence specific biological activities such as oxidative stress and inflammation. As our understanding of the efficacy and mechanism of action of antioxidative stress and anti-inflammatory proteins and peptides increases, so will the growing interest in their prophylactic, preventive, and therapeutic uses. Recent advances in peptide research have led to the accumulation of mounting evidence that many endogenous peptides have the biological function to stabilize radicals and neutralize other nonradical oxidizing species. Furthermore, this biological function has been demonstrated by in vitro digests of proteins. With an improved understanding of the structure-function relationship, it is now possible to develop antioxidant peptides and peptide mixtures through enzymatic or microbial hydrolysis of common food proteins or by means of chemical synthesis. While the question of whether peptides can act as antioxidants no longer remains, it is still a big challenge to identify the fate of dietary antioxidant peptides and their exact biological activity once entering the circulation system and crossing the cell membrane. The production cost as well as the potential allergenicity of antioxidant peptides must also be assessed in the continuing effort to develop such novel antioxidants to complement the human body’s natural defense system, including antioxidant enzymes, vitamins, and nonprotein compounds. Chapter 4 reviews the updated antihypertensive mechanism as well as the development of antihypertensive food products. The efficacy of peptide intake for borderline hypertensives is evidentially developed on the basis of extensive intervention trials, but such an effective foods for specified health use (FOSHU) produce has led to the question of whether the antihypertensive effect of peptides is achieved only by angiotensin-converting enzyme (ACE) inhibition or suppression of the renin-angiotensin system, like therapeutic ACE inhibitory drugs. Peptide research on this topic has become one of the growing fields in preventative medicinal chemistry,

since clinical evidence demonstrated the efficacy of peptide intake for improving the treatment of hypertension. Chapter 5 presents food protein–derived bioactive peptides as inhibitors for calmodulin (CaM), a protein that plays important roles in maintaining physiological functions of cells and body organs. Current knowledge indicates that CaM-binding peptides can be produced through the enzymatic hydrolysis of food proteins followed by separation and purification of cationic peptides. Inhibition of CaMdependent enzymes seems to be dependent mostly on the level of basic (positively charged) amino acid residues for short-chain ( 135 mmHg and/or diastolic blood pressure [DBP] > 85 mmHg) was ca. 55 million in 2006 (Japanese Ministry of Health, Labour and Welfare). In the case of essential hypertension, which afflicts >90% of all hypertensions, the onset followed by

Bioactive Proteins and Peptides as Functional Foods and Nutraceuticals, Edited by Yoshinori Mine, Eunice Li-Chan, and Bo Jiang. © 2010 Blackwell Publishing Ltd. and Institute of Food Technologists

4.2. Regulation of Vascular Events by Dipeptides, 47 4.3. Relaxation of Vascular Constrictive Events by Dipeptides, 48 5. Future Prospects, 51 6. References, 53

cardiovascular disease, renal dysfunction, or peripheral vascular disease is closely associated with lifeand/or food-style, including excess high-salt intake (Kawano et al. 2007). Namely, disruption of Na+-K+ balance or increase in fluid volume as well as increasing vascular resistance will lead to promotion of blood pressure (BP). The most beneficial improvement for essential/borderline hypertension is, therefore, said to be one that achieves modification of food-style and/or moderate exercise. In addition to such lifestyle modification treatments, peptide research has become one of the growing fields for preventing-medicinal chemistry, since some clinical evidence shows the efficiency of peptide intake for improving hypertension disease. In Japan, evidencebased foods with health claim (FOSHU, or foods for specified health use) have been developed and accepted by the Japanese Ministry of Health, Labour and Welfare (http://www/mhlw.go.jp/). For FOSHU products effective for modulating BP in borderline hypertensives, seven products (tryptic hydrolysate of casein, Katsuobushi [dried bonito] oligopeptide, 43

44

Part 2 Functions of Biologically Active Proteins and Peptides

Table 4.1. Antihypertensive FOSHU products. Functional Ingredient

Active Peptide

Daily Intake

Tryptic hydrolysate of casein

Phe-Phe-Val-Ala-Pro-PhePro-Glu-Val-Phe-Gly-Lys Leu-Lys-Pro-Asn-Met Leu-Lys-Pro Ile-Tyr

20 g

Val-Pro-Pro Ile-Pro-Pro Val-Tyr

VPP equiv. : 2.53 mg IPP equiv. : 1.52 mg 4g

Katsuobushi (dried bonito) oligopeptide Aqueous extract from Mycoleptodo-noides aitchisonii Lactobacillus helveticus— fer-mented milk (sour milk) Sardine peptide a

1.5 g 1g

Reduc-tion of SBP/DBPa (mmHg)

Reference

4.6/6.6

Sekiya et al. 1992

11.7/6.9

Fujita et al. 2001

9.4/6.7

Tsuchida et al. 2001

12.5/6.2

Kajimoto et al. 2001

9.3/5.2

Kawasaki et al. 2000

SBP: systolic blood pressure; DBP: diastolic blood pressure.

aqueous extract from Mycoleptodonoide s aitchisonii, Lactobacillus helveticus-fermented milk [sour milk], sardine peptide, seaweed peptides, and sesame peptides) are available in the local market, most of which involve the inhibition of angiotensin I–converting enzyme (ACE) by small peptides (Table 4.1). The efficacy of peptide intake for borderline hypertensives is evidentially developed on the basis of extensive intervention trials, but such an effective FOSHU medication led us to a potential question of whether the antihypertensive effect of peptides is achieved only by ACE inhibition or suppression of the renin-angiotensin system, like therapeutic ACE inhibitory drugs.

2. Hypertension and the Renin-Angiotensin System Arterial BP regulation is mainly achieved by diverse metabolic systems: pressor and depressor hormonal systems and nerve systems (Sealey and Laragh 1990). Among these, the renin-angiotensin (-aldosterone) system is thought to be one of the predominant pressor systems, widely occurring in not only the circulatory blood system but also in diverse organs such as brain, lung, aorta, and kidney. In this system, angiotensinogen from the liver is primarily cleaved by renal renin to produce angiotensin (Ang) I that is a decapeptide. Ang I is then converted by the action of ACE (EC 3.4.15.1, dicarboxypepti-

dase) to potent vasoconstrictor Ang II by cleaving the dipeptide His-Leu from the C-terminal of Ang I. The major physiological role of Ang II is to exert a vasoconstrictive effect at the vessel wall via the binding of Ang II to Ang II receptor (AT1) (Millatta et al. 1999). Ang II also participates in the increment of extracellular fluid volume through a stimulation of adrenal aldosterone release, by which renal tubular sodium reabsorption is enhanced. Thus, it has been recognized that the circulatory reninangiotensin system plays a crucial role in the development and maintenance of hypertension. Updated research (Bader and Ganten 2008) also helps us to understand the importance of the local renin-angiotensin system in regulating BP promotion, where new candidates of (pro)renin and ACE2, an Ang (1-7) producing enzyme, involve the local (kidney, heart, vessel, or brain) BP regulation system like autocrine/paracrine hormone (Figure 4.1).

3. Design of ACE Inhibitory Peptides In order to prevent the pathogenesis of hypertension or to treat an elevated BP, suppression of Ang II production via inhibition of ACE activity would be of great benefit, because both renin-angiotensin and kinin-kallikrein systems involve ACE action. In addition, taking into consideration that ACE has four functional amino acid residues of Tyr, Arg, Glu, and Lys at the active site, and three hydrophobic

Chapter 4 Antihypertensive Peptides and Their Underlying Mechanisms

45

Renin-Angiotensin System (RAS) Prorenin

Angiotensinogen A i t i Renin

Angiotensin(1-9)

(Pro)renin receptor

Angiotensin I ACE2

ACE

ACE

Angiotensin(1-7)

Angiotensin II ACE2

Mas-R

AT2-R

Antihypertensive events

AT1-R

Hypertensive events

Figure 4.1. Updated circulatory renin-angiotensin system.

binding subsites, favorable blockade of ACE action would be achieved by small peptides or peptidic inhibitors having high affinity with active sites. The finding that the transporter-recognized di- and tripeptide length is expressed at the intestine (PepT1) (Minami et al. 1992; Vig et al. 2006) also allows us to investigate the possible functionality of small peptides after absorption. From this point of view, many ACE inhibitory peptides have been designed and identified from natural proteins (Matsui and Matsumoto 2006); as a therapeutic ACE inhibitory drug, captopril or enalapril, was designed on the basis of a basal structure of Ala-Pro or Phe-Ala-Pro, respectively (Hooper 1991). This is the reason why small peptides are targeted for developing antihypertensive food through ACE inhibitory action. ACE inhibitory peptides (>400) reported so far provide the evidence that small peptides with hydrophobic and aromatic amino acid residues such as Tyr, Phe, Trp, and Pro at the C-terminal have a potent ability to inhibit ACE activity with an IC50 value of < 100 μmol/L (Matsui and Matsumoto 2006). A successful human study was reported using sardine muscle hydrolysate by alkaline protease showing an ACE inhibitory power of IC50 value

of 0.018 mg-protein/mL. After a 4-week administration of the sardine hydrolysate (4 g/day) to 29 borderline hypertensive volunteers (systolic BP/ diastolic BP, peptide-drink: 146.4/90.5 mmHg; placebo: 145.5/92.3 mmHg), a significant BP reduction (systolic BP/diastolic BP: 9.3/5.2 mmHg) was observed in the peptide-drink group, whereas there was no BP change in the placebo group (Kawasaki et al. 2000). The human volunteer study provided some useful information on the BP-lowering effect of natural antihypertensive food: no rebound phenomena and no side effects, such as dry cough, which are often observed when ACE inhibitory drugs are taken. Therefore, these findings evidentially reveal that the intake of antihypertensive FOSHU products prepared from natural food resources is of great benefit for regulating or improving an elevated BP. It seems likely that FOSHU products containing ACE inhibitory peptides possess a similar extent of BP-lowering power (Table 4.1). Contrary to the prevalence, there was a substantially great difference in ACE inhibitory activity between therapeutic drug (e.g., captopril: IC50 = 0.021 μmol/L) and peptides (e.g., Leu-Arg-Pro: IC50, 0.27 μmol/L). Some reports (FitzGerald et al.

46

Part 2 Functions of Biologically Active Proteins and Peptides

Table 4.2. Reported antihypertensive peptides from natural proteins in spontaneously hypertensive rats.

Peptide

Source

Tyr-Pro Leu-Lys-Pro Ile-Pro-Pro Val-Tyr

αs1-casein Dried bonito β-casein Sardine muscle

IC50a (μmol/L) 720 0.32 5 26

Decrease in SBP(mmHg)/ dose(mg/kg) −32.1/101 −16/92 −28.3/0.33 −43.4/104

a

Concentration of inhibitor required to inhibit 50% of the ACE activity. 1 Yamamoto et al. 1999. 2 Fujita and Yoshikawa 1999. 3 Nakamura et al. 1995. 4 Matsui et al. 2004.

2004) have also revealed the controversies between in vivo antihypertensive effect and in vitro ACE inhibitory activity of peptides. As summarized in Table 4.2, there seems to be no relationship between the BP-lowering effect of a given ACE inhibitory peptide and its IC50 value. In this regard, it remains unclear whether the antihypertensive effect of ACE inhibitory peptides is elicited only due to ACE inhibition; and, as can be seen in the later sections, we will find the potential involvement of small peptides in local BP regulation systems.

4. Antihypertensive Mechanism of Small Peptides 4.1. Inhibition of the Renin-Angiotensin System by ACE Inhibitory Peptides Genetically defined Tsukuba-Hypertensive Mouse (THM) was used to demonstrate the antihypertensive mechanism of small peptides, in which the pathogenesis of hypertension is restrictively determined by an enhanced renin-angiotensin system induced by human renin and angiotensinogen genes. Therefore, a BP lowering of THM would refer to a suppression of enhanced human renin-angiotensin system. As a result, a single oral administration of Val-Tyr, a predominant ACE inhibitor in sardine hydrolysate to 11 weeks THM (0.1 mg/g), was proven to cause a long-lasting BP reduction up to 9

hours (systolic BP9h: 120.7 ± 2.3 mmHg) (Matsui et al. 2003). This preferable result demonstrates that the antihypertensive effect induced by ACE inhibitory peptides closely correlates with human reninangiotensin system. In contrast to these findings, there was no difference in plasma ACE activity between control and sample groups at 6 hours, while a transient inhibition was observed at 1 hour after the administration. A transient ACE inhibition of Val-Tyr was also observed in spontaneously hypertensive rats (SHR) and human studies (Kawasaki et al. 2000; Matsui et al. 2004). For ACE activity at diverse organs, a long-term suppression of ACE activity was observed in the kidney and aorta, while no change was observed in plasma ACE activity (Figure 4.2). These results suggested that both organs were targeting tissues of Val-Tyr. In other words, increasing plasma dipeptide has the power to suppress the pressor Ang II production via ACE inhibitory action transiently, but an alternative antihypertensive action occurring at the local tissues should be involved in the long-lasting BP-lowering effect of dipeptide. A similar long-lasting BP-lowering effect of ACE inhibitors was observed in an acute SHR administration study of spirapril as an ACE inhibitory drug (Okunishi et al. 1991) and 5-caffeoylquinic acid as an acetylcholine receptor mediator (Suzuki et al. 2002). A prolonged effect of the latter was reported to be due to slow metabolism of it to the candidate compound, ferulic acid, in the circulatory system. On the contrary, the effect induced by spirapril was reported to result from its long-lasting ACE inhibition at the aorta. Additionally, the finding that a young THM had already developed hypertension partly due to a remarkable vascular hypertrophy by excess vascular Ang II production led us to speculation that Val-Tyr or antihypertensive peptide might suppress an enhanced vascular renin-angiotensin system. The findings that (1) plasma Val-Tyr level at 1 hour was as little as in normotensives (12 mg dose of Val-Tyr: Cmax; 1.9 ± 0.1 pmol/mLplasma) (Matsui et al. 2002), much lower than that of captopril (Cmax at 25 mg dose; 603 pmol/mLplasma) (Jankowski et al. 1995), and (2) in vitro ACE inhibitory activity of Val-Tyr (IC50; 26 μmol/L)

Chapter 4 Antihypertensive Peptides and Their Underlying Mechanisms

47

Plasma 50 ACE activity (mU/mL plas sma)

% Reduction of SBP

0

40 30 20 10 0

##

0

1

-10

6

Time (h) ## ##

Aorta

##

-20

Kidney 5

1

3

6

Time after administration (h)

9

4

＊＊

＊＊

3 2

ACE activity A (mU/mg protein)

0

ACE activity A (mU U/mg protein)

5

4 3 2

1

1

0

0 0

1 Time (h)

6

0

＊

＊

1

6

Time (h)

Figure 4.2. Change in systolic blood pressure (A) and ACE activities (B) of 18-week-old spontaneously hypertensive rats after a single oral administration of 10 mg/kg Val-Tyr (䊉) or control (䊊). Each value is expressed as mean ± SEM (n = 5). ##p < 0.01 compared with the control group. *p < 0.05, **p < 0.01 compared with 0 hours.

was much weaker than that of captopril (IC50; 0.021 μmol/L), also suggest little contribution of plasma Val-Tyr increment to long-lasting BPlowering effect.

4.2. Regulation of Vascular Events by Dipeptides Antihypertensive peptide may play a potential role in regulating the vascular function, though the mechanism at the aorta remains unclear. Thus, our next trial was to demonstrate the latent function in the cell line experiment. Human vascular smooth muscle cell (VSMC) was used, since the aorta was reportedly one of the accumulated tissues of some ACE inhibitory peptides and directly responsible for vasoconstriction tone. In a VSMC proliferation experiment in 5% FBS-SmBM using Val-Tyr (IC50; 26 μmol/L),

Ile-Trp (IC50; 2.0 μmol/L), and Ile-Val-Tyr (IC50; 0.48 μmol/L), Val-Tyr was found to show a marked antiproliferation action in serum-stimulated VSMC growth (46% decrease in the cell number at 1 mmol/L Val-Tyr) (Matsui et al. 2005). Although Ile-Val-Tyr also caused a slight decrease in the growth to 82% of control, Ile-Trp was no longer an antiproliferative peptide, being provided a conflicting result with its ACE inhibitory potentials. Taking into consideration the signal-transduction pathway via AT1-receptor, an Ang II stimulation experiment was then conducted. In the presence of the peptides at a concentration of 1 mmol/L, a potent suppression of the WST-8 incorporation into Ang II–stimulated VSMC for Val-Tyr was observed, with a reduction to ca. 65% of the control (Figure 4.3). Captopril as well as Ile-Trp and Ile-Val-Tyr did not show any influence on the incorporation

48

Part 2 Functions of Biologically Active Proteins and Peptides

Bay K 8644-stimulation

200

200

180

180

160 140

＊＊

120 100 80 60 40 20

160 140 120

＊

＊＊

＊＊

100 80 60 40 20 0

0 Control Captopril

ACE inhibitory activity (µmol/L)

Incorporation (% of unstimu ulated)

Inco orporation (% % of unstimula ated)

Ang II-stimulation

Ile-Trp Ile-Val-Tyr Val-Tyr

2.0

0.48

Control Verapamil Val-Tyr

Paxillin

Paxillin + Val-Tyr

26

Figure 4.3. Effect of small peptides on angiotensin (Ang) II- or Bay K 8644-induced VSMC proliferation. VSMCs at a density of 1 × 104 cells/well were treated for 48 hours with 1 μmol/L Ang II in the presence of either 1 mmol/L peptides, 1 μmol/L captopril (ACE inhibitor), 1 μmol/L verapamil (Ca2+ channel inhibitor), or 1 μmol/L paxillin (K+ channel blocker). *p < 0.05 and **p < 0.01 compared with control by Tukey-Kramer’s t-test.

at a concentration of 1 μmol/L, which strongly suggested that the antiproliferative effect induced by Val-Tyr was not a result of aortic ACE inhibition. A similar suppression effect of the incorporation by Val-Tyr was observed, irrespective of the presence of AT1-receptor selective antagonist (losartan) or nonselective AT-receptor antagonist (saralasin) (see Matsui et al. 2005, indicating that Val-Tyr had no antagonistic effect against Ang II–related receptors). When Bay K 8644 acting as a mitogen through voltage-gated L-type Ca2+ channel stimulation was used, 1 mmol/L Val-Tyr significantly inhibited the increasing incorporation stimulated by 1 μmol/L Bay K 8644, like that which 1 μmol/L verapamil (therapeutic L-type Ca2+ channel blocker) inhibited (Figure 4.3). In contrast, the presence of paxillin (K+ channel blocker) did not affect the inhibition by Val-Tyr. This provided evidence that the antiproliferation by Val-Tyr would be in part due to inhibition of extracellular Ca2+ influx into VSMC by blocking voltage-gated L-type Ca2+ channel, not by stimulating K+ channel. So far, no study has been reported

on bioactive small peptides responsible for blocking voltage-gated L-type Ca2+ channel.

4.3. Relaxation of Vascular Constrictive Events by Dipeptides Either vascular constriction or relaxation closely relates with VSMC actions, which are critical for hypertension disease including vascular or arteriosclerotic lesions (Dzau 2001). VSMC proliferation, hypertrophy, or migration is induced by Ang II and/ or norepinepherine stimulation; among these Ang II that acts as an autocrine/paracrine mediator at the renin-angiotensin system plays a prominent role in the pathogenesis of vascular lesions via cell proliferation (Mehta and Griendling 2007). Thus, the application of dipeptides having voltage-gated L-type Ca2+ channel blocking action, like AT1receptor antagonist (Miura et al. 2003) or Ca2+ channel blocker (Stepien et al. 1997), for the treatment of vascular lesion-related diseases including hypertension would be highly appreciated.

Chapter 4 Antihypertensive Peptides and Their Underlying Mechanisms

p < 0.05

Consttrictive tens sion (% % of Controll)

140 120 100 80 60 40 20 0

Peptide (1 mmol/L) Control

Ile-Tyr

Tyr-Val

Val-Tyr

Val-Tyr

Figure 4.4. Vascular relaxation effect of 1 mmol/L Ile-Tyr, Tyr-Val, and Val-Tyr in 18-week-old SHR thoracic aorta rings constricted by 30 mmol/L KCl. Val-Tyr was subjected to endothelium-intact and –denuded vasoconstrictive experiments. EC: endothelium.

