Peptides in Food and Health

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Peptides as Functional Foods and Nutraceuticals

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

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A John Wiley & Sons, Inc., Publication

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Peptides as Functional Foods and Nutraceuticals

Yoshinori Mine, Eunice Li-Chan, and Bo Jiang EDITORS

A John Wiley & Sons, Inc., Publication

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Blackwell Publishing was acquired by John Wiley & Sons in February 2007. Blackwell’s publishing program has been merged with Wiley’s global Scientifi c, Technical, and Medical business to form Wiley-Blackwell.

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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 specifi cally disclaim all warranties, including without limitation warranties of fi tness 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

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• Advances in Dairy Ingredients (Geoffrey W. Smithers and Mary Ann Augustin)

• Biofi lms in the Food Environment (Hans P. Blaschek, Hua H. Wang, and Meredith E. Agle) • Calorimetry and Food Process Design (G ö n ü l Kaletun ç )

• 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 - Fran ç ois 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 - C à novas, 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 Benefi ts (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 - Modifi ed Oils in Foods (Frank T. Orthoefer and Gary R. List)

• Water Activity in Foods: Fundamentals and Applications (Gustavo V. Barbosa - C à novas, Anthony J. Fontana Jr., Shelly J. Schmidt, and Theodore P. Labuza)

• Whey Processing, Functionality and Health Benefi ts (Charles I. Onwulata and Peter J. Huth)

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vii

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-infl ammatory/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

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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

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ix

Functional proteins and peptides are now an important category within the nutraceuticals food sector.

A growing body of scientifi c evidence in the past decade has revealed that many food proteins and peptides exhibit specifi c 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 fi elds 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 fi eld, which made the publication of this book possible. We believe that this book deserves a broad readership in the disci- plines 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 com- ments 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

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xi

Icy D ’ Siva

Department of Food Science University of Guelph

Guelph, ON, Canada N1G 2W1 Bart ł omiej 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 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

Imelda W.Y. Cheung

The University of British Columbia Food Nutrition & Health Program 2205 East Mall

Vancouver, BC, Canada V6T 1Z4

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Nissim Garti

[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 Gonz á lez de Mej í a

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

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

Guelph, ON, Canada N1G 2W1 Hitomi Kumagai

College of Bioresource Sciences Nihon University

[email protected] - u.ac.jp Phone/Fax: +81 - 466 - 84 - 3946 Dominique Legrand

Unit é de Glycobiologie Structurale et Fonctionnelle

Universit é des Sciences et Technologies de Lille UMR No. 8576 du CNRS / IFR 147

F - 59655 Villeneuve d ’ Ascq Cedex, France dominique.legrand@univ - lille1.fr

Phone: 33 - 3 - 20 - 43 - 44 - 30; Fax: 33 - 3 - 20 - 43 - 65 - 55 Yanhong Li

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 Eunice.Li - [email protected]

Phone: 1 - 604 - 822 - 6182; Fax: 1 - 604 - 822 - 5143

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Yuki Maeda

8304 Minamiminowamura Ina, Nagano 399 - 4598, Japan Kaustav Majumder

Edmonton, AB, Canada T6G 2P5 Cristina Mart í nez - 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] - u.ac.jp Phone: +81 - 92 - 642 - 3012 Jo ë l Mazurier

F - 59655 Villeneuve d ’ Ascq Cedex, France Yoshinori Mine

Guelph, ON, Canada N1G 2W1 [email protected]

Phone: 519 - 824 - 4120 x52901; Fax: 519 - 824 - 6631 Wanmeng Mu

Wuxi, Jiangsu 214122, China

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

8304 Minamiminowamura Ina, Nagano 399 - 4598, Japan Wokadala C. Obiro

Wuxi, Jiangsu 214122, China Takanobu Owaki

8304 Minamiminowamura Ina, Nagano 399 - 4598, Japan Annick Pierce

F - 59655 Villeneuve d ’ Ascq Cedex, France Myl é ne Potier

AgroParisTech

Life Sciences and Health 16 rue Claude Bernard 75005 Paris, France

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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 Tom é AgroParisTech

