BIOACTIVE PEPTIDES

LINK DOWNLOAD MIỄN PHÍ TÀI LIỆU "BIOACTIVE PEPTIDES": http://123doc.vn/document/568894-bioactive-peptides.htm

CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742
© 2010 by Taylor and Francis Group, LLC
CRC Press is an imprint of Taylor & Francis Group, an Informa business
No claim to original U.S. Government works
Printed in the United States of America on acid-free paper
10 9 8 7 6 5 4 3 2 1
International Standard Book Number-13: 978-1-4398-1363-8 (Ebook-PDF)
This book contains information obtained from authentic and highly regarded sources. Reasonable efforts
have been made to publish reliable data and information, but the author and publisher cannot assume
responsibility for the validity of all materials or the consequences of their use. The authors and publishers
have attempted to trace the copyright holders of all material reproduced in this publication and apologize to
copyright holders if permission to publish in this form has not been obtained. If any copyright material has
not been acknowledged please write and let us know so we may rectify in any future reprint.
Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmit-
ted, or utilized in any form by any electronic, mechanical, or other means, now known or hereafter invented,
including photocopying, microfilming, and recording, or in any information storage or retrieval system,
without written permission from the publishers.
For permission to photocopy or use material electronically from this work, please access www.copyright.
com (http://www.copyright.com/) or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood
Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and
registration for a variety of users. For organizations that have been granted a photocopy license by the CCC,
a separate system of payment has been arranged.
Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used
only for identification and explanation without intent to infringe.
Visit the Taylor & Francis Web site at
http://www.taylorandfrancis.com
and the CRC Press Web site at
http://www.crcpress.com
v
Contents
Preface xv
Acknowledgments xvii
Author xix
1 Chapter Nutrition and the Host Response to Infection and Injury 1
1.1 Nutrition and Illness 1
1.1.1 Introduction 1
1.1.2 Infection and Undernutrition 2
1.1.3 Nutritional Status and Immune Function 2
1.1.4 The Undernutrition-Infection Paradigm 2
1.2 Host Response to Injury 3
1.2.1 The Ebb and Flow Phases 3
1.2.2 Molecular Aspects of the Host Response
to Injury 3
1.2.3 The Infection-In ammatory Response 5
1.2.4 Neuroendocrine Responses to Illness and Stress 5
1.3 Unintended Weight Loss 6
1.3.1 Sickness-Related Weight Loss 6
1.3.2 Illness Anorexia 7
1.3.3 Cachexia 8
1.3.4 Starvation Weight Loss versus Cachexia 10
1.3.5 Fat-Free Mass and Body Composition
during Illness 11
1.3.6 Weight Loss and Mortality Risk 12
1.3.7 Premature or Preterm Infants 12
1.4 Multimodal Nutritional Support Using Bioactive Peptides 13
1.4.1 Nutritional Support 13
1.4.2 Anti-In ammatory Therapy and Wasting 13
1.4.3 Infection and Antisepsis 13
1.4.4 Anabolic Dysfunction 14
1.4.5 Anorexia and Food Intake 14
1.4.6 Antioxidant Capacity 14
1.5 Summary and Conclusions 14
References 16
vi Contents
2 Chapter Bioactive Peptides for Nutrition and Health 21
2.1 Legislation 21
2.1.1 Introduction 21
2.1.2 Dietary Supplements 22
2.1.3 Foods for Special Medical Purposes 23
2.1.4 Medical Foods 24
2.1.5 EU Legislation for Dietetic Foods 26
2.1.6 Functional Foods 27
2.1.7 Protein and Peptide Medical Foods 29
2.2 Bioactive Peptides and Proteins 30
2.2.1 Bioactive Compounds 30
2.2.2 Bioactive Peptide–Related Nutritional
Phenomena 31
2.2.2.1 Bioactive Peptides in Body