On the basis of the finding that Val-Tyr would be a Ca2+ channel blocker, an ex vivo vasoconstrictive experiment using rat aorta rings was primarily conducted. As a result, Val-Tyr exerted a significant vascular relaxation effect in SHR thoracic aorta rings in an endothelium- and ACE inhibition-independent manner (Figure 4.4) (Tanaka et al. 2006). The effective and beneficial effect of Val-Tyr in constricted aorta rings was also reported and demonstrated by Vercruysse et al. (2008). Regarding bioactive peptides with respect to vascular functions, some reports to date have investigated their vascular responses. Akpaffiong and Taylor (1998) reported on the effect of glutathione on relaxation of SHR aorta rings, in which the tetrapeptide potentiated acetylcholineinduced relaxation in an endothelium-dependent manner. However, the vascular relaxation through improving antioxidant systems may be restrictive to peptides with antioxidant activity like glutathione, but a possibility that other peptides are also involved in endothelium-dependent relaxation can be excluded. An interesting study on vascular responses of bioactive peptides was reported on dipeptide carnosine (beta-Ala-His) (Ririe et al. 2000), in which 1 mmol/L carnosine exerted ca. 10% relaxation effect in Sprague-Dawley (SD) rat aorta rings, com-

49

parable with the effect of 1 mmol/L Val-Tyr (Figure 4.4). The relaxation mechanism of carnosine was reported to be due to its suppression of cyclic GMP production in VSMC (Ririe et al. 2000), but any crucial role of carnosine in VSMC signaling pathways was not clarified. Peptides from ovalbumin, kappa-casein, egg white protein and rubisco were also reported to be a peptidic vasodilator: Ala-AspHis-Pro-Phe from ovalbumin (Matoba et al. 1999), Met-Ala-Ile-Pro-Pro-Lys-Lys from kappa-casein (Miguel et al. 2007a), and Lys-Ala-Asp-His-Pro and Tyr-Pro-Ile from egg white protein (Miguel et al. 2007b) were clarified as endothelium-dependent vasoactive peptides. Thus, it seems likely that peptides have an ability to regulate the vascular response, although the structural properties required for the effect remain unclear. To clarify the structure-vasoactivity relationship of peptides, a first attempt was performed using 62 synthetic di- and tripeptides in SD rat aorta rings (Tanaka et al. 2008). As summarized in Table 4.3, N-terminal amino acids of tryptophanyl dipeptides would make an important contribution to vasorelaxation action in thoracic aorta and would play an alternative crucial role in exerting a vasorelaxation effect. Among the screened peptides, Trp-His evoked the most potent vasorelaxation effect with an EC50 value of 3.4 mmol/L. As can be seen in Figure 4.5, Trp-His relaxed the 50 mmol/L KCl-constricted aorta rings in an endotheliumindependent manner, as Val-Tyr did. As mentioned above, carnosine had an endothelium-dependent vasorelaxation power, in which it stimulated the soluble guanylate cyclase/cyclic GMP relaxation pathways (Ririe et al. 2000). Arg-Ala-Asp-His-Pro from egg white proteins also acted as an endothelium-dependent vasodilator, through the stimulation of endothelial NO production pathways via B1 bradykinin receptor (Miguel et al. 2007b). In contrast to the endothelium-dependent vasorelaxation action of longer peptides, the endothelium-independent vasorelaxation action of Trp-His would be closely associated with some events in vascular smooth muscle layer, apart from endothelium signaling talks including the renin-angiotensin system. Interestingly, a competitive inhibition study with Ca2+ channel

50

Part 2 Functions of Biologically Active Proteins and Peptides

Table 4.3. Screening of vasorelaxant peptidesa of 50 mmol/L KCl-constricted aortic ring.1 Å@ X-Tyr X=

Val-X X= X-Phe X=

X-Trp X=

Peptidea

Relaxation (% of KCl Constriction)

Ala Phe Gly His Ile-Phe Ile-Leu Ile-Val Lys Leu-Ile Pro Ser Trp-Ile Trp Tyr-Ile Tyr-Val

Å—b Å— Å— Å— Å— Å— Å— Å— Å— Å— Å— Å— Å— 66,000

Rg (Å)

Daq(× 107 cm2/s)

4.3 — 4.7 18.6 13.2 15.2 16.3 22.9 30.7 46.5 —

21.8 (4.4) — 21.2 (–) — 7.0 (0.7) 5.4 (1.2) 5.3 (0.1) 3.6 (0.7) 3.5 (0.3) 2.4 (–) —

Source: Clogston and Caffrey 2005. Standard deviations are shown in parentheses.

a

aqueous channel (dw). Surprisingly, in the case of apo-ferritin with a diameter of 107 Å, entrapped in a cubic phase with dw = 73 Å, while the release was slow, it was observed (data not shown). The authors explained this contradiction on the basis that the cubic phase is a liquid crystal with inherent flexibility. The amplitude of this flexible motion, which amounts to a molecular breathing or peristalsis, is sufficient to create transient and random sections of channels that are large enough for the oversized additive to pass through. Assuming that transport is through the aqueous channels, probably the large molecule snakes its way through the channel network and eventually into the sink compartment (Clogston and Caffrey 2005). Another possible reason for retention, raised by Clogston and Caffrey (2005), concerns the fact that the cubic phase is composed of randomly oriented domains with a cubic symmetry. It is not clear what envelops each domain and what is at the interface between adjacent domains. If domains are considered to be surrounded by one or several continuous bilayers, then transfer between domains is expected to be very slow involving the breaching of at least one bilayer. Alternatively, if the domains are locally connected by a highly distorted “cubic phase” (e.g., sponge phase), transport between domains might be retarded by the unusual properties of the bilayer and/ or the aqueous channels.

The effect of the aqueous channel’s size on the rate of release was stressed by testing three monoacylglycerols—monoolein (labeled as 9.9 MAG), monopalmitolein (9.7 MAG), and monovaccenin (11.7 MAG)—producing Pn3m cubic phase with full hydration at 20°C. The 9.9, 11.7, and 9.7 MAG produced cubic phases under these conditions with channel diameters of 47, 66, and 60 Å, respectively. The impact of the water channels on the rate of transfer was more pronounced on the diffusion characteristics of a macromolecule whose size approached that of the channel. Biochemical enhancers are a novel approach to increasing skin permeability for transdermal drug delivery, and the use of pore-forming peptide to increase transdermal transport is limited to just a small number of studies (Chen et al. 2006). The following recent and novel study by Kim et al. provides insight into the mechanism by which magainin peptides increase skin permeability. Moreover, their revealed transdermal-pH dependence offers the opportunity to modulate or trigger transdermal delivery rates by increasing or decreasing pH (Kim et al. 2008). Magainin has a net charge up to +4 and binds to negatively charged lipid membranes by way of electrostatic interactions. Its secondary structure is not well defined in a neutral aqueous environment; however, it forms an α-helical structure when

Part 4 Recent Advances in Bioactive Peptide Analysis for Food Application

adsorbed onto a negatively charged membrane, such as the surface of a bacterium (Matsuzaki et al. 1997). Magainins can then self-assemble into transmembrane pores that make the cell membrane leaky and can also lead to cell lysis, particularly in bacterial cells. The size of pores formed by magainins in lipid bilayers is estimated to be approximately 1 nm in diameter (Matsuzaki et al. 1994; Matsuzaki 1998). It was shown that magainin alone had no effect on skin permeability, probably because the relatively large magainin molecule had difficulty penetrating throughout the stratum corneum to make continuous transdermal pathways. However, when delivered from a formulation including an anionic surfactant, N-lauroyl sarcosine (NLS), in a 50% ethanol–phosphate buffer saline (PBS) solution, skin permeability was increased and thereby magainin penetration throughout the SC was facilitated (Kim et al. 2007). This enhancement was accompanied by increased SC lipid fluidity, as shown through differential scanning calorimetry (DSC), infrared spectroscopy, and x-ray diffraction measurements (Kim et al. 2007). To investigate the role of interactions between magainin and a drug as it diffuses through magaininmediated pathways in the SC, Kim et al. have used two model drugs—fluorescein and granisetron (Figure 24.12, up and down, respectively)—which are of similar molecular weight but carry opposite charge and changed the magainin charge state by changing pH. Measurements of skin permeability to fluorescein over a pH range of 7.4–11, where the charge of the skin, NLS surfactant, and fluorescein remain strongly negative, were carried out. However, magainin has an isoelectric point at pH 10.5, such that magainin changes from a + 2 positive charge at pH 7.4 to a neutral charge at pH 10.5, and a negative charge at pH 11 (Skoog and Wichman 1986; Kim et al. 2008). Transdermal permeation of fluorescein after treatment with magainin and NLS was increased by a factor of 35 (i.e., from an average of 0.037 to 1.302 μg of fluorescein) at pH 7.4, as shown in Figure 24.13 (Kim et al. 2008). However, raising the pH and thereby reducing magainin’s charge progressively removed magainin’s enhancement until

HO

OH

O

O

O Me N N S

H N N O

Me

R

Figure 24.12. Chemical structures of (up) fluorescein and (down) granisetron (Kim et al. 2008).

Fluorescein enhancement ratio

374

40 30 20 10 0

7.4

8

9 pH

10

11

Figure 24.13. Enhancement of transdermal fluorescein delivery as a function of pH. Skin was pretreated with NLS (䊏) or magainin + NLS (䊐) in 50% ethanol. Enhancement ratio represents the increase in transdermal fluorescein transported across skin over 5 hours at various pH values compared to delivery under identical conditions using a formulation of fluorescein in PBS (Kim et al. 2008).

pH 11. It was suggested that a positively charged magainin facilitated transdermal transport of negatively charged fluorescein due to electrostatic attraction at pH 7.4, but with increasing pH, as the

Chapter 24 Controlled Release and Delivery Technology of Biologically Active Proteins and Peptides

attraction decreased, the skin permeability enhancement decreased as well. Additional insight into the flux data presented in Figure 24.13 was obtained using multiphoton excitation microscopy, at various pH values, by imaging the amount of fluorescein delivered into the skin. Consistent with the flux data, optical sections through the epidermis show that the smallest amount of fluorescein was seen in the skin at pH 10, when the magainin charge was almost neutralized (Figure 24.14B); a greater amount was seen at pH 7.4, when magainin carried a + 2 charge that attracted nega-

375

tively charged fluorescein (Figure 24.14A). Z-stack images showing cross-sectional views of the epidermis in Figure 24.14C and D provide similar, complimentary results (Kim et al. 2008). In addition, CD measurements demonstrated that pH did not change the secondary structure of magainin in solution; microscopy indicated that pH did not affect the magainin content in the SC; and FTIR showed that pH did not affect lipid order, except at the lowest pH. These data are consistent with the proposed hypothesis that electrostatic forces between magainin

(A)

(B)

0 μm

5 μm

10 μm

15 μm

20 μm

26 μm

30 μm

35 μm

40 μm

Depth below skin surface (C)

(D)

Figure 24.14. Penetration of fluorescein into human epidermis imaged by multiphoton microscopy. Skin was treated with magainin + NLS. Fluorescein was delivered to skin for 5 hours at (A and C) pH 7.4, (B and D) pH 10. (A and B) Optical sections were taken at 5 μm increments starting at the stratum corneum surface on the left and proceeding deeper on the right. Scale bar is 100 μm. (C and D) Cross-sectional images were reconstructed as z-stacks with the stratum corneum surface on top and deeper tissue below. Scale bar is 20 μm (Kim et al. 2008).

376

Part 4 Recent Advances in Bioactive Peptide Analysis for Food Application

peptides and drugs mediate drug transport across the skin. The authors suggested that these electrostatic interactions occur between magainin loaded into the SC and drug molecules diffusing through transport pathways created by the magainin. However, they do not believe that magainin and drug molecules bind and diffuse together through the SC for several reasons. First, magainins were added as a pretreatment and then removed from the donor compartment of the diffusion cell before fluorescein or granisetron was added. Thus, there was no opportunity for magainin-drug binding in the donor compartment. Second, magainin was shown to be localized in the stratum corneum (i.e., the upper 10 μm of skin), whereas fluorescein was shown to penetrate deeply across the epidermis (i.e., > 40 μm). Furthermore, fluorescein and granisetron were revealed to be diffused across the full epidermis and into the receiver compartment of the diffusion cell. Finally, fluorescein has a molecular weight of 332 Da, and magainin has a molecular weight of 2,504 Da. Thus, a fluorescein-magainin complex would have a molecular weight of at least 2,836 Da. Magainin’s large size precludes it from diffusing across skin to an appreciable extent; it can only penetrate and remain within SC lipid bilayers due to its special physico-chemical properties as a pore-forming peptide. Given the large size of a fluorescein-magainin complex, it is unlikely that such a large complex would readily cross the skin. The transdermal studies conducted to date are still lacking information concerning the mode of absorption and distribution in the skin. A study by Bender et al. aimed to investigate distribution of a hydrophilic fluorescent model drug sulphorhodamine B (SRB; Figure 24.15) by visualizing its uptake in full-thickness human skin using four delivery systems (Bender et al. 2008). The delivery vehicles applied were two bicontinuous lipid cubic systems consisting of either GMO or phytantriol (PT) and water. Water and a commercial ointment have been used as reference vehicles for comparison formulations with cubic internal structures to an emulsion with discrete micrometer-sized aggregates (ointment) and lack the internal order (water). The formulations were applied on full-thickness human

SO 3H

–

Et 2N

O3 S

O+

NET2

Figure 24.15. The chemical structure of sulphorhodamine B (Bender et al. 2008).

skin (during 24 hours) and thereafter were investigated using two-photon microscopy (TPM). Twophoton excitation is an outcome of a nonlinear excitation process through simultaneous absorption of two photons, implying that near infrared light (NIR) can be used for excitation of fluorophores with fluorescence in the visible range of light (Denk et al. 1990). Since the NIR wavelengths lie in the so-called “optical window” of biological tissue, TPM enables imaging of fluorophores much deeper into highly light scattering and light absorbing tissue compared to confocal laser scanning microscopy, with minimal photo-bleaching and phototoxic effects (Cahalan et al. 2002; Zipfel et al. 2003). The in vitro distribution of SRB that has been visualized at different depths in human skin using TPM is illustrated in Figure 24.16. Variations in distribution patterns were observed and evaluated for each vehicle as seen in Table 24.2. In general, the observed SRB fluorescence was located in the intercellular spaces, creating a characteristic fluorescent pattern of polygonal structures surrounding the cells with a diameter of 30–50 μm. At the skin surface, nucleated keratinocytes in SC were observed as thin transparent sheets. The observed fluorescence within the keratinocytes implies that SRB had penetrated into the cytoplasm of the cells but not into

Chapter 24 Controlled Release and Delivery Technology of Biologically Active Proteins and Peptides

377

A

B

C

D

Figure 24.16. Two-photon fluorescence images showing the lateral distribution of sulphorhodamine B after 24 hours of passive diffusion in human skin using (A) a water vehicle, (B) commercial ointment, (C) GMO cubic phase, and (D) phytantriol cubic phase. The image depths (from left to right) are 0, 4, 8, and 12 μm. Each image plane corresponds to an area of 323 × 323 μm (Bender et al. 2008).

the nuclei. TPM revealed that the fluorescence distribution was different when comparing the traditional commercial ointment and water with the bicontinuous cubic phases. In the case of cubic phases, SRB was found to be located mainly in

microfissures and in threadlike structures. It should be noted that in a former study by the authors, the cubic vehicles were superior to commercial ointment for topical drug delivery of hydrophilic substances in vivo (Bender et al. 2005). Thus they assumed that

378

Table 24.2. Summary of fluorescent features observed in two-photon microscopy images at various tissue depths of human skin exposed to sulphorhodamine B using different vehicles. Vehicle: Depth (micrometer) Desquamated cells at skin surface Vehicle visible at skin surface

Water 0–5

6–10

Ointment

11–20 21–30 >30

6–10

11–20 21–30

>30

0–5

6–10

11–20 21–30

Phytantriol cubic phase >30

0–5

15/15

15/15

6/15

0

0

11/15

14/15

15/15

Polygonal cells

14/15 15/15

13/15

Cell nuclei

13/15 15/15

13/15

0

Micro-fissures

9/15

9/15

9/15

7/15

0

0

0

0

Threadlike structures

0–5

Monoolein cubic phase

Source: Bender et al. 2008.

3/15

0

15/15 15/15

0

13/15 13/15

3/15

0

4/15 14/15 14/15

14/15

13/15

0

0

0

5/15

5/15

3/15

0

0

6/15

11/15

0

5/15

11/15

5/15

0

7/15 14/15 14/15

14/15

13/15

9/15

0

0

12/15 12/15

6/15

0

6–10

0

14/15 14/15

0

5/15

11–20 21–30

4/15

>30

0

0

5/15

3/15

12/15 15/15 15/15

15/15

13/15

11/15

6/15

0

0

0

12/15 12/15

Chapter 24 Controlled Release and Delivery Technology of Biologically Active Proteins and Peptides

the intercluster penetration pathway was preferable for delivery of hydrophilic compounds. The commercial ointment and cubic phases were found to reside in skin wrinkles due to high viscosity and water insolubility of the formulations. Cubic phases, known to co-exist with excess water, can therefore resist washing with water or PBS. Moreover, their rheological characterization has revealed elastic rather than viscous behavior (Engström et al. 1992). The microfissures reported in the present study were approximately 5 μm wide and had an irregular and entangled structure. The intercellular pathway seems to be predominant when using the water vehicle and ointment, while the intercluster pathway seems to dominate the skin absorption from the cubic phases. The microfissures were not visible when performing TPM of skin autofluorescence (Paoli et al. 2008); however, these structures were expected to be present as a microscopic clustering of keratinocytes in normal skin. The elastic lipid cubic phases seemed to be able to penetrate deep into these preexisting microfissures, giving rise to the observed fluorescence pattern. Even if the microfissures become narrower further into the skin, SRB fluorescence was detectable deeper than 30 μm in about 50% of the GMO cubic and approximately 70% of the PT cubic phases. Thus, this route contributed to a more efficient delivery of hydrophilic substances using the bicontinuous cubic samples as drug delivery vehicles. Another obvious difference that was obtained by the cubic formulations, compared to water, was the thin threadlike structures that presented down to a depth of approximately 10 μm in the former. The authors interpreted this pattern as arising from lateral diffusion of the formulation into the lipid matrix between the cell layers, which can be explained by an interaction between the lipid bilayers of the formulation and the cellular lipid matrix. The GMO cubic phase, compared to the PT cubic phase, penetrated the lipid matrix in a finer and more homogenously distributed fluorescence pattern, implying different lipid bilayers—lipid matrix interactions between the cubic phase and the skin. This may be due to the different chain mobility of the oleoyl chains (GMO) and the phytanyl chains (PT).

379

4. Conclusion With the advancement in technology and formulation knowledge, a number of approaches have been used to overcome the limitations regarding proteins and peptides. Various liquid crystalline– based delivery systems have been developed for the delivery of proteins and peptides. These delivery systems were found to be efficient in incorporating large quantities of protein and peptides and protecting them from physical and enzymatic degradation. Additionally the liquid crystalline–based systems could contain permeation enhancers for achieving improved bioavailability and were able to sustain and control their delivery. It was demonstrated that the properties of the liquid crystalline structures can be tuned to regulate the rate of drug release. Additionally the additive size and shape had an impact on the transport rates (Daq was directly correlated to the size of the additive). A novel approach to increase skin permeability for transdermal delivery utilizing pore-forming peptides was introduced. Furthermore, their revealed transdermal-pH dependence can provide the opportunity to modulate or trigger transdermal delivery rates by altering the pH values. A recent investigation regarding distribution of hydrophilic fluorescent model drugs in fullthickness human skin was demonstrated.

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Index

A A beta protein precursor, 88t AB192, 318 ABriPP, 88t ABTS, radical-scavenging property of peptides and colorimetric binding assays for, 35 ACC phosphorylation, satiety, high-protein diets and, 143 ACE blood pressure regulation and, 207, 228, 256–257 first competitive inhibitors to, 170 forms of, 211 inhibition by peptides in vitro, derived from fish proteins, 208, 211 in vivo, derived from fish proteins, 212–214 structure-activity correlations among different peptide inhibitors of, 212 wheat peptide, prevention of hypertension and inhibition of, 298–299 ACE homologue (ACEH), 211 ACE inhibition mechanism, 211–212 ACE inhibitors, 6 blood pressure regulation and, 169–170 prototypes of, 207 soy proteins as, 80 synthetic, side effects with, 208

ACE inhibitory activity, bitterness and, 348–349 ACE inhibitory peptides blood pressure regulation and, 174, 175 design of, 44–46 in egg white albumin, 256 evaluating antihypertensive activity of, in spontaneously hypertensive rats, 173 from fish proteins, 207–215, 208 inhibition of renin-angiotensin system by, 46–47 from natural sources, potency of, 208 preparation of, 171–173 enzymatic hydrolysis, 171 fermentation products, 171–173 Acesulfame K, 351 Acid hydrolysis, fish gelatin and, 205 Actin, in myofibrillar tissue proteins, 204 Actinobacillus actinomycetemcomitans, lactoferrin and, 186 Actinomucor elegans peptidases, nonbitter protein hydrolysates and, 350 Activated carbon, debittering protein hydrolysates and, 349 Activator protein-1, 19

Acute hyperammonemia, GABA and prevention of, 125 Acyl-CoA oxidase, soy protein feeding in rats and, 73 ADanPP, 88t Adenovirus lactoferrin’s effects against, 185, 186 Lfcin’s antiviral activity against, 192 Adibi, S. A., 265 Adipocytes, inflammatory responses and, 71 Adipokines, 70 Adiponectin, 70, 71, 76 Adipose tissue, metabolic syndrome and, 70 Adiposity, soy protein action on, proposed molecular mechanism, 73 Adiposity reduction, soy protein’s effect on, 71, 72t, 73–74, 77–78t Advanced glycation end products, 227 Aerobic organisms, biochemical antioxidants and, 16 Affinity peptidomics, 308, 308–309 AGEs. See Advanced glycation end products Aggregation, protein and peptide drug inactivation with, 365 Aggregation profiles, of Humulin, Regular Iletin I, and Regular Iletin II, 365 383

384

Index

Aging process antioxidant-prooxidant balance and, 30 protein carbonyl compounds and, 29, 30 Agouti related peptide, 143 Akahane, Y., 213t Akpaffiong, M. J., 49 Alamethicin, liquid crystalline phases and, 363 Alanine, sweet taste of, 343 Alaska pollack ACE inhibitory peptides derived from, 208, 210t antioxidant peptides from, 217t antioxidative activity in gelatin extracted from, 218 branched amino acids present in antioxidant peptides from, 216 products of proteolytic digestion of gelatin extracts from, 211 Albumin, 247, 250 water-soluble, 290 wheat, 291 Alcalase, 154 Alcalase hydrolysates, 275 Alcalase-hydrolyzed zein, antioxidant activity of, 216 Alcohol consumption, reactive oxygen species and, 16 Aldehyde interactions between amino acids, flavor ingredients and, 354 orthonasal perception of aroma intensity and, 354 Aleurone layer bran, 233 rice kernel, 234 Alkali extraction, of rice bran proteins, 236 Alkaline hydrolysis, fish gelatin and, 205 Allergen epitope identification, 106–107 B-cell epitope mapping, 107 T-cell epitope mapping, 106–107