Life Sciences and Health 16 rue Claude Bernard 75005 Paris, France Jianping Wu

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

Guelph, ON, Canada N1G 2W1 Denise Young

Guelph, ON, Canada N1G 2W1 Tao Zhang

Jiangnan University

Wuxi, Jiangsu 214122, China

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Introduction

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5

Biologically Active Food Proteins and Peptides in Health: An Overview

Yoshinori Mine , Eunice C.Y. Li - Chan , and Bo Jiang

A growing body of scientifi c evidence in the past decade has revealed that many food proteins and peptides exhibit specifi c biological activities in addition to their established nutritional value (Mine and Shahidi 2006 ; Hartmann and Meisel 2007 ; Tripathi and Vashishtha 2006 ; Yalcin 2006 ; M ö ller 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 benefi ts claimed for protein nutraceuticals were based on in vitro models or limited clinical trials leading to equivocal fi nd- ings (M ö ller et al. 2008 ). Technological and fundamental problems remain in relation to large - scale production, compatibility with different food matri- ces, gastrointestinal stability, bioavailability, and long - term safety (Murray and FitzGerald 2007 ; Mine 2007 ). Research into consumer perception and

legislation is also necessary. Nutritionists, biomedi- cal 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 benefi ts. 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, specifi c 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 - infl ammatory 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

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since clinical evidence demonstrated the effi cacy 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 purifi cation of cationic peptides. Inhibition of CaM - dependent enzymes seems to be dependent mostly on the level of basic (positively charged) amino acid residues for short - chain ( < 7 - mer) peptides, whereas long - chain (16 - to 25 - mer) peptides interact with CaM mostly through hydrophobic interactions.

Structural changes occur during peptide binding, leading to an increased unfolding of CaM such that the protein loses its ability to effectively interact with and activate target metabolic enzymes. It is evident that food protein – derived CaM - binding peptides constitute a potential source of ingredients that may be used to formulate therapeutic diets against human chronic diseases. However, the ultimate utility of these cationic peptides will depend on their oral bioavailability and in vivo inhibition of target metabolic reactions.

Chapter 6 describes the potential for soy protein to address the problem of metabolic syndrome (MS).

Diets with increased protein and reduced carbohydrates have been shown to improve body composi- tion and lipid and lipoprotein profi les, reducing blood pressure and playing a part in regulation of glucose and insulin homeostasis, all of which are factors associated with treatment of metabolic syndrome and obesity. Soy protein is a promising dietary component that needs to be further evaluated in regards to its long - term effect on adipogenesis and potential reduction of blood pressure. This will allow determination of the recommended intake of soy protein to reduce the risk of metabolic syndrome in humans from different backgrounds and environments.

Attention must also be paid to the technological processes in order to optimize the protein quality, its bioavailability, and the main protein components that will produce the most biologically active peptides.

infl ammation 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 infl uence specifi c biological activities such as oxidative stress and infl ammation. As our understanding of the effi cacy and mechanism of action of antioxidative stress and anti - infl ammatory 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 effi cacy of peptide intake for borderline hypertensives is evidentially developed on the basis of extensive intervention trials, but such an effective foods for specifi ed 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 fi elds in preventative medicinal chemistry,

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most investigations. Elucidation of the mechanisms underlying PIT has guided research into further understanding of allergic responses, which may lead the way toward the design of more effi cient immu- notherapeutic approaches.

Gamma - aminobutyric acid (GABA), a four - car- bon nonprotein amino acid, is a signifi cant component of the free amino acid pool in most prokaryotic and eukaryotic cells. Chapter 9 highlights the recent updated applications of GABA for food and human health. GABA was discovered fi rst in potatoes more than half a century ago and subsequently in rat brains. GABA has many biological functions such as neurotransmission and induction of hypotensive, diuretic, and tranquilizer effects. GABA production by various microorganisms has also been reported using bacteria, fungi, and yeast.

Food intake in man is determined by both physiological and psychological factors. All factors are centrally received, organized, and integrated balanc- ing both short - term and long - term energy intake with energy expenditure. The regulation of energy intake is determined by both the energy content and the energy source (fat, carbohydrate, and protein) of the meal, each of them having unique effects on satiation and satiety regulatory mechanism. Chapter

10 describes food - derived peptides as regulators of satiety. This chapter centers on protein - induced satiety, in particular focussing on mechanisms and regulation of protein - induced satiety. The evidence derived from studies with different experimental models with animals and humans is given, emphasis on the underlying biochemical and neural mechanisms.