Allergens, hidden, 107 Allergic response clinical symptoms related to, 102 to food antigens: two-phase mechanism, 103 intestine mucosal barrier and, 102–103 T cells and, 105 Allergies. See also Food allergy; Wheat allergy defined, 295 lactoferrin’s anti-inflammatory properties and, 187 wheat, 295–298 Almeida, M. S., 282, 283 Alpha-amylase inhibitors, families of, in wheat, 298 Alpha blockers, 169 Alpha-chymotrypsin, nonbitter protein hydrolysates and, 350 Alpha-cyclodextrin, bitterness masked with, 350 Alpha-helical class of proteins and peptides, 361 Alpha-lactalbumin in bovine colostrum and milk, 153t putative biological functions of, 151 whey proteins and, 156–157 Alpha-synuclein, 92, 93t ALPMHIR, 162 Aluko, R. E., 62, 275, 280 Alzheimer’s disease, 89, 90 advanced glycation end products and, 227 amyloid beta peptide and, 32 amyloid beta protein and, 91 amyloid deposits and, 89, 95 amyloidosis and, 7 excessive levels of calmodulin and, 55 free radical attacks and, 29 nitric oxide levels and, 56 peptidomics and, 319 Amarowicz, R., 217t Amber wheat, 290 Ameal S, 163t, 170, 171t

Amino acids. See also Free amino acids antioxidant, endogenous, 29 antioxidant behavior of peptides and, 216 in eggs, 248, 249 in fish gelatins, 206 in fish protein, 204 flavor ingredients interacting with, 352 plasma, as central satiety signals, 142–143 plethora of research on, 354 potent antioxidant activity with, 17 residues of antioxidant peptides and, 35 aromatic, 45 design of ACE inhibitory peptides and, 44–45 flaxseed protein-derived peptides and, 58 as metal-ion binders, 37 in rice bran proteins, 240t serum essential amino acid levels in peripheral blood vessel after ingestion of test beverages, 266 sulfur-containing, in cereal grain proteins, 234 taste-active, development of, 355 taste-active properties of, 343–344 primary taste characteristics of, 343–344 synergistic interactions affecting taste and flavor, 344 umami taste and, 342 Aminopeptidases, reducing bitterness of protein hydrolysates and, 350 AMP-Activated Protein Kinase (AMPK), 143 Amylase, rice bran protein extraction and, 236 Amylin, 91 Amyloid beta peptide, 32 Amyloid beta protein, 88–89, 91, 93t

Index

Amyloid formation diseases associated with, 7 inhibitors, 95 preventing, 92, 94–95 Amyloidogenic proteins and peptides, 7, 87–95, 93t amyloidogenicity of small peptides, 92 natural occurrences of, 90–92 alpha-synuclein, 92 amylin, 91 amyloid beta protein, 91 beta2-microglobulin, 90 cystatin C, 90–91 huntingtin protein, 92 prion, 90 strategies for preventing amyloid formation, 92, 94–95 peptidic compounds, 94–95 phenolic compounds, 92, 94 treharose, 95 Amyloidosis, 88, 95 cutaneous, 87 defined, 89–90 diseases associated with, 7 localized, 90 systemic, 87, 90 understanding molecular basis of, 89 Amyloids defined, 89–90 precursor and names of, 88t Anaphylaxis, allergic response and, 102 Anderson, G. H., 138., 141 Anderson, J. W., 74, 77t Ando, Y., 88t Angelova, A., 363 Angiogenesis, bLf and hLf’s opposite effects on, 189–190 Angiotensin I, 207, 257 Angiotensin I-converting enzyme, inhibitory effects of, 280–281 Angiotensin II, 207, 257 Ang I, 44 Ang II, 44 Ang II-stimulation, effect of small peptides on, 47, 48

Aniline-Benzoic Acid Labeling (AniBAL), 316 Animal feeds lactoperoxidase in, 160 rice bran proteins in, 239 Animal muscle-based bioactive peptides, 225–229 biological activity and therapeutic applications, 226–228 antiaging effects, 228 antiglycation effects, 227 antihypertensive and cardiovascular effects, 227–228 anti-inflammatory and immune-modulating activity, 227 antioxidative activity, 226 neurological effects, 228 wound healing, 228 description of, 225–226 future studies on, 228–229 Animal proteins, bioactive proteins released from, 332 Animals, role of GABA in, 124–125 Animal sources of foods, 105 ANS (8-anilino-1-naphthalene sulfonic acid), defined, pea protein-derived peptides and, 63 Anserine, 225 in animal muscle, 225 antioxidative activity of, 30, 31t, 226 in chicken meat, 226 dose-dependent ACE-inhibitory activities of, 228 neurological effects of, 228 Anterior piriform cortex, detection of high-protein meals and, 145 Antiaging effects, of muscle-based bioactive peptides, 228 Antiamyloid agents, development of, 7 Anticancer peptides, in egg protein, 255 Antidepressant agents, GABA receptors and, 124

385

Antigen-presenting cells, 103 Antihypertensive effects, foods with specified health use and, 170–171 Antihypertensive food products, development of, 6 Antihypertensive peptides, 8, 43–52, 169 antihypertensive mechanisms of small peptides, 46–51 inhibition of renin-angiotensin system by ACE inhibitory peptides, 46–47 regulation of vascular events by dipeptides, 47–48 relaxation of vascular constrictive events by dipeptides, 48–51 derivation of, from caseins by proteolytic action, 172t design of ACE inhibitory peptides, 44–46 docking of, into ACE C-terminal and validation of computational modeling with experimental inhibition of peptides, 81 in egg protein, 256–258 in FOSHU products, 44t, 171t future prospects, 51–52 hypertension and renin-angiotensin system, 44 mode of action ACE inhibitory effects, 174 peptide absorption, 174 reported, from natural proteins in spontaneously hypertensive rats, 46t screening of vasorelaxant peptides of 50 mmol/L KCI-constricted aortic ring, 50t in vivo effect, 173–174 clinical trials, 173–174 effects on an animal model, 173 Antihypertensive pharmaceutical products, categories of, 169

386

Index

Anti-inflammatory proteins and peptides, 19, 20t, 21–23 egg proteins lysozyme, 19, 20t ovotransferrin, 19, 20t milk peptides, 19, 20t, 21–22 bovine casein, 19, 20t, 21 glycomacropeptide-κcaseinoglycopeptides, 20t, 21 lactoferrin, 20t, 21–22 proteose peptone-3, 20t, 22 plant proteins/herbal medicine, 23 soy, 22–23 Antimicrobial proteins and peptides, 169 alpha-helical motifs for, 184 from chickpea (Cicer arietinum), 283 from cowpea (Vigna unguiculata), 282–283 in eggs, 249t from garden pea (Pisum sativum), 281–282 from lysozyme, 251–252 from ovalbumin, 252–253 from pea, commercial utilization potential of, 283–284 Antioxidant proteins and peptides, 16–17, 29–39 action mechanisms of, 35–38 chemical reactions, 35–37 physical reactions, 37–38 activity of, in food systems, 34–35 antioxidant activity of in vitro protein digests, 32–34 chemical and physical mechanisms of: metal chelation, radical scavenging, and physical hindrance, 35 dietary, identifying fate of, 6 in eggs, 255–256 endogenous, 30–32 enzymatic oxidation, 214–215 from fish proteins, 214–215, 217t human health promoted with, 30 mechanism of lipid oxidation, 214 preparation of, 38–39 chemical synthesis, 39 enzymatic production, 38 microbial fermentation, 38–39

structure-function relationship of, 35–36 Antioxidants natural, 215 synthetic, 215 Antioxidant supplements, expanding market for, 30 Antioxidative peptides, with less bitterness, 349 Antioxidative stress food factors, 16 Antioxidative stress mechanisms, endogenous, 16 Antioxidative stress proteins and peptides, 16, 17–18, 17t egg yolk peptides, 17–18 milk protein, 18 plant proteins/herbal medicines, 18 Antitumor activities, lactoferrin and, 189–191 Aoyama, T., 268 AP-1. See Activator protein-1 APCs. See Antigen-presenting cells Apolipo-protein AI, 88t, 93t Apolipo-protein AII, 88t Apolipo-protein AIV, 88t Apoptosis in cancerous cells, lactoferrin’s promotion of, 190 Apo serum AA, 88t Aptamers, 313 Aqueous alcholol-soluble prolamin, 290 Aqueous channel size, drug release rate and, 373 Arachidonic acid production, soy protein and, 76 Arcan, I., 274 Ardo, Y., 349 Area postrema, detection of high-protein meals and, 145 Arginine ACE inhibitory activity, bitterness and, 349 blood pressure and, 80 hypocholesterolemic effects of pea proteins and levels of, 277 Arietin, 283 Ariyoshi, Y., 209t

Aroma perception, research on chemosensory stimuli and, 354 Aromatic amino acids, 274 Arthritis colostrum-based products with growth factors and, 161 lactoferrin’s anti-inflammatory properties and, 187 Artificial sweeteners, 342, 351 Ascorbic acid, 215 Ash, in bran, 233 Ashar, M. N., 162 Asia, rice production in, 233 Asparagines, in rice bran proteins, 238 Aspartame, 351, 355 Aspartic acid, 37 Aspergillus niger, pea protesase inhibitors expressed with, 279 Astawan, M., 209t, 210t, 213t Atherosclerosis advanced glycation end products and, 227 free radical attacks and, 29 reactive oxygen metabolites and, 226 Atlantic cod, serine collagenases isolated from, 205 Atlantic salmon, ACE inhibitory peptides derived from, 210t Atrial natriuretic factor, 88t Atwater factor, for protein, 142 Autistic spectrum disorders, carnosine supplementation and, 228 Avian eggs, 247 Avian eggshell, unique mechanical properties of, 249 Avidin anticancer properties of, 255 antimicrobial properties of, 254 Azadbakht, L., 68 Azeotropic extraction, debittering protein hydrolysates and, 349 Aziz, A., 141 Azzout-Marniche, D., 142

Index

B Baby foods, rice bran proteins in, 239 Bacillus cereus, ovotransferrin’s effect against, 252 Bacillus stearothermophilus lactoferrin’s antimicrobial activities and, 185 lysozyme effective against, 250 Bacillus subtilis, lactoferrin’s antimicrobial activities and, 185 Bacteria, LfcinB and LfcinH actions against, 191 Bacterial adhesions, lactoferrin binding to, 186 Bacterial GAD, 122 Bacterial infections, lactoferrin and, 187 Bacteriocins, applications for, 240 Bacteriorhodopsin, 361 Badii, F., 206 Baker’s asthma, 295, 296, 299 Bakery products, rice bran proteins in, 239 Balenine, antioxidant activity and, 30, 31t Balog, C. I., 318 Barley, rice protein net protein utilization compared to, 240 Baron, F., 249t Bar-Or, D., 37t Basmati rice, 237 Bassil, M. S., 143 BAT. See Brown adipose tissue Baumann, M., 88t Bay K 8644-stimulation, effect of small peptides on, 48, 48 BBIs. See Bowman-Birk protease inhibitors B-cell epitope-based immunotherapy (IgG-binding), food allergy and, 110 B-cell epitopes antigen, representation of, 106 food allergen, 105–106 mapping, 107

Beard, rice kernel, 234 Beef allergy model, 114 Beef gelatin, producing gelatin from fish to match gelling properties of, 219 Beer production, lysozyme used in, 251 Behavior, peptides and regulation of, 320 Bellamy, W., 183 Bender, J., 376 Benditt, E. P., 88t Beni-koji making, GABA content and, 126 Bensaid, A., 144 Benson, M. D., 88t Bergstrom, J., 88t Bertenshaw, E. J., 136 Berthoud, H. R., 144 Beta blockers, 169 Beta-carotene, 215 Beta cellulin, in bovine mammary secretions, 152, 160–161 Beta-conglycinin, 17 Beta-glucans, 233 Beta-hydroxyacyl-CoA dehydrogenase, soy protein feeding in rats and, 73 Beta-immunoglobulin peptide, health benefits with, 162 Beta-lactoglobulin antioxidant activity and, 34 in bovine colostrum and milk, 153t putative biological functions of, 151 whey proteins and, 157 Beta-lactorphin, health benefits with, 162 Beta-lactosin B peptide, antihypertensive activity with, 162 Beta-sheet class of proteins and peptides, 361 Beta2-microglobulin, 88t, 90, 93t BHA. See Butylated hydroxyanisole BHT. See Butylated hydroxytoluene Bicontinuous cubic phase medium, 363 Bicuculline, 125

387

Bigeye snapper skin, autolysis of, by indigenous serine proteinases, 205 Binding unit, 347 Bioactive fragments, release of, in silico by trypsin from milk proteins, 334, 336 Bioactive peptides classification of, 307 defined, 154 enzymatic release of, from precursor proteins in silico, 335–336t examples of commercial dairy products and ingredients based on, 163t future research areas about, 163 in health: overview, 5–11 health benefits with, 162 in silico analysis of, 10, 326–328, 331 milk proteins and, 8, 152 novel applications of, 161–162 plant proteins and, 332, 334 production of, 154–155 release of, from selected precursor proteins, 154 by enzymes–proteolysis in silico, 331–332, 334 strategy for research on, 327, 327 for therapeutic purposes, 326 Bioactive peptides and proteins, from lactoferrin, 8 Bioactive properties, potential correlation between bitterness of peptides and, 348–349 Bioactive whey proteins, occurrence and isolation of, 152–154 Biochemical enhancers, skin permeability for transdermal drug delivery and, 373 Biochemistry, bioinformatics methods applied in, 10 Biofilm development of bacteria, blocking, lactoferrin and, 158 Bioinformatics methods applications of, 10 increasing popularity of, 339

388

Index

Biomarkers defined, 317 peptides as, 317–318 BIOPEP database of proteins and bioactive peptides comprehensive analysis of proteins as source of bioactive peptides by, 331 development of, 10 proteolysis simulation example in, 333 proteolytic enzymes of gastrointestinal system in, 332 structure and function of, 326 Biopeptides, identification of selected, released by trypsin from milk proteins, 334, 336 Biopharmaceuticals, emergence of, 359 BioPURE-GMP, 163t Bioseparation techniques, immune milk preparations and, 156 Biotechnology, bioinformatics methods applied in, 10 BioZate, 163t Bitterness of peptides potential correlation between bioactive properties and, 348–349 predicting, 347–348 of protein hydrolysates and peptides, physico-chemical properties related to, 345, 347 Bitter peptides, of proteins and protein hydrolysates, isolated by different researchers, 346–347t Bitter substances, 342–343 Bitter taste human response to, 342 protein hydrolysis and, 345 Blackeyed peas (Vigna unguiculata), Bowman-Birk protease inhibitors and, 279 Black tea, GABA content in, 125 Blake, C., 89

bLf. See Bovine-milk derived lactoferrin Blom, W. A., 136 Blood glucose levels, insulin study in nonagitated and agitated cubic phase and effect on, 366 Blood pressure. See also Antihypertensive peptides; Hypertension antihypertensive peptides and, 8 regulation of ACE inhibitors and, 169–170, 174, 175, 207, 256–257 renin-angiotensin system and, 298 soy protein and, 79–80 Bloom gelatin, 205 Bloom value, hydrophobic amino acids and, 206 Blue whiting, ACE inhibitory peptides derived from, 210t Blundell, J. E., 143 BMI. See Body mass index Body composition, sustained high-protein diet and, 136 Body mass index, soy consumption and, 71 Body weight, gamma-aminobutyric acid and, 125 Boldyrev, A., 31t Bolton, D. C., 88t Bonito ACE inhibitory peptides derived from, 208, 210t hypotensive effects of, in spontaneously hypertensive rats, 213t Bonito bowels, ACE inhibitory peptides derived from, 209t Borderline hypertension, most beneficial improvement for, 43 Bothrops jararaca, bioactive peptides isolated from, 170 Bougatef, A., 217t Bovine κ-casein, anti-inflammatory properties of, 19, 20t, 21

Bovine caseins calmodulin-binding peptides isolated from peptic hydrolysate of, and potency against phosphodiesterase I, 57t functional peptides in, 171 Bovine CGP, anti-inflammatory properties of, 21 Bovine colostrum major bioactive whey proteins in, 153, 153t natural antibodies in, 156 Bovine lactalbumin alpha chromatograms of, 336, 338 mass spectrum of tryptic hydrolysate of, 338 profile of potential biological activity of, 337 Bovine lactoferrin, apoptosis-related gene expression changes and, 190 Bovine Lfcin (LfcinB) structure of, 184 structure of: LfcinB domain and LfcinB peptide, 184 Bovine mammary secretions, growth factors in, 152–153 Bovine-milk derived lactoferrin angiogenesis and, 189–190 anti-inflammatory activity associated with, 22 antimetastatic effects with, 189 sequences of Lfcin and Lfampin peptides from, 184t systemic host immunity promoted with, 189 Bovine spongiform encephalopathies, 89, 90 amyloid deposits and, 95 amyloidosis and, 7 demand for fish gelatin and, 205 Bowen, J., 140, 141 Bowm, A. W., 123 Bowman-Birk protease inhibitors anticancer effects due to, 278–280 inhibitory mechanism of, 229 Bowman-Birk trypsin inhibitor, 20t, 22, 23 BP. See Blood pressure

Index

Bradykinin, blood pressure regulation and, 207 Brain senescence, GABA and prevention of, 124–125 Bram, rice kernel, 234 Bran, components of, 233 Bray, T. M., 31t Brazzein, 351 Bread antioxidant caseinophosphopeptides in, 35 GABA used in, 129 Brockmann, A., 320 Brown adipose tissue, soy peptides and, 267–268 BTC. See Beta cellulin Buccal delivery, oleic acid and membrane permeation in, 370 Buee, L., 88t Buforin II, 192 Bull, rice kernel, 234 Burton-Freeman, B. M., 160 Butter fat, inhibiting oxidation of, 216 Butylated hydroxyanisole, 36, 215 Butylated hydroxytoluene, 214, 215 Butylhydroquinone, 215 Byun, H. G., 210t C Cabral, K. M. S., 283 Caffeine, 342 Caffrey, M., 361, 372, 373 Calbet, J. A., 141 Calcitonin, 93t, 319 Calcium binding, calmodulin activation and, 55 Calcium channel antagonists, 169 Calkins, E., 89 Calmodulin (CaM) effect of flaxseed protein-derived peptides on intrinsic fluorescence of, 61t effect of flaxseed protein-derived peptides on secondary structure fractions of, 61t functions of, 55 role of, 6

Calmodulin inhibitors flaxseed protein-derived peptides, 58–62 food protein-derived peptides, 55–64 milk protein-derived peptides, 56–58 pea protein-derived peptides, 62–64 Caloric intake, soy protein and reduction in, 73, 74 Calpis, 162, 163t CaM. See Calmodulin CaM-dependent peptides, current stage of knowledge about, 64 CAM-dependent protein kinase II (CAMKII), 56 cAMP. See Cyclic adenosine monophosphate Campbell, B., 156 CaM-PDE inhibition of, 56 milk protein-derived peptides and, 56–58 Cancer chronic inflammation and, 227 excessive levels of calmodulin and, 55 free radical attacks and, 29 lactoferrin’s anti-inflammatory properties and, 187 lactoferrin’s biological roles in, 189–191 peptidomics and, 319 prevalence of and mortality rates with, 255 rice bran proteins and prevention/ control of, 241 Candida albicans immune milk preparations and, 156 lactoferrin’s antimicrobial activity and, 158 lactoferrin’s effects against, 185, 193 LfambinB peptide’s activity against, 193 Lfcin and inhibiting growth of, 192

389

Candida glabrata, lactoferrin’s efficiency against, 193 Candida spp., lactoferrin’s effect on, 187 Capelin antioxidant peptides from, 217t antioxidative activity of protein hydrolysates from, 218 Captopril, 47, 174 antihypertensive effects of, in spontaneously hypertensive rat, 173 zinc deficiency effects of, 208 Carbohydrates, 105, 342 Carboxypeptidases, reducing bitterness of protein hydrolysates and, 350 Carcinoembryonic antigen, 319 Cardiac hypertrophy, excessive levels of calmodulin and, 55 Cardiovascular disease fat dysfunction and, 71 hypertension and, 169, 207 Carloric sweeteners, 351 Carnitine palmitoyltransferase, soy protein feeding in rats and, 73 Carnosine in animal meat, 225, 226 antiaging effects of, 228 antiglycation effects of, 227 anti-inflammatory and immune-modulating activity of, 227 antioxidant activity and, 30–31, 31t, 226 chemical structure of, 31 dose-dependent ACE-inhibitory activities of, 228 hypotensive effect of, 227–228 neurological effects of, 228 wound healing effects of, 228 Carnosine relaxation effect, in Sprague-Dawley (SD) rat aorta rings, 49 Caryopsis, 233 Casein hydrolysates ACE-inhibitory activity with, 154 bioactive peptides and, 162

390

Index

Casein peptides, importance of helix structure configuration of, and effective binding to CaM, 58 Caseins antihypertensive peptides derived from, by proteolytic action, 172t antioxidant activity of peptides in, 34 functional properties of rice bran proteins and, 237 increase in GLP-1 concentrations in whey proteins vs., 141 Caspase-3, lactoferrin and, 190 Catalase (CAT), aerobic organisms and, 16 Cataracts, advanced glycation end products and, 227 Cathepsin G, 23 CCK. See Cholecystokinin CCK1 receptor, 140 CD4 antigen, lactoferrin and, 188 CD4+ T cells, food allergy and, 103 CD spectra. See Circular dichroism spectra CEA. See Carcinoembryonic antigen Cefaclor, 140 Celiac disease, 10, 114, 295, 297, 299 Cell migration, lactoferrin and, 188 Cell-permeable peptides, 192 Cell proliferation, lactoferrin’s biological roles in, 189–191 Cell signaling mechanisms, inflammation and, 19 Cellular homeostasis, histidyl dipeptides and, 225 Cellulose, 233 Central nervous system, mammalian, GABA and, 121 Central neuronal pathways, protein-induced satiety and, 143–144 Centripetal obesity, metabolic syndrome and, 67 Cereals antioxidant caseinophosphopeptides in, 35 natural antioxidants in, 215

proteins in, 234 world wheat production and, 9 worldwide production of, 233 Cerebral ischemia, oxidative stress and, 31–32 Ceruloplasmin, lactoferrin and, 183 Cetyltrimethylammonium bromide, hydrophobicity of insoluble glutelins and, 235 Chand, R., 162 Chaotropic solutes, properties of liquid crystalline phases and, 362, 363 Chapatti (flat bread), rice bran proteins in, 239 Charter, E. A., 249t Chatterton, D. E. W., 157 Cheese, bioactive peptides and, 161 Cheese ripening, GABA levels in, 126 Cheese starter bacteria, bioactive peptide production and, 155 Cheese whey beta cellulin in, 152 large-scale preparation of bLf from, 193 Cheison, S. C., 38 Chelikani, P. K., 140 Chemically Linked Peptides on Scaffolds, 107 Chen, H. M., 36, 37t Chen, K. M., 216 Chewing gum, bLf added to, 193 Chickpea (Cicer arietinum), 9, 273, 274 antimicrobial peptides/proteins and, 283 antioxidant effects of, 274–275 effects of proteolytic treatments on physicochemical and bitterness properties of, 275 future prospects for biological activities related to, 284 hypocholesterolemic effects and, 276 Chickpea protein hydrolysates effect of, on serum antioxidant activity of aged mice, 275t fractions from (Fra. I, Fra. II, Fra. III, Fra. IV), 274

China, wheat production and consumption in, 9, 289 Chocolate antioxidant caseinophosphopeptides in, 35 GABA in, 129 Cholecystokinin dose-dependence of, in protein-induced satiety, 140 food intake regulation and, 139, 140 protein and, 74 protein-induced satiety and, 138, 145 putative satiety mechanisms diagram, 139 soy protein and, 76 Cholesterol-rich diets, hyper-hypo-response phenomenon and, 277 Chondroitin sulphate, 186 Chromatograms, of bovine lactalbumin alpha, 336, 338 Chromatographic separation technique debittering protein hydrolysates and, 349 for fractionation and isolation of bioactive milk proteins, 153 Chronic disease bioactive peptides and proteins and, 5 CaM-dependent peptides and, 64 oxidative stress and inflammation and, 23 Chu, K. T., 283 Chuang, W. L., 217t Chum salmon, antioxidant peptides from, 217t Chun, H., 266 Chymase, 23 Chymotrypsin, 21, 154, 171 in BIOPEP database, 332 Bowman-Birk inhibitors and, 278, 278t Cicerarian, 283 Cicerin, 283 CIR. See Cosmetic Ingredient Review

Index

Circadian rhythm regulation, N-acetyl-5methoxytryptamine and, 31 Circular dichroic (CD) spectroscopy, of insulin in liquid crystalline system, 366, 367 Circular dichroism spectra, 361 CLA. See Conjugated linoleic acid Clark, A., 88t Class intervals, 328 Clemente, A., 279 CLIPS. See Chemically Linked Peptides on Scaffolds Clogston, J., 372, 373 Closed-interface domains, phenolic compounds and, 92–93, 93 Clostridium difficile enterotoxins, immune milk preparations and, 156 Clostridium perfringens, lactoferrin’s antimicrobial activity and, 158 Clostridium thermosaccharolyticum, lysozyme effective against, 250 Clostridium tyrobutyricum, lysozyme effective against, 250, 251 Clostripaine, 332 Codex Alimentarius Committee, 159 Coenzyme Q10, in animal muscle, 225 Cohen, A. S., 89 Cohen, D. H., 88t Coho salmon, ACE inhibitory peptides derived from, 210t Cola, GABA used in, 129 Colitis, anti-inflammatory effect of GMP and TNBS models of, in rats, 21 Collagen in connective tissue proteins, 204 hydroxyproline in, 204 Collagenase, 205, 332 Collagen triple helix structure, fish gelatin and, 205, 206 Colon carcinomas, Lfcin’s antitumor effects against, 192–193 Colostral immunoglobulins, biological function of, 156

Colostrum beta cellulin in, 152 growth factors in, 160–161 health-promoting proteins and peptides in, 7–8 immunoglobulins in, 152 natural antibodies in, 156 Combinatorial peptidomics, 308, 309 Conditioned taste aversion, 144 Conjugated linoleic acid, in animal muscle, 225 Connective tissue proteins, in fish proteins, 204 Controlled release of biologically active proteins and peptides, molecular and transport characteristics in bulk aqueous medium of additive molecules, 373t Convulsions, nitric oxide levels and, 56 COOH-terminal dipeptide residue, substrate specificity of ACE and, 212 Cookies, rice bran proteins in, 239 Cope, W. B., 74 Copper, 215 Coprinus comatus, sativin’s antifungal activity against, 282 Corn, rice protein net protein utilization compared to, 240 Cornish, J., 158 Corn oil, inhibiting oxidation of, 216 Corn protein, antioxidant acitivty of peptides in, 34 Cos, M. L., 74 Cosmetic Ingredient Review, 242 Cosmetics, bLf added to, 193 Costa, P. P., 88t Cota, D., 143 Cowpea (Vigna unguiculata), 9, 273, 274 antimicrobial peptides/proteins and, 282–283 future prospects for biological activities related to, 284 hypocholesterolemic effects and, 276

391

Cow’s milk allergy model, 112–113 COX-2. See Cyclo-oxygenase-2 CPK levels. See Creatine phosphokinase levels Cp-thionin II, bactericidal activity of, 283 Craft, I. L., 265 Creatine, in animal muscle, 225 Creatine phosphokinase changes in, after beverage ingestion: comparison of placebo, soy protein, and soy peptide on GH and CPK level, 268 soy peptides in sports and levels of, 267 Creutzfeldt-Jakob disease, 90 Crohn’s disease colostrum-based products with growth factors and, 161 fecal lactoferrin and, 194 “Cross-beta” conformation, 89 Cryptosporidium parvum, immune milk preparations and, 156 CS. See Chondroitin sulphate CTA. See Conditioned taste aversion C-terminal glutamate residue, for some inhibitory peptides, 212 CTLs. See Cytotoxic T lymphocytes Cubic phase delivery of proteins and peptides in, 360, 363 drug release rate and, 372 GMO, two-photon fluorescence images showing lateral distribution of sulphorhodamine B, after 24 hours of passive diffusion in skin and, 377, 377, 379 gramicidin D ‘s destinations within, 361 insulin and optical density of, 366 microfissures, SRB fluorescence and, 379 time course of in vitro skin penetration and percutaneous delivery of cyclosporin A incorporated in, 369–370, 370

392

Index

Cubic phase (continued) in vivo skin penetration of CysA incorporated into, compared to olive oil formulation, 371, 371 Cubic phase domains, drug release rate and, 373 Cubosome particles, 363 Cui, M., 351 Curculin. See Neoculin Curcumin, 16, 92 CVD. See Cardiovascular disease Cyclamate, 351 Cyclic adenosine monophosphate, 56 Cyclo (His-Pro), antioxidant activity and, 31 Cyclo-oxygenase-2, 18 Cyclosporin A (CysA) penetration experiments with liposomes with ethanol and, 371 time course of in vitro skin penetration and percutaneous delivery of, incorporated in cubic and hexagonal liquid crystalline phases, with olive oil control, 369–370, 370 in vitro penetration of, in stratum corneum and [E + D] at 6 and 12 hours following its topical application using hexagonal phase nanodispersion or olive oil control, 372 in vivo skin penetration of, incorporated in cubic and hexagonal liquid crystalline phases, compared to olive oil control formulation, 371, 371 Cystatin anticancer property of, 255 in egg, antimicrobial properties of, 254 as serine protease inhibitor, 258 Cystatin C, 88t, 90–91, 92, 93t Cysteine, 29, 274, 343 in cereal grain proteins, 234 radical quenching activity of peptides and, 35

Cystine, in cereal grain proteins, 234 Cytochrome C, liquid crystalline phases and, 363 Cytokine environment, food allergy and, 103 Cytokines, 307 Cytomegalovirus, 192 lactoferrin’s antimicrobial activity and, 158 lactoferrin’s effects against, 185 Cytotoxic T lymphocytes, food allergy and, 103 D Daddaoua, A., 20t Dahi, bioactive peptides and, 161, 162 Dairy products, novel applications of bioactive peptides and, 161–162 DC-SIGN receptor, lactoferrin binding and, 186 Debitrase, 350 Debittering approaches, for protein hydrolysates, 349–351 Decker, E. M., 216 Defatted (DF) bran, protein extraction from, 236 De Freitas, S. M., 229 Degree of milling, 233, 234 Dehydrin proteins, functional properties of, 237 Deibert, P., 77t Delacourte, A., 88t Delivery technology for biologically active proteins and peptides, 359–379 barriers and mechanism of bioavailability of proteins and peptides, 366–3709 entrapment and stability of proteins and peptides by liquid crystalline systems, 360–366 overview of difficulties related to, 359–360 prerequisites for success in, 360 Denatonium, 342 Denaturation, protein and peptide drug inactivation with, 365

Deng, S. G., 350 Dental health care products, lactoperoxidase in, 160 Dermatophytes, Lfcin and inhibiting growth of, 192 “Desensitization” induction, food allergy and, 108 Dextran sodium sulfate, 18 DF. See Diafiltration Dia, V. P., 20t, 23 Diabetes advanced glycation end products and, 227 chronic inflammation and, 227 cyclo (His-Pro) and amelioration of, 31 flavor-active components and novel therapeutic approaches to, 355 metabolic syndrome and, 67 overconsumption of salty and sweet foods and, 342 reactive oxygen metabolites and, 226 sodium substitutes and, 345 sweet proteins and, 351 wheat albumin and prevention of, 298 Diabetes mellitus, defined, 298 Diafiltration, manufacture of whey powder and whey protein concentrates and, 153–154 Dialysis-related amyloidosis, beta2-microglobulin and, 90 Diepvens, K., 139 Diet high-protein, satiety and food intake inhibition in, 137–138 high-protein meals, satiety and, 136–137 improvement in hypertension and, 43 therapeutic, metabolic syndrome and, 67, 68 Dietary antioxidant supplements, expanding market for, 30 Dietary Approaches to Stop Hypertension (DASH) diet, 68

Index

Diet-disease associations, peptides and, 319–320 Digestion process, antioxidant peptides and, 32–34 Di-glycerine peptides, absorption of, 265 Dilute acid- or alkali-soluble glutelin, 290 Dimeric domain-swapped L68Q human cystatin C, open-interface and closed-interface, 92, 94 Dioleoyl phosphatidylcholine vesicles, 361 Dipeptide ACE inhibitors, 212 Dipeptides development of, from soy, 266 intestinal adsorption of, 174 relaxation of vascular constrictive events by, 48–51 release of, from milk proteins, 332 salty taste and, 345 Disaccharides, polyglutamine aggregate formation and, 95 Disease lipid oxidation and, 214 oxidation and, 29 peptide biomarkers in, 319 Diuretic agents, 169 Doan, F. J., 30 DOM. See Degree of milling Domains of cubic structures, bicontinuous cubic phase medium and, 363 DOPC vesicles. See Dioleoyl phosphatidylcholine vesicles Douchi, antioxidant peptides in, 38 DPPH antioxidant effects from peas and, 274 radical-scavenging property of peptides and colorimetric binding assays for, 35 Drug penetration enhancement of, 368 hydrophilic and lipophilic pathways of, and mode of action of penetration enhancers, 368, 369

routes across the stratum corneum, 368 Drug release rate, properties of liquid crystalline structures and, 372, 379 Dry extrusion, rice bran stabilization and, 235 DSS. See Dextran sodium sulfate D3 protease antihypertensive effect of, 350–351 less bitter protein hydrolysates and, 350 Dunshea, F. R., 74 Dyslipidemia, 67, 71 Dziuba, J., 332, 339 E EAI. See Emulsion activity index Edible films, lactoferrin and, 194 “Edible vaccines,” 115 EDTA. See Ethylene di-amine tetra acetic acid EGF. See Epidermal growth factor Egg allergy model, 113–114 Egg proteins, 215 antioxidant activity of peptides in, 34 bioactive, recent advances in, 9 digestibility of, 248 Eggs anticancer proteins and peptides in, 255 antihypertensive peptides in, 256–258 antimicrobial proteins and peptides from, 249–254 avidin, 254 cystatin, 254 lysozyme, 250–252 ovalbumin, 252–253 ovomacroglobulin, 253 ovomucin, 253 ovotransferrin, 252 phosvitin, 253–254 antimicrobial proteins in, 249t antioxidant proteins and peptides in, 17, 17t, 255–256 components of, 247 fried vs. boiled, ACE inhibitory activities and, 257

393

immunomodulating proteins and peptides in, 254–255 major chemical compositions of different parts of, 248t as “nature’s perfect food,” 258 protease inhibitors in, 258 proteins in, 258 Eggshell, 249 Egg white, 247 biological functions of proteins in, 247–248 protease inhibitors in, 258 Egg yolk peptides, phosvitin phosphopeptides, 17–18, 17t Eimeria stiedai lactoferrin’s effects against, 186 Lfcin’s effects on, 192 Elastase, 23, 332 Electron spin resonance microscopy, radicals detected with, 35 Elicitation phase, in allergic response to food antigens, 103 Elimination diets, food allergy and, limits with, 107–108 Embryo, 233 Emulsion activity index, 236 Emulsion stability index, 236 Enalapril, 208 Enari, H., 210t Endocytosis, 102 Endogenous antioxidant peptides, 30–32 anserine, 30, 31t balenine, 30, 31t carnosine, 30–31, 31t cyclo (His-Pro), 31 glutathione, 30, 31t melatonin, 31, 31t SS31 peptide, 31, 31t Endogenous antioxidative stress mechanisms, 16 Endopeptidases, 317 Endosperm, 233 Endothelial isozyme, of NOS (eNOS), 56 Endothelial NOS protein molecule, CaM-dependent, effect of flaxseed protein-derived peptides on, 59–60

394

Index

Endothelin antagonist, 169 Energy balance, proposed model for role of mTOR signaling in hypothalamic regulation of, 144 Energy expenditure, as metabolic signal in protein-induced satiety, 142 Energy intake, regulation of, 7, 135 Enrichment bioactive milk proteins and, 153 immune milk preparations and, 156 Entamoeba histolytica, lactoferrin’s effects against, 185 Enterococcus spp., lactoferrin’s antimicrobial activities and, 185 Environmental factors, antioxidant-prooxidant balance and, 30 Enzymatic digestion, antioxidant peptides and, 38 Enzymatic extraction, of rice bran proteins, 236 Enzymatic hydrolysis, 171 Enzymatic oxidation, 214–215 Enzymatic treatment, for reducing bitterness of protein hydrolysates, 350 Enzymes, in bran, 233 Epidermal growth factor, in bovine mammary secretions, 152, 161 Epidermis, penetration of fluorescein into, as imaged by multiphoton microscopy, 375 Epitalon, 31 Epithalamin, 31 Ericsson, B., 366 Escherichia coli GABA biosynthesis with, 126 immune milk preparations and, 156 lactoferrin’s antimicrobial activities and, 158, 185, 186 lysozyme and, 250 Escherichia coli K-12, ovotransferrin’s effect against, 252

ESI. See Emulsion stability index ESR microscopy. See Electron spin resonance microscopy ESR spectrum, gel filtration of whey protein and, for OH signals of samples containing different peptide fractions, 36 Essential hypertension, most beneficial improvement for, 43 Ethanol-phosphate buffer saline solution, skin permeability study and, 374 Ethoxyquin, 214 Ethylene di-amine tetra acetic acid, 250 EU. See European Union Eulitz, M., 88t European Union, wheat production and consumption in countries of, 9, 289 Evolus, 162, 163t Exercise. See also Wheat-dependent exercise-induced anaphylaxis efficacy of soy peptides in, vs. with soy protein, 267 improvement in hypertension and, 43 overexertion during, reactive oxygen species and, 16 Exogeneous protein/peptide antioxidants, purpose of, 16 Exopeptidases debittering and, 354 reducing bitterness of protein hydrolysates and, 350 Expander cooker, rice bran stabilization and, 235 Extended class of proteins and peptides, 361 Extendin-4, 141 F Fahmi, A., 210t, 211, 213t Fahr, A., 371 Faipoux, R., 144 Familial amyloidosis, 90 Farina, 289 Farm animals, colostral Ig preparations for, 156

FAS. See Fatty acid synthase Fatal familial insomnia, 90 Fat dysfunction, 71 Fat replacers, rice bran as, 239–240 Fats, removing from bran, advantages with, 235–236 Fat substitutes, rice-based, 243 Fatty acids, unsaturated, oxidation of, 214 Fatty acid synthase, 71 FDA. See U.S. Food and Drug Administration FDEIA. See Food-dependent exercise-induced anaphylaxis FD-RBPs. See Freeze-dried rice bran proteins Fecal lactoferrin, use of, as diagnostic tool, 194 Feline calcivirus, Lfcin’s antiviral activity against, 192 Fermentation products, 171–173 Fermented dairy products, novel applications of bioactive peptides and, 161–162 Fermented food, bioactive peptides and, 326 Fermented milks, bLf added to, 193 Ferreira, S. H., 170 Ferritin, 37 Ferulic acid, 92, 126 FFAs. See Free fatty acids FGF1, in bovine mammary secretions, 152, 161 FGF2, in bovine mammary secretions, 152, 161 Fibrinogen alpha-chain, 88t Fibroblast growth factor, in bovine mammary secretions, 152, 161 Fibrosarcomas, Lfcin’s antitumor effects against, 192 Fickian diffusion model, drug release measured by, 372 Filamentous fungi, Lfcin and inhibiting growth of, 192 Findeis, M. A., 94 Fish collagen, sensitivity of, 204 Fish gelatin, 204–207 Bloom value and, 206–207 chemical composition of, 205

Index

demand for, 205 physical and chemical properties of, 205 properties and production processes for, 206 Fish muscle and collagen, bioactive peptides and protein from, 8 Fish peptides, antioxidant, 215–218 Fish processing, utilizing and upgrading waste from, 203 Fish products, bioactive peptides isolated from, 171 Fish proteins, 215 ACE inhibitory peptides derived from, 207–214, 209–210t ACE and blood pressure, 207 ACE inhibition mechanism, 211–212 ACE inhibitors, 207–208 ACE inhibitory peptides isolated from fish proteins, 208 in vitro ACE inhibition by peptides derived from fish proteins, 208, 211 in vivo ACE inhibition by peptides derived from fish proteins, 212–214 antioxidant peptides derived from, 214–215, 217t enzymatic oxidation, 214–215 mechanism of lipid oxidation, 214 overview, 214 food antioxidants and, 215–218 antioxidant fish peptides, 215–218 natural antioxidants, 215 synthetic antioxidants, 215 health benefits of, 204 hypotensive effects of fish-derived peptides in spontaneously hypertensive rats, 213t Fish sauce ACE inhibitory peptides isolated from, 208 inhibitory activities in, 172 Fish skin, as source of gelatin, 205 Fish supplies, threats to, 203

Flavonoids, 16, 215 Flavor, synergistic interactions with effect on, 344 Flavor-active components consumer acceptance and, 341 novel therapeutic approaches to chronic diseases and, 355 Flavor enhancers, rice bran proteins as, 238–239 Flavor ingredients amino acids interacting with, 352 peptides and protein hydrolysates interacting with, 352–353 proteins interacting with, 353–354 Flavourzyme, 238, 350 Flavourzyme hydrolysate, 275, 280 Flaxseed, omega-3 fatty acids in, 58 Flaxseed protein-derived cationic peptide fractions effect of, on intrinsic fluorescence of Ca2+/CaM-dependent nitric oxide synthases, 59–60, 60t kinetics of inhibition of neuronal nitric oxide synthase by, 59 Flaxseed protein-derived peptides as calmodulin inhibitors, 58–62 effect of on intrinsic fluorescence of calmodulin, 61, 61t on secondary structure fractions of calmodulin, 61, 61t Fluorescein chemical structure of, 374 penetration of, into human epidermis after treatment with magainin + NLS, 375 Fluorescein delivery, transdermal, enhancement of as function of pH, 374, 374 Fluorophores, two-photon microscopy and imaging of, 376 Folic acid, from animal muscle, 225 Foltz, M., 140 FONDAPARINUX, 318 Food allergens B- and T-cell epitopes, 105–106 “big eight,” 111, 114 molecular properties of, 105

395

Food allergy, 112–113 B-cell epitope mapping and, 107 current management of, 107–108 defined, 7, 101–102 egg allergy model, 113–114 IgE-mediated, potential immunotherapeutic approaches for, 109t novel immunotherapeutic strategies for, 108 peanut allergy model, 113 PIT investigations and murine models of, 116 sequence of events leading to type 1 hypersensitivity, 104 T-cell epitope mapping and, 106–107 T lymphocytes and role in, 103–105 wheat and beef allergy model, 114 Food antigens, allergic response to: two-phase mechanism, 103 Food antioxidants, 215–217 antioxidant fish peptides, 215–218 natural antioxidants, 215 synthetic antioxidants, 215 Food-based hydrolyzates, food allergy and, 109–110 Food choices, improvement in hypertension and, 43 Food-color carriers, rice bran proteins as, 239 Food-dependent exercise-induced anaphylaxis, 296 Food industry, lysozyme used in, 251 Food intake inhibition high-protein preload and, 136–137 satiety and, in high-protein diets, 137–138 Food intake in humans, physiological and psychological factors related to, 135 Food preservation and safety, lactoferrin and, 194 Food products, lipid oxidation in, 214

396

Index

Food protein-derived calmodulin-binding peptides, typical protocol during production of, 57, 57 Food protein-derived peptides as calmodulin inhibitors, 55–64 flaxseed protein-derived peptides, 58–62 milk protein-derived peptides, 56–58 pea protein-derived peptides, 62–64 Foods for specified health use, 6, 8 antihypertensive peptides in, 171t antihypertensive products, 44t design of ACE inhibitory peptides and, 45 in Japan, 43 in the market, 170–171 Food systems, antioxidant activity of peptides in, 34–35 FOSHU. See Foods for specified health use Fourier transform-ion cyclotron resonance, 310 Fourier transform-Raman spectroscopy, predicting bitterness of peptides and, 348 FOXp3 molecules, food allergy and, 116 Fractionation of bioactive milk proteins and peptides, 153, 162 immune milk preparations and, 156 Franco, O. L., 283 Free amino acids benefits related to protein hydrolysates consisting of, 344 reducing bitterness of protein hydrolysates and, 350 taste of foods and, 344 Free fatty acids, 70 Free radical attacks, disease, pathogenesis and, 29 Free radical oxidative reactions, termination of, 214 Free radicals, defined, 15