Chapter 11 deals with health - promoting proteins and peptides in colostrum and whey. The high nutritional value of bovine milk proteins is widely recognized. Also, the multiple functional properties of major milk proteins are well characterized and exploited by various industries. Over the last 2 decades, milk proteins have attracted growing scientifi c and commercial interest as a source of biologically active molecules having distinct characteristics. The best characterized bioactive bovine whey proteins include immunoglobulins (Igs), lactoferrin (Lf), lactoperoxidase (LP), and growth

Chapter 7 deals with amyloidogenic proteins and peptides. To date, many different naturally occurring proteins and polypeptides have been recognized to be amyloidogenic in humans. These precursor proteins, clearly differing in their biochemical function and in their three - dimensional structure, may become prone to undergoing an irreversible transition from their native conformation into highly ordered amyloid fi brils. The extracellular deposition of amyloid fi brils in tissues is the basis of a wide range of human diseases, including neurodegenerative disorders of the central nervous system and various forms of systemic and cutaneous amyloidosis. Under certain conditions, soluble proteins and protein fragments (peptides) self - assemble into β - sheet - rich structures (cross - β conformation) and form amyloids. These amyloids can cause serious disorders known as amyloidosis such as Alzheimer ’ s disease, hemodialysis - associated disease, and bovine spon- giform encephalopathies, which are characterized by the transformation of soluble proteins/peptides into aggregated fi brils in different organs and tissues. Recent reliable discovery of amyloid - forming sequences in amyloidogenic proteins should have a great impact on the development of antiamy- loid agents.

Food allergy is classically defi ned as an adverse reaction to food components resulting from an overt response mediated by the immune system. Its prevalence has been estimated at 2 – 4% of adults and 6 – 8% of children in Western countries. These fi gures would represent approximately twice those reported only a decade ago. Chapter 8 summarizes recent advances on peptide - based immunotherapy (PIT) for food allergy. Peptide - based immunotherapy has been praised as a promising strategy for food allergy by a number of reviews. While PIT investigations carried out with inhalant allergens have reached clinical settings with encouraging results, there is currently little information on the curative potential of PIT in food - induced allergies.

However, recent PIT investigations using murine models of food allergy point the way toward promising avenues. Of the various strategies proposed, an immunotherapy based on the use of T - cell epitope - containing peptides has been, to date, the object of

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that is expressed in most biological fl uids and is a major component of the innate immune system of mammals. Its protective effect ranges from direct antimicrobial activities against a large panel of microorganisms including bacteria, viruses, fungi, and parasites to anti - infl ammatory and anticancer activities.

Chapter 14 focuses on bioactive peptides and proteins from fi sh muscle and collagen. As marine fi sh supplies are threatened due to excessive fi shing and poor management, the need to obtain fi sh protein from sustainable sources like aquaculture and improved processing has increased. Post - harvest losses, as discards at sea, deterioration during storage, and wastage during processing, are substan- tial. Therefore utilizing and upgrading waste from fi sh processing into valuable food products is a major goal. Like mammalian muscle proteins, fi sh myofi brillar proteins display excellent gelation and emulsifying properties. In the last decade, fi sh collagen from skin and bones has been used to produce gelatin. This chapter reviews hydrolysates and peptides from fi sh muscle and collagen and their ACE inhibitory and antioxidant activity that may lead to their applications as bioactive ingredients in functional foods, conventional foods, and neutraceuticals.

Muscle - based bioactive peptides have been shown to possess many health benefi ts and are therefore also promising candidates as nutraceutical or functional food ingredients. Since meat and meat products are important in the diet in most developed countries, functional meat products would contribute to human health. The biological activities of muscle - based peptides are summarized in Chapter

15 . Further studies will be required to demonstrate the clear benefi ts of muscle - derived bioactive peptides and their potential nutraceutical applications to benefi t human health.

Chapter 16 describes recent technology and value - added utilization of rice bran proteins (RBPs) and their peptides for human health promotion.

Cereals are the most widely grown crops of the world and the kernel or caryopsis consists of bran, embryo, and endosperm. The bran is composed of fi bers (pentosans, hemicelluloses, β - glucans, factors. They occur in colostrum in much higher

concentrations than in milk, refl ecting their impor- tance to the health of the neonate. These native proteins are known to exert a wide range of physiological activities, for example, enhancement of nutrient absorption, stimulation of cell growth, enzymatic activity, inhibition of enzyme activity, modulation of the immune system, and defense against microbial infections. At present, milk proteins are considered the most important source of bioactive peptides. Over the last decade a great number of peptide sequences with different bioac- tivities have been identifi ed in various milk proteins.