Freeze-dried rice bran proteins, 237 Fricker, L. D., 316 Friend virus complex, lactoferrin’s effects against, 185 Froetschel, M. A., 142 Fruits, natural antioxidants in, 215 FT-ICR. See Fourier transform-ion cyclotron resonance Fujita, H., 209t, 210t, 213t Full-fat-stabilized (FFS) bran, protein extraction from, 236 Full-fat-unstabilized (FFU) bran, protein extraction from, 236 Fumio, T., 123 Funa-sushi, GABA synthesis and, 126 Functional foods. See also Soy peptides as functional food system with antihypertensive effects, 169–175 global interest in promotion of, 162 in the market, 170–171 mode of action ACE inhibitory effects, 174 peptide absorption, 174 preparation of ACE inhibitory peptides, 171–173 enzymatic hydrolysis, 171 fermentation products, 171–173 in vivo effect, 173–174 clinical trials, 173–174 effects on an animal model, 173 worldwide interest in, 326 Functional proteins, within nutraceutical food sector, 5 Fungi filamentous, Lfcin and inhibiting growth of, 192 lactoferrin and, 187 Fusarium oxysporum, sativin’s antifungal activity against, 282 Fuzeon, 115 G GABA. See Gamma-aminobutyric acid

GABA-A receptors, mood regulation in animals and, 124 GABA-B receptors, mood regulation in animals and, 124 GABA shunt, 127 GABA-T, 127, 128, 129 GABA tea, 125, 129 GAD. See L-glutamic acid decarboxylase GAD65 molecule, 128 GAD67 molecule, 128 GAGs. See Glycoamino-glycans Gamma-aminobutyric acid, 121–130 animals and roles of, 124–125 curing neurological disease, 124 hypotensive effects, 125 inhibiting acute hyperaammonemia, 125 mood regulation, 124 preventing brain senescence, 124–125 sleep regulation, 125 weight loss, 125 biological functions of, 121 biosynthesis of, 127t biosynthetic pathway and metabolism, 130 conversion of intermediate to, 128 discovery of, 7, 121 formation of Schiff-base by substrate and PLP, 128 functions of, 122–125 human application of, 129–130 metabolic pathway of, 127–129 neutral and zwitterionic structures, 122 physical properties of, 122 preparation of, 125–127 other foodstuffs, 125–126 synthesis by microbes, 126–127 in tea, 125 properties of, from lactic acid bacteria, 123t proposed transformation of L-Glu to, by GAD, 129

Index

reaction mechanism of, 127 roles of synthesis, in plants, 122–124 nitrogen storage, 123 pH regulation, 123 plant defense, 123 plant development, 123–124 potential modulator of ion transport, 124 Garden/green pea (Pisum sativum), 9, 273, 274 anticancer effects due to Bowman-Birk inhibitors and, 278 antimicrobial peptides from, 281–282 antioxidant effects of, 274–275 future prospects for biological activities related to, 284 hypocholesterolemic effects and, 276 Gardenia jasminoides Ellis, 18 Gastric inhibitory peptide, 76 Gauthier, S. F., 161 GBR. See Germinated brown rice Gejyo, F., 88t Gelatin antioxidant activity of peptides in, 34 antioxidant proteins/peptides in, 17 bitterness masked with, 350 fish, 204–207 Gel filtration, whey protein isolates and, 154 Gelsolin, 88t “Generally Recognized as Safe” designation, 159 Genistein, 92 Gerber, S. A., 315 Germ, 233 rice kernel, 234 German-Straussler-Scheinker syndrome, 90 Germinated brown rice, GABA used in, 126, 129 GH. See Growth hormone Ghrelin food intake and, 141–142 protein and, 74

GHRH. See Gonadotrophichormone-releasing hormone Giant squid, antioxidant peptides from, 217t Giardia lamblia, Lfcin’s effects on, 192 GI enzymes, antioxidant peptides and, 32 Giméneze, B., 217t GIP. See Gastric inhibitory peptide Giroux, I., 276 GJE. See Gardenia jasminoides Ellis Glenner, G. G., 88t Gliadin, 10, 290, 291–293, 295 Globulin, 247 Glucagon-like peptide-1 (GLP-1), 139 anorexigenic actions of, 141 effect of 3-hour intravenous infusions of, on cumulative food intake in rats, 141 protein and, 74 protein-induced satiety and, 138 short-term, 145 Glucagon secretion, dietary proteins and, 76 Glucofructans, 233 Gluconeogenesis, protein-induced satiety and, 145 Glucose, as metabolic signal in protein-induced satiety, 142 Glucose 6-phosphatase (G6Pase), protein-induced satiety and, 142 GLUT-2, protein and, 75 Glutamate, taste of, 344 Glutamate decarboxylase, 122 Glutamic acid, 37, 238 Glutamines, in rice bran proteins, 238 Glutathione aerobic organisms and, 16 in animal muscle, 225 antioxidant activity and, 30, 31t chemical structure of, 31 redox homeostasis and, 16 Glutathione peroxidase, aerobic organisms and, 16 Glutathione reductase, aerobic organisms and, 16

397

Glutathione synthetase, 16 Glutelin, 290, 293, 295 Gluten, 295 viscoelastic property of, 9–10, 295, 299 Glutenin, 290, 293, 295 Glutenin subunits, repeat motifs in structure of, 293, 295 Gly, in gelatin, 205 Glycemic control, soy protein and, 74–76 Glycerol monooleate, 361 Glycine bitterness masked with, 350 sweet taste of, 343 Glycinin, 17 Glycoamino-glycans, lactoferrin binding to, 186 Glycomacropeptide, 19, 20t anti-inflammatory properties of, 20t, 21 health benefits with, 160 purification of, from bovine colostral or cheese whey, 154 whey proteins and, 160 Glycosylated peptides, enrichment of, 314 Gly-Thr-Trp, 155 Gly-Val-Trp, 155 GM-CSF. See Granulocytemacrophage colony stimulating factor GMO. See Glycerol monooleate GMO cubic phase, PT cubic phase vs., in hydrophilic fluorescent model drugs investigation, 379 GMO/water cubic phase, insulin protected from agitation-induced aggregation and, 365 GMO/water systems diffraction patterns of, with incorporated insulin, 364 small-angle x-ray scattering patterns and lattice constants a of lamellar and cubic phases of, loaded with 4% insulin, 364

398

Index

GMP. See Glycomacropeptide Gonadotrophic-hormone-releasing hormone, angiotensin II and, 207 G protein-coupled receptors (GPCRs), 342 GPR93 receptor, 140 GPx. See Glutathione peroxidase GR. See Glutathione reductase Gramicidin, liquid crystalline phases and, 363 Gramicidin A, space-filing model of channel form of, 362 Gramicidin D, 361 Gram positive/gram negative bacteria LfambinB peptide’s activity against, 193 LfcinB and LfcinH actions against, 191, 192 lysozyme and, 250, 251 Gram positive/negative pathogens, lactoferrin and, 185, 186 Granisetron, chemical structure of, 374 Granulocyte-macrophage colony stimulating factor, lactoferrin and production of, 189 Grape seed extracts, 30 GRAS. See “Generally Recognized as Safe” designation Grass carp, antioxidant peptides from, 217t Green tea extracts, 30 GABA content in, 125 Grosman, M. V., 236 Growth factors, 7–8, 151, 307 in bovine colostrum and milk, 153t in mammary secretions, 152–153, 160–161 Growth hormone, changes in, after beverage ingestion: comparison of placebo, soy protein, and soy peptide on GH and CPK level, 268 GS. See Glutathione synthetase GSH. See Glutathione

GSSG, 16 Guérin-Dubiard, C., 249t H Habener, J. F., 140 Haemophilus influenzae, lactoferrin’s antimicrobial activities and, 158, 185, 186 Haggqvist, B., 88t Hall, W. L., 138, 141 Halorhodopsin, 361 Hardeland, R., 31t Hartog, A., 20t Hata, I., 20t Haversen, L., 22 Hayashida, K., 20t Health promotion, bioactive peptides and proteins and, 5 Heart disease, chronic inflammation and, 227 Heat stabilized rice bran, 242 HEL. See Hen egg lysozyme Helicobacter pylori immune milk preparations and, 156 lactoferrin’s antimicrobial activity and, 158 lactoperoxidase system and, 160 Helix-loop-helix pattern, lysozyme and, 251 Hemicelluloses, 233 Hemodialysis-associated disease, 89, 90 amyloid deposits and, 95 amyloidosis and, 7 Hen egg lysozyme, anti-inflammatory activity with, 19 Hen eggs as important food worldwide, 258 lysozyme in, 250 Hen egg yolk phosvitin, 17, 18 Heparan sulphate, 186 Hepatic lipogenesis, soy protein feeding in rats and, 71 Hepatitis B, lactoferrin’s effects against, 185 Hepatitis C bLf, IFN therapy and eradication of, 189

lactoferrin’s effects against, 185, 186 Hepatitis viruses, lactoferrin’s antimicrobial activity and, 158, 159 Herbal medicine anti-inflammatory mechanisms and, 23 antioxidative stress proteins and peptides in, 18 Herbs, natural antioxidants in, 215 Hernandez-Ledesma, B., 37t Herpes simplex virus lactoferrin’s antimicrobial activity and, 158 lactoferrin’s effects against, 185 Herring, antioxidant peptides from, 217t Herring fish protein hydrolysate, antioxidative activity of, 218 Herring processing wastes, enhancing gelatin from, 205 Hexagonal phase time course of in vitro skin penetration and percutaneous delivery of cyclosporin A incorporated in, 369–370, 370 in vivo skin penetration of CysA incorporated into, compared to olive oil formulation, 371, 371 Hexane, 214 “Hidden allergens,” 107 High blood pressure, cardiovascular disease and, 207 High-density lipoprotein cholesterol, metabolic syndrome and, 67, 68t High-density lipoproteins in egg yolk, 248 soy protein and, 76 High fructose corn syrup, 351 High-molecular-weight glutenin, 293 High-protein diet, defined, 137 High-protein meal, high-protein diet vs., 137

Index

High-protein preload, high-protein meal-induced satiety and food intake inhibition and, 136–137 Himeno, K., 126 HINUTE-AM launching of, 266 typical analysis of, 267t Hipkiss, A. R., 227 His amino acid, potent antioxidant activity with, 17 Histadyl dipeptides carnosine and anserine, 225, 226 health benefits with, 226 Histidine, 29 antioxidant activity of peptide derived from hoki skin, 218 antioxidant behavior in peptides, 216 food intake and, 142–143 radical quenching activity of peptides and, 35 HIV-1, lactoferrin’s antimicrobial activity and, 158 HLA. See Human leukocyte antigen HLA-DQ2, celiac disease and, 297 HLA-DQ8, celiac disease and, 297 HLA-DR, expression of seven alleles of, in Caucasian population, 115 hLf effect of, on angiogenesis, 189–190 sequences of Lfcin and Lfampin peptides from, 184t Hockerman, G. H., 50 Hoie, L. H., 77t Hoki, antioxidant peptides from, 217t Hoki skin branched amino acids present in antioxidant peptides from, 216 histidine and antioxidant behavior of peptide derived from, 218 Holst, J. J., 141 Holton, J. L., 88t Hormone replacement therapy, transdermal route of administration and, 360

Host cells, adsorption of lactoferrin in, 187 Howell, N. K., 206 HS. See Heparan sulphate HSRB. See Heat stabilized rice bran HSV, Lfcin’s antiviral activity against, 192 Human immunodeficiency virus lactoferrin binding to co-receptors of, 186–187 lactoferrin’s effects against, 185, 186 Lfcin’s antiviral activity against, 192 Human leukocyte antigen, 115 Human Lfcin (LfcinH), structure of, 185 Humiski, L. M., 275, 280 Humulin, aggregation profiles of, 365, 365 Huntington protein, 92 Huntington’s disease, 90, 92 amyloid deposits and, 89 treharose and, 95 HVP. See Hydrolyzed vegetable protein Hydrolysis of proteins, desirable sensory attributes with, 344–345 Hydrolyzed vegetable protein, 352 Hydrophilic fluorescent model drugs, distribution of, in full-thickness human skin, 376–377, 378t, 379 Hydrophilic pathways, of drug penetration, 368, 369 Hydrophobicity, bitterness and, 345, 347 Hydroxyl radicals, 29 Hydroxyproline in collagen, 204 in fish gelatins, 206 Hyperammonemia, acute, GABA and prevention of, 125 Hyper-hypo-response phenomenon, cholesterol-rich diets and, 277 Hyperinsulinemia metabolic syndrome and, 67 soy protein consumption and, 75, 76

399

Hypertension, 71. See also Antihypertensive peptides cardiovascular disease and, 169, 207 improving treatment of, 6 metabolic syndrome and, 67, 68t morbidity and mortality related to, 256 overconsumption of salty and sweet foods and, 342 renin-angiotensin system and, 44 sodium substitutes and, 345 soy protein and, 79–80 wheat peptide and prevention of, 298–299 Hypoallergenicity, tolerogenicity vs., 112–113 Hypotension, gamma-aminobutyric acid and, 125 Hypothalamus food intake, energy homeostasis and, 144, 144 food intake regulation and, 145 I IAPP. See Islet amyloid polypeptide Ibrahim, H. R., 249t ICAT. See Isotope-Coded Affinity Tag IC50 value, potency of ACE inhibitory peptide and, 208 IgE. See Immunoglobulin E IgE-mediated food allergy etiology of: two-phase phenomenon, 103 potential immunotherapeutic approaches for, 109t IGF-I in bovine colostrum vs. in human colostrum, 153 in bovine mammary secretions, 152, 161 IGF-II in bovine colostrum and milk, 153 in bovine mammary secretions, 152, 161 Ikemoto, F. IL-6. See Interleukin-6 IL-8. See Interleukin-8

400

Index

IL-10. See Interleukin-10 IL-beta. See Interleukin-beta Ile-Ala-Pro, hypertension prevention and, 299 Ile-Pro-Pro, 162, 172 absorption of, 174 antihypertensive effect of milk tested in hypertensive patients and, 173 casein hydrolyzate with, 170 hypotensive capacity of, 155 Ile-Tyr, vascular relaxation effect of, in 18-week-old SHR thoracic aorta rings constricted by 30 mmol/L KCI, 49 Ile-Val-Tyr, hypertension prevention and, 299 Immobilized metal affinity capture (IMAC), 314 Immune-enhancing nutraceuticals, bLf added to, 193 Immune milk, history behind concept of, 156 Immunoglobulin E, common form of food allergy mediated by, 102 Immunoglobulin heavy chain, 88t Immunoglobulin light chain, 88t Immunoglobulins (Igs), 7, 105–106, 151 in bovine colostrum and milk, 153t in colostrum, 152 whey proteins and, 156 Immunomodulating proteins and peptides, 254–255, 326 Immunostimulating peptides, 169 Incretins, 76 India, wheat production and consumption in, 9, 289 Indonesian dried-salted skipjack tuna, ACE inhibitory activity exhibited by, 211 Inducible isozyme, of NOS (iNOS), 56 Inducible Tregs, food allergy and, 104 Infant formulas, bLf and, 193

Infections, lactoferrin’s efficiency against, 193 Inflammation cell signaling mechanisms associated with, 19 chronic disease and, 6, 23 reactive oxygen metabolites and, 226 reactive oxygen molecules and, 18 reactive oxygen species and, 16 at root of chronic diseases, 227 Inflammatory bowel disease fecal lactoferrin and, 194 free radical attacks and, 29 lactoferrin’s anti-inflammatory role in, 187 Inflammatory diseases lactoferrin as clinical marker of, 194 lactoferrin’s efficiency against, 193 Inhalant allergens, PIT investigations carried out with, 114 in meso crystallization process, description of, 361 Inoue, K., 125 In silico analysis, of proteins and bioactive peptides, 326–328, 331 Insulin, 88t changes in circular dichroic spectra of, in solution and cubic liquid crystal compared with control insulin, 366, 367 GMO/water system loaded with, 363–365, 364 monomer as biologically active form of, 363 protection of, from agitationinduced aggregation and GMO/water cubic phase, 365, 366 Insulin A chain, 93t Insulin B chain, 93t Insulin/glucagon (I/G) ratio, soy protein consumption and, 76

Insulin-like growth factor, in bovine mammary secretions, 152, 161 Insulin molecule, dimeric, schematic representation of, 363 Insulin resistance metabolic syndrome and, 67, 69 soy protein and, 74–76, 75 Intercellular route of administration, across stratum corneum, 368, 368 Interleukin-6, 18 Interleukin-8, 18, 19 Interleukin-10 food allergy and, 104, 116 lactoferrin and, 187, 188 Interleukin-beta, 18–19 Intestinal inflammation, fecal lactoferrin and, 194 Intestine mucosal barrier, allergic response and, 102–103 Intramuscular route of administration, for biopharmaceuticals, 360 Intravenous injections, of biopharmaceuticals, difficulties related to, 360 In vitro protein digests, antioxidant activity of, 32–34 Ion transport, gamma-aminobutyric acid and modulation of, 124 IR. See Insulin resistance Iron, from animal muscle, 225 Iron-binding properties, of lactoferrin, 181–182 Ishikado, A., 20t Islam, fish gelatin acceptable for, 205 Islet amyloid polypeptide, 88t, 91, 93t Isoflavones, 30 Isoleucine ACE inhibitory activity, bitterness and, 348, 349 bitterness associated with, 343 Isotope-Coded Affinity Tag, 316 Isotope Tags for Relative and Absolute Quantification, 316 Itou, K., 213t

Index

J Jao, C. L., 217t Japan fish consumption in, 171 foods for specified health use in, 43 number of hypertensives and high-normal hypertensives in, 43 wheat production and consumption in, 289 Japanese fermented foods, ACEI peptides analysis in, 172–173 Japanese Minstry of Health, Labour and Welfare, 43 Je, J. Y., 210t, 217t Jean, C., 144 Johansson, B., 88t Johnson, J., 141 Johnson, P., 31t Johnstone, A. M., 137 Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure criteria, 80 Judaism, fish gelatin acceptable for, 205 Juices, antioxidant caseinophosphopeptides in, 35 Julka, S., 315 Jumbo flying squid, antioxidant peptides derived from, 217t, 218 Jun, S. Y., 37t, 217t Jung, W. K., 210t, 213t, 217t

Kawashima, K., 216 Kazuhito, A., 123 KDR/Flk-1, lactoferrin and, 190 Kerato-epithelin, 88t Kernel, 233 Kieffer, T. J., 140 Kim, H-O, 345, 348 Kim, K. S., 31t Kim, S. K., 210t, 217t Kim, Y-C, 373, 374 Kingman, S. M., 277 Kinin-nitric oxide system, blood pressure regulation and, 207 Kininogen, 207 Kinnersley, A. M., 124 Kizawa, K., 58 Klompong, V., 217t KNOS. See Kinin-nitric oxide system Ko, W. C., 217t Kobayashi, H., 20t Kodera, T., 350 Kohama, Y., 209t Kohno, M., 77t Komatsu, T., 269 Komatuszaki, N., 126 Konig, D., 78t Kono, I., 126 Korpela, J., 249t Korvatska, E., 88t Kosmotropes, 362 Kosmotropic solutes, properties of liquid crystalline phases and, 362 Kovacs-Nolan, J., 249t Kraineva, J., 363 Kruzel, M. L., 159 Kunitz trypsin inhibitor (KTI), soyderived, anti-inflammatory mechanisms and, 20t, 22–23 Kuru disease, 90

K Kallikrein, 207 Karagiannis, E. D., 318 Karelin, A. A., 325 Kasaoka, S., 143 Katayama, S., 256 Katsuobushi (dried bonito) oligopeptide, 43, 44t

L LAB. See Lactic acid bacteria Lactadherin, 88t Lactalbumin alpha Lactalbumin alpha, bovine chromatograms of, 336, 338 mass spectrum of tryptic hydrolysate of, 338

iTRAQ. See Isotope Tags for Relative and Absolute Quantification

401

profile of potential biological activity of, 337 Lacteal secretions, in vivo activities of lactoferrin in, 157 Lactic acid bacteria, 240 antioxidant activity of, 38–39 fermented products and, 172 GAD properties from, 123t Lactic acid bacteria (LAB)-based starter cultures, proteolytic properties of, 155 Lactobacillus, GABA biosynthesis with, 126 Lactobacillus acidophilus, high radical-scavenging activity in, 39 Lactobacillus brevis, GABA content and, 126–127 Lactobacillus casei, 21 Lactobacillus helveticus ACE inhibitory peptides isolated from, 172 antihypertensive peptides and, 155 effect of, in spontaneously hypertensive rat, 173 Lactobacillus helveticus-fermented milk (sour milk), 44, 44t Lactobacillus jensenii, high radical-scavenging activity in, 39 Lactobacillus paracasei NFRI, GABA synthesis and, 126 Lactobacillus plantarum, lysozyme and, 251 Lactobacillus rhamnosus GG-degraded bovine casein, 21 Lactococcus lactis subsp. cremoris FT4, ACEI peptides produced in fermented milk started by, 172 Lactoferrampin, 180 Lactoferricin, 180 Lactoferrin (Lf), 7, 20t, 88t, 151, 250 anti-inflammatory activity associated with, 20t, 21–22 antitumor activity of, 158 applications of, and related peptides, 193–194

402

Index

Lactoferrin (continued) beneficial health effects with, 158 biological roles of, in cancer and cell proliferation, 189–191 biological roles of, in host defense, 185–189 anti-inflammatory properties of, 187–188 antimicrobial activities of, 185–187 pro-inflammatory properties of, 188–189 in bovine colostrum and milk, 153t characteristics of, 180 iron-binding properties and dynamics of, 181–182 localization of Lfcin domain and Lfampin sequence on, 183 mechanisms related to antimicrobial activity of, 157–158 overall structure of, 181 protective effects of, 8, 179 secreted, origin of, 180 structure of, 180–181 gene structure and amino acid sequence, 180 glycosylation of, 181 in 3D, 181 structure of biologically active peptides of, 182–185 biologically active peptide sequences of, 182–184 structure of Lfampin, 185 structure of Lfcin, 184–185 whey proteins and, 157–159 Lactoferrin-related peptides biogical properties and mechanisms of, 191–193 of Lfampin, 193 of Lfcin, 191–193 Lactoglobulin beta, 334 Lactoperoxidase, 151 in bovine colostrum and milk, 153t in colostrum, 152 health benefits with, 159 whey proteins and, 159–160 Lactotransferrin, 180