The best - characterized milk peptides exhibit antihypertensive, antithrombotic, antimicrobial, antioxidative, immunomodulatory, and opioid activities.

Chapter 12 reviews antihypertensive peptides originating from fermented milk products and enzymatic hydrolysis of food proteins, such as milk casein whey proteins and fi sh meat. Most antihypertensive peptides with proven effects on spontaneously hypertensive rats have angiotensin I – converting enzyme inhibitory activities. Clinical experiences for these antihypertensive peptides were also reviewed to discuss the potential of antihypertensive peptides for high blood pressure. Studies reporting an in vivo mechanism, based mainly on animal studies, were also described. The benefi ts of antihypertensive peptides with ACE inhibitory activities generated from food proteins were introduced. Some of the peptides with antihypertensive effects in spontaneously hypertensive rats (SHR) demonstrated signifi cant effi cacies in humans. In Japan, some ACE inhibitory peptides with proven signifi cant antihypertensive effects in humans have been approved as FOSHU products (functional food products) with health claims concerning high blood pressure.

Taking into account the mild effects of ACE inhibitory peptides, which have no adverse effects, they may be considered to be ideal food - derived natural functional ingredients to keep blood pressure within the normal range.

Chapter 13 summarizes our knowledge of the structure and biological functions of lactoferrin and of peptides derived from it. Lactoferrin is an iron - binding glycoprotein of the transferrin family

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extensively for lipid - lowering effect in humans and in experimental animals. Although soy protein contains a certain amount of bioactive peptides that have distinct physiological activities in lipid metabolism, it is not clear that peptides are responsible for these effects. This chapter describes the nutritional benefi ts and the biochemical function of soy peptides. Soy peptides prepared from soy protein could well serve as an excellent nutritional supplement with improved absorption properties. The ingestion of soy peptides decreases the muscle damage induced after exercise and shows double effective- ness as compared with soy protein. On the other hand, it was revealed that soy peptides stimulate hypolipidemic events and accelerate antiobesity effects. It is important to conduct more research on active components in the future. Soy peptides may have the ability to prevent some lifestyle diseases.

Chapter 19 presents bioactivity of proteins and peptides from peas ( Pisum sativum, Vigna unguiculata, and Cicer arietinum L ). Legumes are important sources of dietary proteins. There has been increased interest in their benefi cial effects in terms of several health claims that are professed.

This chapter reviews recent studies on the nutraceutical/pharmaceutical/therapeutic biological activities of proteins and peptides from legumes commonly referred to as peas (chick peas, Cicer arietinum ; garden/green peas, Pisum sativum ; and cow peas, Vigna unguiculata ).

Chapter 20 introduces wheat proteins and peptides. World wheat production accounts for about 30% of world cereal production, being about 587 million tons in 2006, according to the annual report of the United States Department of Agriculture (USDA) Foreign Agricultural Service. Wheat production and consumption are the highest in the European Union (EU) countries, followed by China and India. Wheat is a major crop that is consumed all over the world in the form of various products such as pasta, bread, cakes, and cookies. The quality of wheat products is affected by protein content because the viscoelastic property of gluten allows dough to expand during heating and provides fi rm texture to pasta after boiling. This characteristic of gluten is mainly attributed to the elastic property of cellulose, lignin, and glucofructans), ash, enzymes,

vitamins, and storage proteins. The various fractions of rice bran such as oil, carbohydrates, and dietary fi bers ( β - glucans, phytates, tannins), and RBPs have demonstrated their ability in prevention of diseases.

Some of them are found to have potent anticancer and antioxidant activity. Some of the second - generation by - products of rice bran, that is, RBP concen- trates and isolates, show tremendous potentials for future industrial utilization in view of their multifac- torial functionality, including their medicinal value.

The residual proteins being of high molecular weight and with considerable water - binding capacity may be used as hydrocolloids, which have demonstrated health benefi ts in improving lipid profi le, controlling hyperglycemia, and lowering glycemic index of foods.