Lagarde, G., 249t Lam, 281, S. S. L. Lamellar phase, delivery of proteins and peptides in, 360, 363 L-amino acids bitterness associated with, 343 taste, detection threshold, and taste-enhancing effects of, 343t Lang, V., 138. Lasekan, J. B., 277 Late embroygenesis-abundant protein group, 237 Lateral hypothalamus with orexin-containing neurons, detection of high-protein meals and, 145 satiety and, 143 Latham, C. J., 143 Laying hens, feeding formula for, 239 L-carnitine in animal muscle, 225 antihypertensive and cardiovascular effects of, 227 health benefits with, 226 hypotensive effect of, 227–228 LEA protein group. See Late embroygenesis-abundant protein group Lectins, rice bran, 241–242 Lee, M., 19, 20t Lee, S. J., 20t Lee, Y. J., 320 Legionella pneumophila, lactoferrin’s antimicrobial activities and, 185 Legnin, 233 Legumes health promotion and, 9 natural antioxidants in, 215 as sources of dietary protein, 273 Legumin, in chickpea seeds, 280 Lejeune, M. P., 141, 142 Leptin, 70, 71 Leucine, 248 ACE inhibitory activity, bitterness and, 349 bitterness associated with, 343 food intake and, 143

Leuconostoc mesenteroides ssp., high radical-scavenging activity in, 39 Leu-Lys-Pro, antihypertensive effects of, in spontaneously hypertensive rat, 173 Leu-Lys-Pro-Asn-Met antihypertensive effects of, in spontaneously hypertensive rat, 173 preparation of, 171 Leu-Val-Tyr, preparation of, 171 Leventhal, A. G., 125 Lf. See Lactoferrin Lfampin biological properties and mechanisms of, 193 sequences of, from hLf and bLf, 184t structure of, 185 LfampinB peptide, 193 LfampinH, 193 Lfampin sequence, localization of, on lactoferrin, 183, 183 Lfcin, 191 antimicrobial activities of, 194 biological properties and mechanisms of, 191–193 sequences of, from hLf and bLf, 184t structure of, 184–185 LfcinB, actions of, against bacteria, 191 Lfcin domain, localization of, on lactoferrin, 183, 183 LfcinH, actions of, against bacteria, 191 Lf gene, transcription of, 180 L-glutamic acid decarboxylase biosynthetic pathway and GABA metabolism and, 130 proposed transformation of L-Glu to GABA by, 129 L’Heureux-Bouron, D., 142 Li, B. F., 217t Li, H., 62 Liao, F-H, 77t Li-Chan, E. C. Y., 345, 348 Lichtenstein, G. R., 20t

Index

Lifestyle modifications, hypertension management and, 43 Lim, K. T., 20t Lin, F., 124 Lin, L., 217t Linke, R. P., 88t Linoleic acid, 216 Lipases, isolated from rice bran, 238 Lipid metabolism, efficacy of soy peptides on, vs. with soy protein, 267 Lipid oxidation inhibiting, 216 mechanism of, 214 Lipids, 105 free radical attacks on, 29 functions of, 214 Lipid transfer proteins, 283 Lipophilic pathways, of drug penetration, 368, 369 Lipopolysaccharides inflammation and, 18 lactoferrin and, 187, 188 Lipoprotein Receptor-related Protein, 182 Liposomes with ethanol, penetration experiments of CysA and, 371 Lipoxygenase, 214, 215 Liquid chromatography, investigating bioactive peptide proteins with BIOPEP database and, 336 Liquid crystalline phases cubic and hexagonal time course of in vitro skin penetration and percutaneous delivery of CysA in, compared to olive oil control formulation, 369–370, 370, 371 in vivo skin penetration of CysA in, compared to olive oil as control formulation, 371, 371 delivery of proteins and peptides and, 360, 379 Liquid crystalline systems, entrapment and stability of proteins and peptides by, 360–366

Liquid crystal mesophases (“in meso” method), 361 Lisinopril, 208 Listeria monocytogenes, lactoferrin’s antimicrobial activities and, 158, 185 Liu, W., 361 Livetin, in egg yolk, 248 Localized amyloidosis, 90 Loop class of proteins and peptides, 361 Lopes, L. B., 369, 371 Lovati, M. R., 79 Low-density lipoproteins, in egg yolk, 248 Low-molecular-weight glutenin, 293 LOX. See Lipoxygenase LOX-1, 215 LOX-2, 215 LP. See Lactoperoxidase LPS. See Lipopolysaccharides LPS-binding protein (LBP), 187 LRP. See Lipoprotein Receptor-related Protein L68Q cystatin C, 90, 91, 91, 92 LTPs. See Lipid transfer proteins Lukaszuk, J. M., 78t Lung tumors, in mice, Bowman-Birk inhibitors and, 278 Luppi, P. H., 125 Lutein, 30 LXR alpha, soy protein and, 79 Lycopene, 30 Lys amino acid, potent antioxidant activity with, 17 Lysine ACE inhibitory activity, bitterness and, 349 in cereal grain proteins, 234 sweet and bitter taste of, 343 Lysozyme (LZM), 19, 20t, 88t, 247, 258 antimicrobial activity of, 250 antimicrobial peptides from, 251–252 antioxidant activity of, 256 in bovine colostrum and milk, 153t in cow’s colostrum, 152 in egg white and shell membranes, 249–251

403

hen, 93t human, 93t immunomodulating properties of, 254–255 sweetness threshold value of, 351 LzP, antimicrobial activity of, 251–252 M Mackerel antioxidant peptides from, 217t hypotensive effects of, in spontaneously hypertensive rats, 213t Macromolecules, increasing permeability of, new technologies for, 360 Maebuchi, M., 266 Magainin, penetration of fluorescein into epidermis after treatment with N-lauroyl sarcosinen and, 375, 375 Magainin peptides, skin permeability and, 373–376 Maize zein, antioxidant activity of, 216 Makin, O. S., 89 MALDI, 310 MALDI-Q-TOF, 310 MALDI-TOF-MS, 310 Mammalian Target of Rapamycin model for role of, in hypothalamic regulation of energy balance, 144 satiety, high-protein diets and, 143 Mammals, metabolic pathway in, 127 Manganese, 215 MAPKs. See Mitogen activated protein kinase Marine peptide, 171t Mass spectrometry investigating bioactive peptide proteins with BIOPEP database and, 336 peptidomics and, 307, 308, 309–311 Mastitis, lactoferrin and prevention of, 194 Masuda, K., 267

404

Index

Matsufuji, H., 209t, 213t Matsui, T., 174, 209t Matsumura, N., 209t Matthews, D. M., 265 Maury, C. P., 88t Mayonnaise, antioxidant caseinophosphopeptides in, 35 MBP. See Milk basic protein M cells, 102 MCP-1. See Monocyte chemoattractant protein 1 MDA-MB-231 breast cancer line, lactoferrin and, 190 Meat products lysozyme and bacteria control in, 251 rice bran proteins in, 239 Medium-chain acyl-CoA dehydrogenase, soy protein feeding in rats and, 73 Melanomas, Lfcin’s antitumor effects against, 192 Melatonin antioxidant activity and, 31, 31t chemical structure of, 31 Melittin, liquid crystalline phases and, 363 Membrane proteins, as important diagnostic and prognostic markers, 313 Membrane separation technique, for fractionation and isolation of bioactive milk proteins, 153 Mendis, E., 217t Mero, A., 161 Metabolic disorder, flavor-active components and novel therapeutic approaches to, 355 Metabolic parameters, soy protein diets and effect on, 77–78t Metabolic syndrome. See also Diabetes; Obesity; Soy protein for metabolic syndrome chronic inflammation and, 227 criteria for definitions and diagnosis of risk factors in, 68t

incidence of, 67 milk-derived components and reducing risk of, 155 pathogenesis of, 69–71, 70 quintet of factors in, 67 soy protein action on insulin resistance in, 75 soy protein and, 6 sweet proteins and, 351 whey proteins and, 152 Metal-ion binders, 37 Metal-ion catalysts, sequestering, peptides inhibiting oxidative processes and, 37 Metallo-collagenase MMP-13, 205 Metal prooxidants, sequestering and stabilization of, 37 Met amino acid, potent antioxidant activity with, 17 Metastasis, lactoferrin as defense against, 189 Methionine, 29 in cereal grain proteins, 234 hypocholesterolemic effects of pea proteins and levels of, 276–277, 277 radical quenching activity of peptides and, 35 MHC polymorphism, food allergy and, 115 Microalbuminuria, metabolic syndrome and, 68t Microbe fermentation, 172 Microbes, lactoferrin binding to, 186 Microbial fermentation, antioxidant peptide preparation with, 38–39 Microbial growth, rice bran as substrate for, 240 Microencapsulation, bitter taste reduction and, 354 Microorganisms, GABA synthesis by, 126–127, 127t Migraine headaches, nitric oxide levels and, 56 Mikkelsen, T. L., 20t, 21 Milk immune, history behind, 156 major bioactive whey proteins in, 153, 153t

Milk basic protein, bone-strengthening effects of, 161 Milk growth factors biological functions of, 161 health benefits with, 161 Milk lysozyme, anti-inflammatory activity with, 19 Milk peptides nutritional benefits with, 154 protein-derived, as calmodulin inhibitors, 56–58 Milk proteins, 215 antioxidative stress proteins and peptides in, 18 bioactive peptides and, 8 high nutritional value of, 7–8, 151 release of bioactive proteins from, 332 selected biopeptides released by trypsin from, 334, 336 Milk whey proteins, health benefits with, 155 Miller, D. J., 227 Miller, G. M., 30 Millet, rice protein net protein utilization compared to, 240 Mine, Y., 251 Minerals, 215 salty taste and, 342 soluble peptides, 169 Miraculin, 351 Mitogen activated protein kinase, 19 Miyagawa, S., 249t, 253 Molla, A., 249t Monascus, GABA biosynthesis with, 126 Monascus-fermented rice, 126, 129 Monascus purpureus CCRC 31615, GABA synthesis and, 126 Monellin, 351 Monnai, M., 20t Monoacylglycerols aqueous channel size, drug release rate and, 373 hydrated, effect of drug radius of gyration on transport from cubic phase of, 372 Monocolonal antibody-based products, 359

Index

Monocyte chemoattractant protein 1, 71 Monocytes, 19 Monoolein aqueous channel size, drug release rate and, 373 as penetration enhancer, 370 Monoolein cubic phase, summary of fluorescent features observed in two-photon microscopy images at various tissue depths of skin exposed to sulphorhodamine B in, 378t Monopalmitolein, aqueous channel size, drug release rate and, 373 Monosodium glutamate bitterness masked with, 350 protein hydrolysates used with, 238 Monovaccenin, aqueous channel size, drug release rate and, 373 Mood regulation, in animals, GABA and, 124 Moran, L. J., 142 Morrison, C. D., 143 MRM. See Multireaction monitoring MS. See Mass spectrometry; Metabolic syndrome MSG. See Monosodium glutamate mTOR. See Mammalian Target of Rapamycin Multidimensional protein identification technology (MudPIT), 313 Multifunctional peptides, in BIOPEP, characteristic activity of, 332 Multireaction monitoring, 310 Murai, T., 125 Murphy, C. L., 88t, 94 Muscle-based bioactive peptides, 8 Muscle protein, antioxidant acitivty of peptides in, 34 Mycoleptodonoide aitchisonii, aqueous extract from, 43–44, 44t Myofibrillar proteins, in fish proteins, 204

Myoglobin, 89, 93t Myosin, in myofibrillar tissue proteins, 204 Mytilus coruscus muscle protein, peptide with potent antioxidative activity from, 218 N N-acetyl-5-methoxytryptamine, 31 N-acetylglucosamine, 250 N-acetylmuramic acid, 250 N-acetylneuraminic residues, anti-inflammatory activity and, 21 NAG. See N-acetylglucosamine Nagai, T., 217t Nagasawa, T., 31t Nakajima, K., 210t, 352 NAM. See N-acetylmuramic acid Nanofiltration techniques, fractionation of bioactive peptides and, 155 National Cancer Institute Best Practices of Biospecimen Resources, 311 National Cholesterol Education Program, 67 Natto antioxidant peptides in, 38 inhibitory activities of, 172 Natural antioxidants, 215 Natural killer cells, food allergy and, 103, 105 Navab, M., 37t NCEP. See National Cholesterol Education Program NDGA. See Nordihydroguaiaretic acid Near infrared light, 376 Neoculin, 351 Neotame, 351, 355 NEPS. See Neutral endopeptidase system Net protein utilization, 240 Neuraminidase, 21 Neurodegenerative diseases lactoferrin and, 188 lactoferrin’s anti-inflammatory role in, 187

405

reactive oxygen metabolites and, 226 Neurological diseases, curing in animals, GABA and, 124 Neurological effects, muscle-based dipeptides and, 228 Neuronal isozyme, of NOS (nNOS), 56 Neuronal nitric oxide synthase, flaxseed protein-derived cationic peptide fractions and kinitecs of inhibition of, 59 Neuropeptides, 307, 319 Neuropeptide Y, satiety, high-protein diets and, 143, 144 Neutral endopeptidase system, blood pressure regulation and, 207 Neutrophils, 19 Ney, K. H., 345 Ng, T. B., 282, 283 Nguyen, S. D., 37t Nicholls, W. C., 88t Nicin, 250 Nicotinamide adenine dinucleotide phosphate oxidase complex, 16 Nielson, K. L., 249t Nilsson, M. R., 88t NIR. See Near infrared light Nitric oxide, excessive levels of, 56 Nitric oxide synthases, main isozymes of, 56 Nitrogen solubility index, 236 Nitrogen storage, of gamma-aminobutyric acid, 123 NK cell cytotoxicity, lactoferrin and promotion of, 189 N-lauroyl sarcosine (NLS) penetration of fluorescein into epidermis after treatment with magainin and, 375, 375 skin permeability study and, 374 NMBzA-induced esophageal tumors, Bowman-Birk inhibitors and, 278 Nomura, A., 210t Nonheat stabilized rice bran, 242

406

Index

Noninfectious pathologies, lactoferrin and, 188 Nonsteroidal anti-inflammatory drugs, colostrum-based products with growth factors and side effects of, 161 Noodles, instant, GABA used in, 129 Nordentoft, I., 76 Nordihydroguaiaretic acid, 92 Noriega-Lopez, L., 75 NOS. See Nitric oxide synthases Novel peptides, peptidomics and, 320 NPU. See Net protein utilization NPY. See Neuropeptide Y NSI. See Nitrogen solubility index NSRB. See Nonheat stabilized rice bran N-terminal helix, lysozyme and, 251 Nuclear factor-kappa B, inflammation and activation of, 18–19 Nuclear layer, bran, 233 Nucleic acid-based medicinal products, 359 Nucleic acids, free radical attacks on, 29 Nutraceuticals, growing demand for, 354. See also Functional foods Nuts, natural antioxidants in, 215 O OBBR. See Office of Biorepositories and Biospecimen Research Obese rat, blood lipid level of, 269 Obesity. See also Metabolic syndrome; Protein-induced satiety and food intake inhibitions; Satiation/satiety; Weight loss bioactive milk peptides and, 163 centripetal, metabolic syndrome and, 67 flavor-active components and novel therapeutic approaches to, 355 insulin resistance promoted by, 70 metabolic syndrome and, 68t, 71

overconsumption of salty and sweet foods and, 342 soy protein and, 6 sweet proteins and, 351 type II diabetes and, 67–68, 298 OCX-36. See Ovocalyxin-36 Odashima, M., 20t Odontogenic ameloblast-associated protein, 88t O’Dowd, A., 227 “Off-flavor” problems, interactions with proteins and, 353 Office of Biorepositories and Biospecimen Research, 311 Ogundele, M. O., 20t Oh, P. S., 20t Ohtsubo, K., 126 Oilseed proteins, antioxidant activity of, 216 Oilseeds, natural antioxidants in, 215 Ointment, commercial summary of fluorescent features observed in two-photon microscopy images at various tissue depths of skin exposed to sulphorhodamine B and, 378t two-photon fluorescence images showing lateral distribution of sulphorhodamine B, after 24 hours of passive diffusion in skin and, 377, 377, 379 Okamoto, A., 210t Okara, 266 Oligopeptidases, reducing bitterness of protein hydrolysates and, 350 Oligophosphopeptides, 17 Olive oil biophenols, 16 Omega-3 fatty acids, in flaxseed, 58 Ono, S., 210t Oolong tea, GABA content in, 125 Opioid peptides, 169 Oral administration of biopharmaceuticals, difficulties related to, 360 Oral health care products, lysozyme used in, 251 Oram, J. D., 159

Ornithyl-beta-alanine hydrochloride, salty taste attributed to, 345 Ornithyltaurine hydrochloride, salty taste attributed to, 345 Orthonasal contributions, to aroma perception, 354 Osajima, K., 208, 209t Osborne classification, cereal proteins and, 235 Osteoblast proliferation, lactoferrin and, 191 Osteoporosis, lactoferrin and, 191 Otani, H., 20t OTAP-92, 252 Ovalbumin, 247 antihypertensive peptides in, 257 antimicrobial peptides in, 252–253 in egg white, 254 in serpin family, 258 Ovocalyxin-36, 250 Ovoinhibitor, as serine protease inhibitor, 258 Ovokinin, 257 Ovomucin, 247 anticancer property of, 255 antimicrobial activity of, 253 immunomodulating properties of, 254 Ovomucoid, 247 Ovotransferrin, 247, 250 anti-inflammatory activity with, 19, 20t antimicrobial activity of, 252 antioxidant activity of, 256 immunomodulating properties of, 254 Ovo-vegetarians, egg proteins and, 249 Ovovmacroglobulin, antimicrobial activity of, 253 Oxidation, disease and pathogenesis associated with, 29 Oxidative stress, 15–16 antioxidative stress food factors, 16 chronic disease and, 23 defined, 5, 15 endogenous antioxidative stress mechanisms, 16 exogenous protein/peptide antioxidants, 16

Index

Oyster, antioxidant peptides and GI digests of, 33 P Pain, nitric oxide levels and, 56 Pain management, transdermal route of administration and, 360 Pan, A., 68 Pan, Y., 158 Pancreatic elastase, in BIOPEP database, 332 Papain, 171 Papain hydrolysates, high molecular weight peptides in, 275 Parasites, lactoferrin and, 187 Parenteral route of administration for biopharmaceuticals, difficulties related to, 360 Parkinson’s disease, 90 alpha-synuclein and, 92 amyloid deposits and, 89 gamma-aminobutyric acid and, 124 nitric oxide levels and, 56 peptidomics and, 319 Parotha (oily flat bread), rice bran proteins in, 239 Pastries, antioxidant caseinophosphopeptides in, 35 Pasupuleti, V. K., 74 Pathogenesis, oxidation and, 29 Pattern-recognition receptors, 18 PBPCs. See Rice bran protein concentrates PCA. See Principal component analysis PCR. See Polymerasae chain reaction PCT-SPS. See Pressure Cycling Technology Sample Preparation System PDGF. See Platelet-derived growth factor Peanut allergy model, 113 Pea protein-derived cationic peptide fractions effect of, on intrinsic fluorescence of Ca2+/CaM-dependent protein kinase, 63, 63t

inhibition of CaM-dependent protein kinase II activity by, at varying CaM levels, 62, 62t Pea protein-derived peptides as calmodulin inhibitors, 62–64 increases in Fmax/Fo values for CaMKII interactions and, 60 Pea protein hydrolysates, enzymatic, free radical (DPPH)-scavenging activity of, 275 Peas angiotensin-I converting enzyme inhibitory effects of, 280–281 anticancer effects due to Bowman-Birk protease inhibitors, 278–280 antimicrobial effects due to peptides, 281–284 antimicrobial peptides from garden pea, 281–282 chickpeas, 283 commercial utilization potential of, 283–284 cowpeas, 282–283 antioxidant effects with, 274–275 bioactivity of proteins and peptides from, 9 hypocholesterolemic effects of, 275–278 Pedroche, J., 280 Pelagic thresher, ACE inhibitory peptides isolated from, 208 Pellegrini,A., 251 Pellet cooker, rice bran stabilization and, 235 Pellet mill, rice bran stabilization and, 235 Penetratin, 192 Peng, X., 35 Pentadecapeptide (gramicidin D), 361 Pentadin, 351 Pentane, 214 Pentosans, 233 PEPCK. See Phosphoenolpyruvate carboxylase kinase

407

Pepsin, 154, 171 in BIOPEP database, 332 PepT1, 140 Peptide antioxidants, exogenous, 16 PeptideAtlas, 311 Peptide-based immunotherapy advantages of, 110–111 aim and rationale for, 108 B-cell epitope-based immunotherapy, 110 current experimental models of, in food allergy, 111–114 cow’s milk allergy model, 112–113 egg allergy model, 113–114 inhalant allergens, 114 peanut allergy model, 113 wheat and beef allergy model, 114 food allergies and, 7, 102 food-based hydrolyzates, 109–110 strategies for, 108 suggested mechanisms underlying, 111 T-cell epitope-based immunotherapy, 110 translation of, into human clinical applications, 114–115 large-scale production of peptides, 115 MHC polymorphism, 115 use of overlapping synthetic peptides, 109 Peptide-based vaccines, practical issues relative to, 115 Peptide hormones, 307 Peptide libraries, 107 Peptide mass fingerprinting, 336 Peptide precursors, 328 Peptides. See also Amyloidogenic proteins and peptides; Antihypertensive peptides; Anti-inflammatory proteins and peptides; Antioxidant peptides; Antioxidative stress proteins and peptides antimicrobial proteins and, from eggs, 249–254 avidin, 254 egg cystatin, 254