Chapter 17 summarizes recent advances of bioactive egg proteins and peptides. Nature forms an avian egg not for human food but to produce a chick.

Birds invest in the reproductive process up front, transferring all the nutrients and energy needed to allow the embryo to reach the point of hatching.

This concentration of highly available nutrients also makes the egg an ideal nutritional food source; eggs are one of the few foods that are consumed throughout the world. Recent studies have uncovered various roles of egg proteins that go well beyond their basic nutrient value. Indeed, egg proteins may gain increasing recognition in the future in human health, as well as in disease prevention and treatment. However, this value can only be captured through the development of industrially viable technologies that are essential for successfully harvest- ing valuable egg components for commercial use.

Lysozyme and antibody technologies are two such examples of extracted components. Eggs contain more than 60 various types of proteins. The pres- ence of biologically active proteins, especially minor egg proteins, has raised interest in developing novel agents from eggs against chronic diseases, such as cancer.

The potential for developing novel bioactive peptides deserves further study. Chapter 18 focuses on soy peptides as functional food materials. Soy protein is one of the vegetable proteins examined

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properties. The emergence of new peptides from various sources necessitated the creation of a database and the establishment of additional criteria for assessing the value of proteins as precursors of bioactive peptides. The BIOPEP database of proteins and bioactive peptides was developed in 2003.

Bioinformatics methods applied in biotechnology and biochemistry are becoming increasingly popular due to short waiting times for results, low testing costs, the option of recording results in the form of text fi les, and, consequently, the recover- ability of results, and they continue to be improved as new advances are made in the fi eld of information technology. With the increasing demand for incor- porating functional proteins and peptides into food ingredients, natural health products, and dietary supplements to enhance health, it is crucial to examine the fl avor - active properties of these components that may infl uence their acceptance by con- sumers. Three of the fi ve basic taste modalities that are currently recognized, namely sweet, salty, and umami, have historically been associated with foods that contain nutrients important for human health and well - being — energy containing carbohydrates (sweet), essential minerals (salty), and amino acids (umami). Chapter 23 explores the fl avor - active properties of amino acids, peptides, and proteins that must be considered for successful incorporation and acceptance of components with biologically active properties as ingredients in natural health products, nutraceuticals, and functional foods.

The protein and peptide therapeutics have become an important class of drugs due to advancement in molecular biology and technology. However, an effective and convenient delivery of these drugs in the body remains a challenge. Over the last 10 years, extensive studies have been carried out to improve their delivery. Yet there are still a number of limita- tions due to their intrinsic physicochemical and biological properties, including poor permeation through biological membranes (due to large molecular size), short half - life, physical and chemical insta- bility, enzymatic catalysis, aggregation, adsorption, bio - incompatibility, and immunogenicity. Chapter

24 presents the diffi culties in delivery of proteins polymeric glutenins and the plasticizing property of

gliadins. Glutelins and gliadins each account for about 40 – 46% of total protein, having unique amino acid sequences that are rich in glutamine and proline residues. Although the amount of albumin is not high, it contains amylase inhibitor that inhibits amylase activity and retards carbohydrate digestion, preventing the increase in postprandial hyperglycemia. However, amylase is resistant to proteolysis by digestive enzymes and may be a cause of allergies such as baker ’ s asthma. On the other hand, gliadins sometimes become a cause of wheat - dependent exercise - induced anaphylaxis (WDEIA) and coeliac disease. As epitopes in gliadins for WDEIA and coeliac disease are comprised of glutamine - rich tandem repeat motifs, the cleavage or modifi cation of the motifs is effective to reduce their allergenicity.

Some peptides, such as Ile - Ala - Pro from wheat ab - gliadin and Ile - Val - Tyr from wheat germ, prevent hypertension by inhibiting ACE. Wheat proteins have various functions. Science needs to be developed to maximize their favorable functions, such as prevention of diabetes and hypertension, and to minimize their adverse functions, such as allergenicity.

Peptidomics can be defi ned as the comprehensive multiplex analysis of endogenous peptides contained within a biological sample under defi ned conditions to describe the multitude of native peptides in a biological compartment. Peptidomics or “ peptide proteomics ” refers to the analysis of all the peptides of a cell or tissue (peptidome), while proteomics refers to the analysis of the proteins (pro- teome). Chapter 21 presents an overview of the advances in peptidomics and applications of peptidomics for discovering novel bioactive proteins and peptides in food and nutrition research.

Chapter 22 highlights in silico analysis of bioactive peptides. Research conducted by numerous scientifi c centers around the world has contributed to the identifi cation and description of a vast number of biologically active peptides isolated from the body tissues and fl uids of many organisms, including bacteria, fungi, plants, and animals. Biologically active peptides are the recommended ingredients of functional food, that is, food designed with the aim of generating the desired functional and biological

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Hartmann R , Meisel H . 2007 . Food - derived peptides with biological activity: From research to food applications . Curr Opin Biotechnol 18 ( 2 ): 163 – 169 .

Korhonen H , Pihlanto A . 2007a . Technological options for the production of health - promoting proteins and peptides derived from milk and colostrum . Curr Pharm Des 13 ( 8 ): 829 – 843 . Korhonen H , Pihlanto A . 2007b . Bioactive peptides from food

proteins . In: YH Hui , ed., Handbook of Food Products Manufacturing: Health, Meat, Milk, Poultry, Seafood, and Vegetables , 5 – 38 . Hoboken, NJ : John Wiley & Sons . Meisel H . 2005 . Biochemical properties of peptides encrypted

in bovine milk proteins . Curr Medical Chemistry 12 : 1905 – 1919 .

Mine Y . 2007 . Egg proteins and peptides in human health - chemistry, bioactivity and production . Curr Pharm Des 13 : 875 – 884 .

Mine Y , Miyashita K , Shahidi F . 2009 . Nutrigenomics and Proteomics in Health and Diseases: Food Factors and Gene Interactions . Ames, IA : Wiley - Blackwell .

Mine Y , Shahidi F . 2006 . Nutraceutical Proteins and Peptides in Health and Disease . New York : CRC - Taylor & Francis . M ö ller NP , Scholz - Ahrens KE , Roos N , Schrezenmeir J . 2008 .

Bioactive peptides and proteins from foods: Indication for health effects . Eur J Nutr 47 ( 4 ): 171 – 182 .

Murray BA , FitzGerald RJ . 2007 . Angiotensin converting enzyme inhibitory peptides derived from food proteins:

Biochemistry, bioactivity and production . Curr Pharm Des 13 ( 8 ): 773 – 791 .

Tripathi V , Vashishtha B . 2006 . Bioactive compounds of colostrum and its application . Food Reviews Intl 22 : 225 – 244 . Yalcin AS . 2006 . Emerging therapeutic potential of whey pro-

teins and peptides . Curr Pharm Des 12 : 1637 – 1643 .

and peptides and discusses the liquid crystal – based controlled delivery systems that were produced and examined to improve delivery.

In summary, the collection of chapters in this book, written by an international team from industry and academia, provides a comprehensive overview of the fundamental concepts, mechanisms, and ongoing research needs, as well as current and pro- spective applications, of the major categories of biologically active proteins and peptides with potential for signifi cant benefi ts to human health. It is hoped that the knowledge and insights gained from these chapters will pave the way to realizing the tremendous opportunities within this rapidly growing fi eld of bioactive proteins and peptides from food sources as nutraceuticals and functional foods.

References

Boelsma E , Kloek J . 2009 . Lactotripeptides and antihypertensive effects: A critical review . Br J Nutr 101 ( 6 ): 776 – 786 . Gilani GS , Xiao C , Lee N . 2008 . Need for accurate and standard-

ized determination of amino acids and bioactive peptides for evaluating protein quality and potential health effects of foods and dietary supplements . J AOAC Intl 91 ( 4 ): 894 – 900 . Gobbetti M , Minervini F , Rizzello , CG . 2007 . Bioactive peptides

in dairy products . In: YH Hui , ed., Handbook of Food Products Manufacturing: Health, Meat, Milk, Poultry, Seafood, and Vegetables , 489 – 517 . Hoboken, NJ : John Wiley & Sons .