408

Index

Peptides (continued) lysozyme, 250–251 ovalbumin, 252–253 ovomacroglobulin, 253 ovomucin, 253 ovotransferrin, 252 phosvitin, 253–254 antioxidant, 16–17 assessing radical-scavenging property of, 35 barriers and mechanism of bioavailability of, 366–379 binding of metal ions by, 37 bioactive, production of, 154–155 bitter taste and spatial arrangement of, 347 classes of, 361 controlled delivery of, 360 designed, 93t enzymatic release of, with antithrombotic and antiamnestic activity and control of gastric mucosal function, 332, 334t exogenous, examples of those exhibiting antioxidant activity in vitro and in model systems: sources and sequences, 37t flavor ingredients interacting with, 352–353 identification of, 314–315 immunomodulating, 254–255 large-scale production of, 115 liquid crystalline systems and entrapment and stability of, 360–366 novel, peptidomics and, 320 within nutraceutical food sector, 5 physico-chemical properties related to bitterness of, 345, 347 plethora of research on, 354 potential correlation between bitterness and bioactive properties of, 348–349 predicting bitterness of, 347–348 production of, from food sources, 344 from proteins, benefits with, 325

quantification of, 315–316 release of, from milk proteins, 332 separation, 313–314 size and bitterness of, 345, 347 synthetic, food allergy and use of overlapping, 109 taste-activating properties of, 344–345, 347–351 taste-active, development of, 355 therapeutic, 359 Peptide sequences, for calmodulin-binding peptides isolated from peptic hydrolysate of bovine casein and potency against phosphodiesterase I, 57t Peptide soup, 171t Peptide synthesis, automated, 115 Peptide therapeutics, improving delivery of, 10 Peptide transporters, 140 Peptide transport system, 265 amino acids transport system and, on small intestine cell, 266 Peptidic compounds, preventing amyloid formation and, 94–95 Peptidomics (or “peptide proteomics”) applications of, 317–320 peptide biomarkers in disease, 318t, 319 peptides and diet-disease associations, 318t, 319–320 peptides as biomarkers, 317–319, 318t peptides in regulation of behavior, 318t, 320 peptidomics and novel peptides, 318t, 320 for bioactive peptide analysis, 307–320 defined, 10, 307 methods in, 308–311 affinity peptidomics, 308–309 combinatorial peptidomics, 309 mass spectrometry, 309–311 methods of, 308

sample preparation for, 311–317 enrichment and detection of proteins useful to peptidomic studies, 312–313 method validation, 317 peptide identification, 314–315 peptide quantification, 315–316 peptide separation, 313–314 posttranslational modifications, 316–317 sample collection and preanalytical treatment, 311–312 steps in sample preparation for, 312 Peptidyl antioxidants, as multifunctional compounds, 30 PeptoPro, 163t Pepys, M. B., 88t Pericarp, 233 Permeability of macromolecules, increasing, technologies for, 360 Peroxyl radicals, 29 Peroxynitrite, 29 Pessi, T., 20t Pet care supplements, bLf added to, 193 Petersen, W. E., 156 PHA. See Phytohaemagglutinin Phagocytes, lactoferrin and activation of, 188 Pharmaceutical Research and Manufacturers of America, 359 Pharmacological applications, lysozyme used in, 251 Phe, 45 Phenolic antioxidants, 215 Phenolic compounds in flaxseed, 58 preventing amyloid formation and, 9294 Phenylalanine, 274 bitterness associated with, 343 Phifer, C. B., 144 Phormones, 326

Index

Phosphatidylcholine, hypocholesteremic effect of legume protein and, 276 Phosphatidylethanol-amine (PE) ratio, of liver microsomes, hypocholesteremic effect of legume protein and, 276 Phosphodiesterase I, 56 calmodulin-binding peptides isolated from peptic hydrolysate of bovine casein and potency against, 57t Phosphoenolpyruvate carboxylase kinase, 142 Phosphopeptides, 326 Phosvitin antimicrobial properties of, 253–254 antioxidant activity of, 256 in egg yolk, 248 Phosvitin phosphopeptides, 17, 17t, 18 Physical instability processes, protein and peptide drug inactivation with, 365 Phytantriol, two-photon fluorescence images showing lateral distribution of sulphorhodamine B, after 24 hours of passive diffusion in skin and, 377 Phytantriol cubic phase, summary of fluorescent features observed in two-photon microscopy images at various tissue depths of skin exposed to sulphorhodamine B in, 378t Phytic acid, in germinated brown rice, 126 Phytochemicals, 30 Phytohaemagglutinin, 21 Phytonutrients, bitter taste in, 342 Pichon, L., 137 Picrotin, 342 Piglet development, Lfcin and Lfampin chimeras and, 194 Pig skin gelatin, preparing, 205 Pisavin, 282 Pisumin, antifungal activity of, 282

PIT. See Peptide-based immunotherapy Pittaway, J. K., 276 Pituitary hormones, angiotensin II and, 207 Plant development, gamma-aminobutyric acid and, 123–124 Plant food allergens, structural superfamilies of, 105 Plant phenols, 215 Plant proteins anti-inflammatory mechanisms and, 23 antioxidant activity of, 216 antioxidative stress proteins and peptides in, 18 bioactive peptides and, 332, 334 Plants metabolic pathway in, 127 roles of GABA synthesis in, 122–124 Plant serine protease inhibitors, structurally distinct families of, 278 Plant sources of foods, 105 Plasma amino acids, as central satiety signals, 142–143 Plasmin, 171 Plasmodium falciparum, lactoferrin’s effects against, 186 Platelet-derived growth factor, in bovine mammary secretions, 152, 161 Playford, R. J., 161 Pleurotus ostreatus, sativin’s antifungal activity against, 282 PLP-dependent enzymes, reaction mechanism of GAD and, 127 PMF. See Peptide mass fingerprinting Pneumonia, lactoferrin and, 188 Pokeweed (PW) mitogen, 21 Polaprezinc anti-inflammatory activity of, 227 ulcer healing and, 228

409

Polar headgroup interaction, hydrophilic and lipophilic pathways of drug interaction and, 368, 369 Poliovirus, lactoferrin’s antimicrobial activity and, 158 Polisb, rice kernel, 234 Poly-enzymatic method, for reducing bitterness of protein hydrolysates, 350 Polymerase chain reaction, 311 Polymeric glutenins, elastic property of, 9–10 Polymorphonuclear cells, 19 Polyomvirus, lactoferrin’s effects against, 185 Polyphenol compounds, inhibitory mechanism of amyloid fibril formation by, 94 Polyphenols, bitter taste in, 342 Polyphosphates, bitterness masked with, 350 POMC. See Pro-opiomelanocortin POMC neurons, food intake and activation of, 144 Popel, A. S., 318 Pore-forming peptides, increasing skin permeability for transdermal delivery and, 373, 379 Pork gelatin, producing gelatin from fish to match gelling properties of, 219 Port protein, 216 Posttranslational modifications, 316–317 Potatoes antioxidant proteins/peptides in, 17 “wound-induced” inhibitors I and II in, 278 Potato protein, antioxidant activity of peptides in, 34 PPPs. See Phosvitin phosphopeptides Praventin, 163t Precipitation, protein and peptide drug inactivation with, 365

410

Index

Precursor proteins number of fragments with antithrombotic, antiamnestic, and regulating stomach mucosal membrane activity released from, 334t in silico, enzymes releasing bioactive peptides from, 335–336t PREDICT 7 application, 326 Pregerminated brown rice, GABA used in, 129 PREMIER clinical trial, on soy protein and blood pressure, 80 Pressure Cycling Technology Sample Preparation System, 311 Preventative medicinal chemistry, 6 Primary amyloidosis, 90 Principal component analysis, predicting bitterness of peptides and, 348 Prion diseases, 89, 90 amyloid deposits and, 89 identifying, 90 Prion elk, 93t Prion human peptide, 93t Prion mouse, 93t Prion protein, 88t, 90 Prion Syrian hamster, 93t Pripp, A. H., 349 Pro, 45 Probiotic bacteria, commercial, bioactive peptide production and, 155 Pro calcitonin, 88t Procaspase-3 activation, lactoferrin and, 190 ProDiet F200/Lactium, 163t ProDom, 326 “Prodrug” peptides, 354 Prolactin, 88t Prolamin, 290, 291–293, 295 Proline ACE inhibitory activity, bitterness and, 348 radical quenching activity of peptides and, 35 sweet and bitter taste of, 343

Proline endopeptidase, 332 Proline oligopeptidase, in BIOPEP database, 332 Pronase, 332 Pro-opiomelanocortin, 143 Propanol, 214 Prophylactic effect, 113 Propyl gallate, 214, 215 Prorenin, 207 PROSITE, 326 Protease/amylase mixture, rice bran protein extraction and, 236 Protease inhibitors, in eggs, 258 Protein animal muscle as valuable source of, 225 Atwater factor for, 142 cereal, 234 Protein antioxidants, exogenous, 16 Proteinase K, 171, 332 Protein-based therapeutics, physico-chemical and biological properties and delivery challenges with, 359–360 Protein-derived antioxidants in food systems, evaluation of, 34–35 Protein diet, weight loss and, 136 Protein hydrolysates antioxidant efficacy of, 38 assessing antioxidant activity of peptides in, 34 bitter peptides of, isolated by different researchers, 346–347t bitter taste in, 342 debittering approaches for, 349–351 flavor ingredients interacting with, 352–353 peripheral, gut-derived satiety hormones and, 139–140 physico-chemical properties related to bitterness of, 345, 347 plethora of research on, 354 production of, from food sources, 344

satiety triggering and, 136, 144–145 taste-activating properties of, 344–345, 347–351 Protein hydrolysis, bitter taste and, 345 Protein in diet, metabolic syndrome and, 68 Protein-induced satiety and food intake inhibition, 7, 136–144 central neuronal pathways and, 143–144 energy expenditure and glucose as metabolic signals in, 142 high-protein diets and, 137–138 high-protein preload and highprotein meal-induced satiety and food intake inhibition, 136–137 peripheral, gut-derived satiety hormones, 139–142 plasma amino acids as central satiety signals, 142–143 role of protein source and type in, 138–139 Proteins, 105. See also Amyloidogenic proteins and peptides; Anti-inflammatory proteins and peptides; Antioxidative stress proteins and peptides antioxidant, 16–17 antioxidant peptides in, 32 barriers and mechanism of bioavailability of, 366–379 bitter peptides of, isolated by different researchers, 346–347t in bran, 233 classification of, 290, 361 into families and subfamilies, 328, 336 controlled delivery of, 360 in eggs, 247, 249, 258 in egg yolk, 248 factors related to nutritional quality of, 203 fish, 204 flavor ingredients interacting with, 353–354

Index

free radical attacks on, 29 immunomodulating, 254–255 in silico analysis of, 326–328, 331 interaction between sweet-taste receptors and, 351–352 in large eggs, 249 liquid crystalline systems and entrapment and stability of, 360–366 plethora of research on, 354 profiles of potential biological activity of, 337 richest subfamilies of–precursors of peptides with selected activities, 329–331t strategy for research on, 327, 327 sweet, 351 taste-active, development of, 355 taste-active properties of, 351–352 interaction between proteins and sweet-taste receptors, 351–352 sweet proteins, 351 taste-modifying property of sweet proteins, 352 therapeutic, 359 Protein sequences, BIOPEP database and motifs with 23 types of activity in, 328 Protein solubility, role of, in processed foods, 237 Protein therapeutics, improving delivery of, 10 Proteolysis in silico, release of bioactive peptides from selected precursor proteins by enzymes or enzyme conjugates and, 331–332, 334 Proteolysis simulation example, in BIOPEP database, 333 Proteolytic enzymes bioactive peptides and, 162 BIOPEP data on, 331 Proteomic techniques, use of, 154 Proteose peptone-3, 20t anti-inflammatory mechanisms and, 20t, 22

Protozoans, Lfcin’s effects on, 192 PrP. See Prion protein PRRs. See Pattern-recognition receptors Psd1, 282 Psd2, 282 Pseudomonas aeruginosa, lactoferrin’s antimicrobial activity and, 158 Pseudomonas spp., ovotransferrin’s effect against, 252 PT cubic phase, GMO cubic phase vs., in hydrophilic fluorescent model drugs investigation, 379 PTMs. See Posttranslational modifications p21 protein, lactoferrin-induced overexpression of, 190 Pungent foods, 342 Purification, of bioactive milk proteins, 153 Puroindolines, 291 Q Q-ion-trap (Q-IT), 310 QSAR. See Quantitative structure and activity relationship QSAR modeling, ACE inhibitory activity, bitterness and, 349 Q-TOF, 310 Quantitative structure and activity relationship, 257, 258 development of functional ingredients and, 354 predicting peptide bitterness and, 347–348 Quark, bioactive peptides and, 161 Quercetin, 92 Q values, bitterness of peptides and, 345 R Rainbow trout fibroblasts, metallo-collagenase MMP-13 isolated from, 205 Rajapakse, N., 37t, 217t Ramipril, 174, 208 Ramputh, A. R., 123

411

RAS. See Rennin-angiotensin system RB. See Rice bran RBDPs. See Rice bran dehydrin proteins RBEE. See Rice bran enzymatic extract RBL. See Rice bran lectin RBPIs. See Rice bran protein isolates Rb promoters, lactoferrin and, 190, 191 RBPs. See Rice bran proteins RDA. See Recommended daily allowance RDI. See Recommended daily intake Reactive oxygen species, 5, 29, 163 defined, 15 GI diseases and, 32 lactoferrin and, 188 production of, 16 Reaven, G. M., 67 Recombinant hLf, antimetastatic effects with, 189 Recommended daily allowance, 248 Recommended daily intake, 249 Red wheat, 290 Regnier, F., 315 Regular Iletin I, aggregation profiles of, 365, 365 Regular Iletin II, aggregation profiles of, 365, 365 Regulatory T cells, food allergy and, 103 Rehault, S., 249t Reidelberger, R. D., 139 Reiter, B., 159 Ren, J., 217t Renin, 207, 298 Renin-angiotensin, circulatory, updated, 45 Renin-angiotensin system, 45 blood pressure regulation and, 207, 298 hypertension and, 44 inhibition of, by ACE inhibitory peptides, 46–47 Reperfusion injury, oxidative stress and, 31–32

412

Index

Residual proteins, in cereal, 235 Resistin, 70, 71 Retino-blastoma protein-mediated growth arrest, lactoferrin and, 190 Retinoid signaling pathways, lactoferrin and, 190 Retronasal contributions, to aroma perception, 354 Reverse hexagonal phase, delivery of proteins and peptides and, 360 Reverse osmosis, manufacture of whey powder and whey protein concentrates and, 153–154 Reverse phase strong cation exchange cartridge system, 318–319 Rheumatoid arthritis, lactoferrin’s anti-inflammatory role in, 187 rhLf. See Recombinant hLf Rhodobacter sphaeroides, 361 Rhodopsin/transducer complex, 361 Rhus verniciflua Stokes glycoprotein, anti-inflammatory mechanisms and, 20t, 23 Ribosome inactivating proteins, 282 Rice, production and milling of, 233 Rice-based vaccine, efficiency of, 115 Rice bran composition of, 233, 234t defatted, proximate composition and caloric content of, 234t enzymes isolated from, 238 future trends with, 242–243 protein provided by, 234 stabilization of, 234–235 Rice bran dehydrin proteins, functional properties of, 237 Rice bran enzymatic extract, 239 Rice bran lectin, 241–242 Rice bran protein concentrates, functional properties of, 237 Rice bran protein isolates, functional properties of, 237

Rice bran proteins, 234 amino acid composition of, 240t antinutritional behavior of, 242 extraction and isolation of, 235–237 alkali extraction, 236 enzymatic extraction, 236 miscellaneous methods, 236–237 functional properties of, 237–238 health benefits of, 240–242 as antioxidants, 242 lectins, 241–242 in prevention and control of cancers, 241 human health promotion and, 8–9 in product development, 238–242 in animal feeds, 239 in baby foods, 239 in bakery products, 239 as fat replacers, 239–240 as flavor enhancers, 238–239 as food-color carriers, 239 in meat products, 239 miscellaneous applications, 240 as substrate for microbial growth, 240 Rice bran proteolysate, 237 Rice cultivators, proteins consecutively solubilized with water, salt, alcohol, acetic acid, and sodium hydroxide from ether-defatted brans of, 235 Rice flour, composition of, 234t Rice kernel, parts of, 234 Righetti, P. G., 313 RIPs. See Ribosome inactivating proteins Ririe, D. G., 227 Riticum aestivum amino acid sequence of low-molecular-weight glutenin subunit in, 295 amino acid sequence of x-type high-molecular-weight glutenin subunit in, 294 amino acid sequence of y-type high-molecular-weight glutenin subunit in, 294

Rival, S. G., 37t RNase, 93t RO. See Reverse osmosis Rolls, R. J., 136 Ropelle, E. R., 143 ROS. See Reactive oxygen species Rosmarinic acid, 92 Rotaviruses immune milk preparations and, 156 lactoferrin’s antimicrobial activity and, 158 lactoferrin’s effects against, 185, 186 Roufik, S., 162 Round scad antioxidant peptides from, 217t antioxidative activity of hydrolysates from, 218 RP-SCX cartridge system. See Reverse phase strong cation exchange cartridge system rTI1B, 278, 278t rTI2B, 278, 278t Rukimini, C., 241 RVS glycoprotein. See Rhus verniciflua glycoprotein S S. enteriditis, lactoferrin’s antimicrobial activity and, 158 S. flexneri, lactoferrin and, 186 Saccharin, 351 Saccharomyces cerevisiae, ACE inhibitory peptides isolated from, 172 S-adenosyl methionine, hypocholesterolemic effects of pea proteins and, 277 Sadhale, Y., 365, 366 Saito, K., 37 Saito, M., 267 Saito, Y., 173 Sake, ACEI peptides in, 173 Sake lee, ACEI peptides in, 173 Salicin, 342 Salmon ACE inhibitory peptides derived from, 210t

Index

ACI inhibitory peptides derived from, 208 hypotensive effects of, in spontaneously hypertensive rats, 213t Salmonella enteritidis, ovotransferrin’s effect against, 252 Salmonella typhimurium, lactoferrin’s antimicrobial activities and, 158, 185 “Salting-out” effect, liquid crystalline phases and, 362 Salt-soluble globulin, 290 Salty taste, 10, 342 dipeptides and, 345 triggering of, 342 SAM. See S-adenosyl methionine Sarcoplasmic proteins, in fish proteins, 204 Sardine, ACE inhibitory peptides derived from, 209t, 210t Sardine muscle, hypotensive effects of, in spontaneously hypertensive rats, 213t Sardine peptide, 44, 44t Sathivel, S., 217t, 218 Satiation/satiety, 135 brain’s response to retronasal aroma release and, 354 complex and complementary pathways and mediation of, 145 defined, 135 egg breakfasts vs. bagel breakfasts and, 248 food intake inhibition in high-protein diets and, 137–138 high-protein meal-induced, high-protein preload and, 136–137 luminal events within GI tract and, 138 plasma amino acids as central signals in, 142–143 protein-induced, 7 central neuronal pathways and, 143–144

energy expenditure and glucose as metabolic signals in, 142 role of protein source and type in, 138–139 Satiety hormones, peripheral, gut-derived, 139 Sativin, antifungal activity of, 282 Savory peptides, in foods, 344 Savory taste, 343 Sawai, Y., 125 SAXS patterns. See Small angle x-ray scattering patterns SBEAMs architecture, 311 SBP. See Systolic blood pressure SCD-1. See Stearoyl-CoA desaturase Schiff-base, formation of, by substrate and PLP, 128 Schiff-base exchange reaction, PLP enzymes and, 127 Schulz-Knappe, P., 314 Scrutton, H., 157 SD-RBPs. See Spray-dried rice bran proteins SDS. See Sodiumdodecyl sulfate SDS-PAGE, 237 Sea bream ACE inhibitory peptides derived from, 208, 210t hypotensive effects of, in spontaneously hypertensive rats, 213t “Search for active fragments” icon, in BIOPEP, 332 Secondary amyloidosis, 90 Selenium, 215, 225 Semenogelin I, 88t Semolina, 289 Sensitization phase, in allergic response to food antigens, 103 Sensory profile of food, amino acids and, 344 Sensory rhodopsin, 361 Septicemia, 194 Septic shock, lactoferrin and prevention of, 187 Serine, 37 collagenases, 205 in fish gelatin, 206 sweet taste of, 343

413

Serpell, L. C., 89 Serpins, 291 Serum lipids, soy protein and, 76, 79 Sesame peptides, 44 Sesamine tea, 171t Severe Acute Respiratory Syndrome, 194 Shah, J. C., 365, 366 Shahidi, F., 217t Shanghai Women’s Health Study, 79 Shell eggs, 247 Shellfish antioxidant peptide production in GI system and, 33 antioxidant peptides from, 217t branched amino acids present in antioxidant peptides from, 216 Shigella dysenteriae, lactoferrin’s antimicrobial activities and, 185 Shigella flexneri, immune milk preparations and, 156 Shin, K., 20t Short-term preload paradigm, 136 SHRs. See Spontaneously hypertensive rats Sick fat, 71 SISCAPA. See Stable Isotope Standards and Capture by Anti-Peptide Antibodies SIT. See Specific immunotherapy Sites, C. K., 78t Skarra, L., 353 Skeletal muscle, oxidative deterioration of, 225 Skim milk, large-scale preparation of bLf from, 193 Skin allergy, lactoferrin and, 187, 188 Skin barrier, pathways of drug penetration across, 368, 368 Skin penetration, time course of percutaneous delivery of CysA incorporated in cubic and hexagonal liquid crystalline phases, with olive oil control, 369–370, 370