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Functions of Biologically Active Proteins and Peptides

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15

Anti - infl ammatory/Oxidative Stress Proteins and Peptides

Denise Young and Yoshinori Mine

Contents

1. Oxidative Stress, 15

1.1. Endogenous Antioxidative Stress Mechanisms, 16

1.2. Exogenous Protein/Peptide Antioxidants, 16

1.3. Antioxidative Stress Food Factors, 16 2. Antioxidant Proteins and Peptides, 16 3. Antioxidative Stress Proteins and

Peptides, 17

3.1. Egg Yolk Peptides, 17

3.1.1. Phosvitin Phosphopeptides, 17 3.2. Milk Protein, 18

3.3. Plant Proteins/Herbal Medicine, 18 3.3.1. Gardenia jasminoides Glycoprotein, 18 4. Oxidative Stress and Infl ammation, 18 4.1. Infl ammation, 18

4.1.1. Cell Signaling Mechanisms Associated with Infl ammation, 19

5. Anti - infl ammatory Proteins and Peptides, 19

5.1. Egg Proteins, 19 5.1.1. Lysozyme, 19 5.1.2. Ovotransferrin, 19 5.2. Milk Peptides, 19 5.2.1. Bovine Casein, 19

5.2.2. Glycomacropeptide/ κ - caseinoglycopeptides, 21

5.2.3. Lactoferrin, 21 5.2.4. Proteose Peptone - 3, 22 5.3. Soy, 22

5.3.1. Trypsin Inhibitors, 22

5.4. Plant Proteins/Herbal Medicine, 23 5.4.1. Ulmus davidiana Nakai Glycoprotein, 23 5.4.2. Rhus vernicifl ua Stokes Glycoprotein, 23 6. Conclusion, 23

7. References, 23

1. Oxidative Stress

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. Reactive oxygen species are a type

of free radical that is formed with oxygen. Free radicals are chemical substances that contain one or more unpaired orbital electrons and are therefore unstable and liable to react with other molecules to form more stable compounds with a lower energy state. In an attempt to achieve this stable state, ROS react with proteins, lipids, and DNA, which can result in damage and inactivation of cellular components such as enzymes, membranes, and DNA (Halliwell and Cross 1994 ; Valko et al. 2004 ). As such, ROS and oxidative stress as a whole have been

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1.2. Exogenous Protein/

Peptide Antioxidants

Antioxidant activities of peptides are defi ned by characteristics such as linoleic acid peroxidation, reducing activity, free radical scavenging, active - oxygen quenching, metal - ion chelation, and per- oxynitrite scavenging. In essence it encompasses all the physical, nongenetic interactions that can occur between the antioxidative compound and the oxidants. The purpose of these exogenous antioxidants is to neutralize the antioxidant or prevent/minimize further oxidative reactions.

1.3. Antioxidative Stress Food Factors Recently, food - derived compounds like curcumin and fl avonoids and olive oil biophenols have been shown to upregulate intracellular GSH synthesis (Biswas et al. 2005 ; Myhrstad et al. 2002 ) and increase GPx and GR antioxidant enzyme activities (Yang et al. 2005 ). Similarly, antioxidative stress peptides include peptides associated with the induction of endogenous antioxidants such as glutathione and the phase 2 enzymes. These antioxidant defense systems present in mammalian cells evolved to protect cells against oxidative and electrophilic damage. SOD catalyzes the dismutation of O2i− to form hydrogen peroxide (H 2 O 2 ). Since H 2 O 2 is cell - permeable and toxic, it is quickly converted to water (H 2 O) by catalase or GPx. GPx oxidizes the enzyme cofactor GSH to oxidized glutathione (GSSG) during the decomposition of H 2 O 2 . GSSG can be reduced to GSH by GR. GSH is also required as a cofactor for GST in the detoxifi cation of organic hydroperoxides and electrophiles. The coordinate actions of these molecules are highly effective in oxidant and electrophilic cellular detoxifi cation, therefore the induction/upregulation of these oxidants and enzymes by bioactive peptides is an area of growing interest.

2. Antioxidant Proteins and Peptides Although antioxidant peptides are not the focus of this chapter, a few examples are given in broad suggested to participate in the initiation and/or prop-

agation of chronic diseases such as cardiovascular and infl ammatory diseases, cancer, and diabetes (Valko et al. 2004 ).