414

Index

Skin permeability biochemical enhancers and increase in, for transdermal drug delivery, 373 fluorescein and measurements of, 374, 374 magainin peptides and, 373–376 Skip-jack tuna ACE inhibitory peptides derived from, 209t Indonesian dried-salted, ACE inhibitory activity exhibited by, 211 Skp1 promoters, lactoferrin and, 190, 191 Sleep regulation, gamma-aminobutyric acid and, 125 Sletten, K., 88t Small angle x-ray scattering patterns, 363, 364 Small peptides amyloidogenicity of, 92 antihypertensive mechanism of, 46–51 inhibition of renin-angiotensin system by ACE inhibitory peptides and, 46–47 relaxation of vascular constrictive events by dipeptides and, 48–51 effect of, on Ang II stimulation or Bay K 8644 stimulation, 48, 48 Smeets, A. J., 136, 141 Smoking cessation, transdermal route of administration and, 360 Smooth hound (shark), antioxidant peptides from, 217t SOD. See Superoxide dismutase Sodiumdodecyl sulfate, hydrophobicity of insoluble glutelins and, 25 Sodium sterate, hydrophobicity of insoluble glutelins and, 235 Sodium substitutes, 345 Sole, antioxidant peptides from, 217t Soleimanpour, M. R., 265

Solubilization, of rice bran proteins, 235 Somatic and testicular ACE, 211 Son, D. O., 227 Sour milk, bioactive peptides and, 161 Sour taste, triggering of, 343 Soy anti-inflammatory mechanisms and, 22–23 di- and tri-enriched peptides developed from, 266 Soybean paste, ACEI peptides in, 173 Soybean protein, antioxidant activity of, 216 Soybeans, typical industrial processing of, 69 Soybean seedlings, GABA used in, 129 Soymilk, GABA content and, 126 Soy peptide ingestion, comparison of placebo, soy protein, and soy peptide on GH and CPK levels measured at 30 minutes and 18 hours after, 268 Soy peptides antiobesity effect of, 268–269 antioxidant activities related to, 17 di- and tri-enriched peptides from soy and, 266 efficacy of on lipid metabolism compared with soy protein, 267–269 in sports, soy protein vs., 267 as functional food system, 265–269 health promotion and, 9 manufacturing process for, 266 peptide transport system, 265 production of, 267 Soy proteins antioxidant acitivty of peptides in, 34 effects of animal protein and, on body fat ratio of obese rat and genetically obese mice, 269

efficacy of soy peptides in sports, soy proteins vs., 267 flavor ingredients interacting with, 353 health benefits with, 68, 81 high demand for, 239 lipid metabolism and efficacy of soy peptides vs., 267 for metabolic syndrome, 6, 67–81 blood pressure and, 79–80 glycemic control and insulin resistance, 74–76 reduction of caloric intake, 74 serum lipids and, 76, 79 weight loss and adiposity reduction, 71, 72t, 73–74 soy peptides prepared from, 9 Soy sauce, inhibitory activities in, 172 Specific immunotherapy, food allergy and, 108 Spellman, D., 350 Spices, natural antioxidants in, 215 Spielmann, J., 276 Spontaneously hypertensive rats, 8, 155, 170 ACE-inhibitory fish peptides and, 212–214 evaluating antihypertensive activity of ACEI peptides in, 173 hypotensive effects of fish-derived peptides in, 213t ovokinin’s effects in, 257 stroke-prone, ACE activity in aorta of, 174 Sports, soy peptides vs. soy protein and, 267 Sprague-Dawley (SD) rat aorta rings, carnosine relaxation effect in, 49 Spray-dried rice bran proteins, 237 Spring wheat, 290 SPS. See Stiff-person syndrome SP-sepharose, 58 Squid, ACE inhibitory peptides derived from, 210t SRB. See Sulphorhodamine B SREBP-1. See Sterol regulatory element-binding protein-1

Index

SREBP-2. See Sterol regulatory element-binding protein-2 SREBPs. See Sterol regulatory element binding proteins SSADH. See Succinic semialdehyde dehydrogenase SS31 peptide, antioxidant activity and, 31, 31t Stable Isotope Standards and Capture by Anti-Peptide Antibodies, 314 Staphylococcus aureus lactoferrin’s antimicrobial activity and, 158 ovotransferrin’s effect against, 252 Staphylococcus spp., lactoferrin’s antimicrobial activities and, 185 Starchy endosperm, rice kernel, 234 STC-1 cells, 140 Stearoyl-CoA desaturase, soy protein and, 79 Stemplot analysis, 328, 336 Sterol regulatory element-binding protein-1, soy protein and, 79 Sterol regulatory element-binding protein-2, 276 Sterol regulatory element binding proteins, soy protein and, 71 Stiff-person syndrome, 124 Stimulating site, 347 St-Onge, M. P., 78t Stratum corneum permeation of, by drug molecules, 367–368 in vitro penetration of CysA in, at 6 and 12 hours following topical application using hexagonal phase nanodispersion or control olive oil formulation, 372 water content in, 368 Streptococcus mutans immune milk preparations and, 156 lactoferrin’s antimicrobial activity and, 158

lysozyme effect against, 251 ovotransferrin’s effect against, 252 Streptococcus spp. GABA biosynthesis with, 126 lactoferrin’s antimicrobial activities and, 185 Streptococcus thermophilus, lactoferrin and, 194 Streptokinase, 360 Stress food factors, antioxidative, 16 Stress relief, alpha-lactalbumin and, 156–157 Stroke, nitric oxide levels and, 56 Subcutaneous route of administration, for biopharmaceuticals, 360 Subtilisin, 154, 171 Succinic semialdehyde dehydrogenase, 127, 128, 129 Succinyl-1-proline, 207 Sucralose, 351 Sucrose, 351 Suetsuna, K., 208, 209t Sugiyama, K., 276 Sulphorhodamine B chemical structure of, 376 summary of fluorescent features observed in two-photon microscopy images at various tissue depths of skin exposed to using different vehicles, 378t transdermal study of, using four delivery systems, 376–377 two-photon fluorescence images showing lateral distribution of, after 24 hours of passive diffusion in skin using four delivery systems, 377 Sunde, M., 89 Sunflower oil, amino acids with antioxidant activity in, 216 Supercritical water, rice bran protein extraction and, 237 Superoxide anion, 29 Superoxide dismutase, 16, 256

415

Suppressor T cells. See Regulatory T cells Surface adsorption, protein and peptide drug inactivation with, 365 Surface nucleolin, lactoferrin binding and, 186 Sweet proteins, 351, 352 Sweet taste, 10, 342 peptides with, 344 triggering of, 342 Sweet-taste receptors, interaction between proteins and, 351–352 SWISS-PROT, 326 Syndrome X. See Metabolic syndrome Synthetic antioxidants, 215 Synthetic peptides, overlapping, food allergy and, 109 Synthetic vaccines, 359 Systemic amyloidosis, 90 Systolic blood pressure, ovokinin and, 257 T T. gondii, lactoferrin’s effects against, 186 Tagging-via-substrate approach, for global identification of O-glycosyl enrichment, 314 Tamaru, S., 268 Tammen, H., 318 Tanaka, M., 95 Tancredi, T., 351 TAS approach. See Tagging-viasubstrate approach Taste, synergistic interactions with effect on, 344 Taste-active properties of peptides and protein hydrolysates approaches for debittering or production of less bitter protein hydrolysates, 349–351 physico-chemical properties related to bitterness of, 345, 347

416

Index

Taste-active properties (continued) potential correlation between bitterness and bioactive properties of peptides, 348–349 prediction of bitterness in peptides, 347–348 of proteins, 351–352 interaction between proteins and sweet-taste receptors, 351–352 sweet proteins, 351 taste-modifying property of sweet proteins, 352 Taste characteristics, of amino acids, 343–344 Taste modalities, 10, 342 Taste receptor cells, 342–343 Tau, 88t Tau, 93t Taurine, in animal muscle, 225 Taylor, A. A., 49 Taylor, C. G., 31t TBARS. See Thiobarbituric acid reactive substances T-cell epitope-based immunotherapy food allergy and, 110 potential mechanisms underlying, 112 T-cell epitopes antigen, representation of, 106 food allergen, 105–106 mapping, 106–107 T-cell receptors, 106 T-cell regulation, currently accepted view on, 105 T cells, allergic responses and, 105 TCRs. See T-cell receptors Tea antioxidant caseinophosphopeptides in, 35 GABA and, 125 natural antioxidants in, 215 Telomere shortening, carnosine protective against, 228 Tempeh, antioxidant peptides in, 38 Testa, 233 Textural profile analysis, 239

TGF-beta, food allergy and, 104, 116 TGF-beta1, in bovine mammary secretions, 152, 153, 161 TGF-beta2, in bovine mammary secretions, 152, 153, 161 THAA. See Total hydrophobic amino acids content Thaumatin, 351 T helper cell (ThO), food allergy and, 103 Therapeutic effect, 113 Therapeutic macaromolecules, oral administration of, difficulties related to, 360 Therapeutic proteins and peptides, 359 Thermal-processing, rice bran stabilization and, 235 Thermogenesis, diet-induced by protein, 142 Thermolysin, 154, 171 Thiansilakul, Y., 217t Thiobarbituric acid reactive substances, 34 THM. See Tsukuba-Hypertensive Mouse Thomas, D. A., 31t Th1 response, lactoferrin and, 188–189 Th1/Th2 cytokine balance, lactoferrin and, 188 Th1/Th2 model, food allergy and, 103 Threonine, 37, 343 Th17 cells, 105 Thymus-derived Tregs, food allergy and, 104 Tissue array technology, 311 Tityus serrulatus venom peptides, identifying, 320 TLR4. See Toll-like receptor 4 TLRs. See Toll like receptors T-lymphocytes food allergy and roles of, 103–105 lactoferrin and, 188 TMAB. See Trimethylammoniumbutyrate TNBS. See Trinitrobenzenesulfonic acid

Tobacco smoke, reactive oxygen species and, 16 Tofu, fermented, inhibitory activities in, 172 Togawa, J., 20t “Tolerance” induction, food allergy and, 108 Tolerogenicity, hypoallergenicity vs., 112–113 “Tolerogenic” peptides, 108 Toll-like receptor 4, lactoferrin and, 187 Toll like receptors, 18 Tomato, “wound-induced” inhibitors I and II of, 278 T1R2-T1R3 receptors, proteins and, 351–352 Total hydrophobic amino acids content, antioxidant effects from peas and, 274 Toxoplasma gondii, Lfcin’s effects on, 192 TPA. See Textural profile analysis TPM. See Two-photon microscopy Transcellular route of administration, across stratum corneum, 368, 368 Transdermal route of administration, for biopharmaceuticals, 360 Transepidermal route of administration across stratum corneum, 368 divisions of, 368 for permeation of stratum corneum by drug molecules, 367–368 Transfollicular route of administration, across stratum corneum, 368 Transforming growth factor, in bovine mammary secretions, 152, 161 Transglandular route of administration, across stratum corneum, 368 Transthyretin, 88t TRCs. See Taste receptor cells Tregs, food allergy and, 103, 104–105 Treharose, 95

Index

TrEMBL, 326 Tremblay, F., 75 Tricitum sphaerococcum, 290t Triglycerides metabolic syndrome and levels of, 68t soy protein and, 76 Tri-glycine peptides, absorption of, 265 Trimethylammoniumbutyrate, 316 Trinitrobenzenesulfonic acid, in rats, anti-inflammatory effect of GMP and, 21 Tripeptide ACE inhibitors, 212 Tripeptides antioxidant properties and, 37 development of, from soy, 266 intestinal adsorption of, 174 release of, from milk proteins, 332 Triplet repeat disease, 92 Triticum aegilopoides, 290t Triticum aestivum, 289, 290, 290t amino acid sequence of alpha-amylase inhibitor in, 291 amino acid sequence of alphabeta-gliadin in, 292 amino acid sequence of y-gliadins in, 292 Triticum compactum, 289, 290, 290t Triticum dicoccoides, 290t Triticum dicoccum, 290t Triticum durum, 289, 290, 290t Triticum macha, 290t Triticum monococcum, 290t Triticum orientale, 290t Triticum polonicum, 290t Triticum spelta, 290t Triticum turgidum, 290t Triticum urartu, 290t Triticum vavilovii, 290t Tritrichomonas foetus, lactoferrin’s effects against, 185 Tropomyosin, in myofibrillar tissue proteins, 204 Troponin, in myofibrillar tissue proteins, 204 Trp, 17, 45

Trp-His schematic representation of binding site to voltage-gated L-type Ca2 channel in VSMC, 52 vascular relaxation profiles of, in endothelium-intact (+) or endothelium-denuded Sprague-Dawley rat aorta rings, 51 Trypanosoma brucei, lactoferrin’s effects against, 185 Trypanosoma cruzi, lactoferrin’s effects against, 185 Trypsin, 154, 171, 250 in BIOPEP database, 332 Bowman-Birk inhibitors and, 278t identification of selected biopeptides released by, from milk proteins, 334, 336 Trypsin hydrolysates, 275 Tryptic hydrolysates, of casein, 43, 44t Tryptophan, 274 ACE inhibitory activity, bitterness and, 348 radical quenching activity of peptides and, 35 Tsukuba-Hypertensive Mouse, 46 Tsushida, T., 125 TR family, of bitter receptors, 343 Tumorigenesis, lactoferrin as defense against, 189, 190 Tumor necrosis factor-alpha, 18, 19, 187, 188 Tumor suppressor proteins, lactoferrin acting as, 191 Tuna ACE inhibitory peptides derived from, 208, 209t antioxidant peptides from, 217t hypotensive effects of, in spontaneously hypertensive rats, 213t Twin-screw extruder, rice bran stabilization and, 235 Two-dimensional electrophoresis, investigating bioactive peptide proteins with BIOPEP database and, 336

417

2-D-methylsuccinyl-1-proline, 207 Two-photon microscopy, transdermal studies and use of, 376, 377, 377, 379 Type I diabetes, 298 Type II diabetes, 71, 75, 298 Tyr, 17, 45 Tyrosine, 29, 274 antioxidant activity of peptides and, 216 bitterness associated with, 343 food intake and, 142, 143 radical quenching activity of peptides and, 35 Tyr-Val, vascular relaxation effect of, in 18-week-old SHR thoracic aorta rings constricted by 30 mmol/L KCI, 49 U U. S. Department of Agriculture Foreign Agriculture Service, 9 UCPs. See Uncoupling proteins UDN. See Ulmus davidiana Nakai UF. See Ultrafiltration Ulcers, carnosine and healing of, 228 Ulmus davidiana Nakai, anti-inflammatory mechanisms and, 20t, 23 Ultrafiltration fractionation of bioactive peptides and, 155 manufacture of whey powder and whey protein concentrates and, 153–154 Umami taste, 10, 342, 343 glutamate and, 344 peptides with, 344 triggering of, 342 Uncoupling proteins, soy protein and, 74 United States, rice bran production in, 233 U.S. Department of Agriculture, Foreign Agricultural Service, 289 U.S. Food and Drug Administration, 115, 129, 159

418

Index

USDA. See U. S. Department of Agriculture UV radiation, reactive oxygen species and, 16 V Vaccines, synthetic, 359 Vagal afferent pathways, protein sensing and signalling to brain and, 144 Valenti, P., 249t Valine ACE inhibitory activity, bitterness and, 348, 349 bitterness associated with, 343 Valio (Finland), 170 Val-Pro, antihypertensive effects of, in spontaneously hypertensive rat, 173 Val-Pro-Pro, 162, 172 absorption of, 174 antihypertensive effect of milk tested in hypertensive patients, 173 casein hydrolyzate with, 170 hypotensive capacity of, 155 Val-Tyr with ACE inhibitory activity, 171 antihypertensive effects of, in spontaneously hypertensive rat, 173 change in systolic blood pressure and ACE activities of 18-week-old spontaneously hypertensive rat after administration of, 47 inhibition of renin-angiotensin system and, 46–47 regulation of vascular events by dipeptides and, 47–48 vascular relaxation effect of, in 18-week-old SHR thoracic aorta rings constricted by 30 mmol/L KCI, 49 Vascular constrictive events, dipeptides and, 47–51 Vascular smooth muscle cell, 47 Trp-His binding site to volatge-gated L-type Ca2 channel in, 52

“Vectors of Hydrophobic, Steric, and Electronic,” predicting bitterness of peptides and, 348 Vegetable oils, amino acids with antioxidant activity in, 216 Vegetable proteins, hypocholesterolemic effects of, 275–278 Vegetables, natural antioxidants in, 215 Vegetable sources of foods, 105 Ventromedial nucleus, satiety and, 143 Verbeek, M. M., 88t Verma, D. D., 371 Vermeirssen, V., 281 Very-low-density lipoproteins, 71, 276 VHSE. See “Vectors of Hydrophobic, Steric, and Electronic” Vibrio cholerae, lactoferrin’s antimicrobial activities and, 158, 185 Vibrio parahaemolyticus, halophilic, Lfcin and Lfampin chimeras and, 194 Vickers, Z., 141 Vidal, R., 88t “View the report with the results” option, in BIOPEP, 332 Virchow, Rudolf, 89 Virtanen, T., 39 Viscozyme, 237–238 Visfatin, 70 Vitamin C, 30 Vitamin E, 30 Vitamins, 215 from animal muscle, 225 in bran, 233 Vivinal Alpha, 163t VLDL. See Very-low-density lipoproteins VMN. See Ventromedial nucleus VSMC. See Vascular smooth muscle cell W Wagner, J. D., 74 Wako, Y., 210t

Walleye pollack antioxidant peptides from, 217t antioxidative activities of enzymatic hydrolysates from, 218 Wang, D., 38 Wang, H. F., 125 Wang, H. X., 282 Wang, L., 320 Wang, Y. F., 80 Ware, J. H., 20t Watanabe, K., 249t Water, as penetration enhancer, 368 Water channels, drug rate of transfer and size of, 373 Water-soluble albumin, 290 Water-soluble oryzanol enzyme extract, antioxidative function of, 242 Water-soluble proteins and peptides, properties of liquid crystalline phases and, 362 Water vehicle summary of fluorescent features observed in two-photon microscopy images at various tissue depths of skin exposed to sulphorhodamine B and, 378t two-photon fluorescence images showing lateral distribution of sulphorhodamine B, after 24 hours of passive diffusion in skin and, 377 WDEIA. See Wheat-dependent exercise-induced anaphylaxis Wei, C., 37t Weighted holistic invariant molecular index descriptors, predicting bitterness of peptides and, 348 Weight loss eggs and, 248 gamma-aminobutyric acid and, 125 high-protein meals and diets and, 145 soy protein’s effect on, 71, 72t, 73–74, 77–78t sustained high-protein diet and, 136

Index

Weight management, whey proteins and, 152 Weight reduction, high-protein diets and, 68 Westermark, P., 88t, 91 Westerterp-Plantenga, M. S., 137 Wheat classification of, 289–290 families of alpha-amylase inhibitors in, 298 grain color of, 290 major cultivated species of, 289, 290t rice protein net protein utilization compared to, 240 sowing seasons for, 290 world-wide production and consumption of, 289, 290 Wheat albumin, 291, 298 Wheat allergy, 295–298 baker’s asthma, 295, 296, 299 celiac disease, 295, 297, 299 reduction of, 297–298 symptoms of, 295–296 types of, 295 wheat-dependent exercise-induced anaphylaxis, 295, 296–297, 299 Wheat allergy model, 114 Wheat-dependent exercise-induced anaphylaxis, 10, 295, 296–297, 299 Wheat gliadin, antioxidant activity of, 216 Wheat peptides, hypertension prevention and, 298–299 Wheat production, cereal production and, 9 Wheat protein antioxidant acitivty of peptides in, 34 classification of, 290–295 albumin, 291 glutelin (glutenin), 293, 295 gluten, 295 prolamin (gliadin), 291–293 epitope structure of, 297 Whey, health-promoting proteins and peptides in, 7–8

Whey powder, membrane separation processes and, 153–154 Whey protein hydrolysate, gel filtration of OH signals for samples containing different peptide fractions, 36 Whey protein isolates, gel filtration and, 154 Whey proteins antioxidant acitivty of peptides in, 34 beneficial health effects with, 155–156 bioactive in bovine colostrum and milk, 153t occurrence and isolation of, 152–154 biological functions and applications of, 155–160 alpha-lactalbumin, 156–157 beta-lactoglobulin, 157 glycomacropeptide, 160 immunoglobulins, 156 lactoferrin, 157–159 lactoperoxidase, 159–160 concentrates of, membrane separation processes and, 153–154 functional peptides in, 171 glutathione concentrations in, 18 health benefits in, 151–152 increase in GLP-1 concentrations in casein vs., 141 membrane separation processes and, 153–154 membrane system to produce and separate antioxidant peptides from, 38 WHIM descriptors. See Weighted holistic invariant molecular index descriptors White kidney bean (Phaseolus vulgaris), antioxidant effects of, 274 White wheat, 290 Wine production, lysozyme used in, 251 Winter wheat, 290

419

Wolosiak, R., 274 World Health Organization, 255, 298 Worobiej, E., 274 Wound healing, muscle-based dipeptides and, 228 WPI. See Whey protein isolates WSOEE. See Water-soluble oryzanol enzyme extract Wu, H. C., 217t Wu, J., 249t. Y Yamashita, H., 296 Yang, H., 320 Yang, Y., 276 Ye, X. Y., 282, 283 Yeast prion sup35, 93t Yeasts, Lfcin and inhibition of, 192 Yellowfin sole ACE inhibitory peptides derived from, 208, 210t antioxidant peptides from, 217t Yellowfin sole frame protein, 211 Yellowfin sole frame protein hydrolysates, 216 Yellowfin sole protein, branched amino acids present in antioxidant peptides from, 216 Yellowsole, hypotensive effects of, in spontaneously hypertensive rats, 213t Yellow stripe trevally antioxidant peptides from, 217t antioxidative activity of protein hydrolysates from, 218 Yemenicioglu, A., 274 YFPHs. See Yellowfin sole frame protein hydrolysates Yogurt bioactive peptides and, 155, 161 GABA concentration in, 126 Yokoyama, K., 209t Yolk of egg, major proteins in, 248 Yoshikawa, M., 209t, 213t Yust, M. M., 280

420

Index

Z Zein, 290 antioxidant peptides and in vitro digests of, 32–34

reducing, metal chelation, and ABTS scavenging activity of, in vitro digests, 33 Zimecki, M., 20t, 159

Zinc, 215 Zinc ion, active site of ACE and, 212 Zittel, T. T., 144