ROS can be produced on a regular basis during oxidative metabolism and in more potent levels during infl ammation. During oxidative metabolism, electrons are lost from the electron transport chain and combine with oxygen, resulting in the formation of superoxide anion ( O2i−) (Boveris and Chance 1973 ). At the time of infl ammation, innate immune cells produce and release ROS to destroy invading microorganisms (Rosen et al. 1995 ). Environmental factors such as tobacco smoke, ultraviolet radiation, overexertion during exercise, and the consumption of alcohol and certain foods can also result in the generation of ROS (Bunker 1992 ; Powers and Jackson 2008 ). The consumption of antioxidants and foods that infl uence endogenous antioxidative stress mechanisms can play a role in limiting the proliferation of ROS, thereby re - establishing a stable redox balance.

1.1. Endogenous Antioxidative Stress Mechanisms

Aerobic organisms can increase production of biochemical antioxidants such as glutathione (GSH) and induce endogenous antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx) to inactivate oxidants, forming instead biologically inert products (Cimino et al. 1997 ; Halliwell 1990 ). GSH ( γ - glutamylcysteinylglycine) is the major nonenzymatic regulator of redox homeostatis and is ubiquitously present in all cell types (Meister and Anderson 1983 ). It can directly scavenge free radicals or act as a substrate for GPx and glutathione S - transferase (GST) during detoxifi cation of hydrogen peroxide, lipid hydroperoxides and electrophilic compounds. Glutathione is synthe- sized in two sequential adenosine triphosphate – dependent reactions catalyzed by γ - glutamylcysteine synthetase ( γ - GCS) and glutathione synthetase (GS) (Griffi th 1999 ).

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soy peptides, enzymatic hydrolysates from wheat germ protein (Zhu et al. 2006 ) and alpha - and beta - lactoglobulin (Hern á ndez - Ledesma et al. 2005 ) have been identifi ed as possessing antioxidant and free radical – scavenging activities. Antioxidant proteins and peptides have also been identifi ed in egg (Sakanaka and Tachibana 2006 ), potato (Wang and Xiong 2005 ), and gelatin (Park et al. 2005 ). A detailed account of other antioxidants can be found in Elias ’ s review (Elias et al. 2008 ) of antioxidative proteins and peptides.

3. Antioxidative Stress Proteins and Peptides

Proteins and peptides with antioxidative stress properties can be derived from a variety of food sources including egg, milk, and plant. Table 2.1 summarizes these bioactive components and their mechanism of action.

3.1. Egg Yolk Peptides

3.1.1. Phosvitin Phosphopeptides Hen egg yolk phosvitin is a highly phosphorylated protein with 10% phosphorus (Taborsky 1983 ) monoesterifi ed to 57.5% serine (Ser) residues (Allerton and Perlmann 1965 ). Oligophosphopeptides prepared from egg yolk phosvitin with 35% phosphate retention detail to highlight the differences between antioxi-

dant and antioxidative stress peptides.

Soy peptides have been found to have increased antioxidant activities compared to intact proteins (Chen et al. 1998 ). The enzymatic digests of the soy storage proteins β - conglycinin and glycinin, had three to fi ve times higher radical - scavenging activities compared to the unhydrolyzed proteins. During hydrolysis the unfolding of the protein structure exposes amino acids previously “ hidden ” within the parent protein. Amino acids such as His, Tyr, Trp, Met, and Lys have known potent antioxidant activity, and the exposure of these amino acid R groups in peptides increases the oxidant quenching potential (Saito et al. 2003 ). Alteration of the enzyme, temperature, and sample preparation conditions during peptide manufacture can affect the types of peptides and their subsequent antioxidant potential.

Soy protein hydrolysates prepared from native and heated soy protein isolates using different enzymes had varying degrees of hydrolysis (1.7 – 20.6%) and antioxidant activity (28 – 65%) (Pe ñ a - Ramos and Xiong 2002 ). It is important to note soy proteins and soy protein isolates contain nonprotein components such as isofl avones, saponins, phytic acid, and dietary fi bers, which possess bioactive antioxidant properties. Therefore unless these nonprotein components are extracted and removed prior to protein use and processing, the antioxidant properties of soy protein/peptide preparations may be due to the biological activities of these compounds. In addition to

Table 2.1. Antioxidative stress food proteins and peptides.

Sources Proteins/Peptides Test Conditions Oxidative Stress Properties References Egg yolk Phosvitin

phosphopeptides

H 2 0 2 stimulation of Caco - 2 cells ↓ IL - 8, ↓ MDA ↑ GSH, ↑ GR ↑ γ - GCS (activity and