Compartments 32
2.2.2.2 Exogenous Bioactive Peptides
Associated with Foods 32
2.2.3 Gene-Encoded Bioactive Peptides 32
2.2.4 Bioactive Peptides and the Cryptome 33
2.2.5 Commercial Bioactive Peptides 34
2.2.6 Nutrigenomics Considerations 34
2.3 Applications of Protein Supplements for Health 35
2.3.1 Heterogeneous versus Enriched Supplements 35
2.3.2 Bone and Hip Fractures 36
2.3.3 Elderly Malnourished Patients 36
2.3.4 Pregnancy 37
2.3.5 Muscle Strength from Resistance Exercise 37
2.3.6 Insulin-Stimulating Activity 37
2.3.7 Protein Supplementation and Cardiovascular
Health 38
2.4 Perspectives on Human Trial Data 39
2.4.1 Statistical Effects 39
2.4.2 Health Claims for Foods and Supplements 40
2.4.3 Safety and Side Effects of Bioactive Peptides
and Proteins 41
2.5 Summary and Conclusions 41
Appendices 42
References 48
Contents vii
3 Chapter Dietary Protein Requirements for Health 59
3.1 Introduction 59
3.1.1 Protein-Energy Undernutrition 59
3.1.2 Detection of Protein-Energy Undernutrition 60
3.1.3 Incidence and Consequences of
Undernutrition 61
3.2 Dietary Protein Quality Relation to Health 62
3.2.1 Protein Quality and Nutritive Properties 62
3.2.2 Growth Assays for Dietary Protein Quality 63
3.2.3 Nitrogen Balance and Protein Quality 64
3.2.4 Dietary Protein Digestibility Relation
to Nitrogen Balance 65
3.2.5 Ileal Digestibility and Net Postprandial Protein
Utilization 66
3.2.6 Dietary and Body Protein Balances
and Transformations 67
3.3 Protein Requirements and Health 68
3.3.1 Adults 68
3.3.2 Protein Requirements for Aging Adults (Elderly) 69
3.3.3 Protein Requirements for Exercise 70
3.3.4 Preterm Infants and Children 70
3.4 Dietary Protein and Host Responses to Illness 71
3.4.1 Urea-Nitrogen Losses during Illness 71
3.4.2 Acute Phase Protein Synthesis 72
3.4.3 Protein EAA Imbalances during Illness 73
3.5 Peptides and Protein Bioactivity 75
3.5.1 Essential Amino Acid and Dietary Protein
Meta-Nutrients 75
3.5.2 Leucine and the Branched Chain Amino Acids 77
3.5.3 Nutrient Signaling and Gene Interactions 78
3.5.4 Receptor Activation by Bioactive Peptides 79
3.5.5 Amino Acid Deprivation and Growth
Retardation 79
3.5.6 Increased EAA Availability and Gene Expression 82
3.5.7 Microarray Pro ling of Dietary Protein–Gene
Interactions 82
3.6 Types of Dietary Protein Health Effects 84
3.6.1 Types of Health Bene ts 84
3.6.2 Health Bene ts and Non-Absorbed Proteins 84
3.7 Summary and Conclusion 85
Appendices 85
References 86
viii Contents
4 Chapter Protein Turnover and Economics within the Body 97
4.1 Protein Turnover and Wasting 97
4.1.1 Introduction 97
4.1.2 Biological Purpose of Protein Turnover 97
4.1.3 Stable Isotope End Product and Precursor Flux 98
4.1.4 Non-Tracer Methods for Estimation of Turnover 100
4.1.5 Protein Turnover Implications for Nutritional
Support 101
4.2 Baseline Whole Body Protein Turnover 102
4.2.1 Adults 102
4.2.2 Gender and Pregnancy 102
4.3 Regional Protein Turnover 103
4.3.1 Splanchnic Bed Protein Kinetics 103
4.3.2 First-Pass Metabolism of Dietary EAA and
Interorgan Effects 104
4.4 Protein Turnover during Illness 105
4.4.1 Preterm Babies and Children 105
4.4.2 Aging Adults and Sarcopenia 106
4.4.3 HIV/AIDS Infection 107
4.4.4 Burns Patients 108
4.4.5 Cancer Cachexia 108
4.4.6 Chronic Renal Failure and Hemodialysis 110
4.4.7 Diabetes 110
4.4.8 Sepsis 112
4.4.9 Tuberculosis 112
4.4.10 Anabolic Dysfunction Affecting Protein
Turnover 113
4.5 Nutrients and Protein Turnover 114
4.5.1 Dietary Protein Intake and Whole Body Protein
Turnover 114
4.5.2 Skeletal Muscle Protein Turnover 116
4.5.2.1 Animal Studies 116
4.5.2.2 Effect of Nutrients on Skeletal Muscle
Protein Turnover—Human Studies 118
4.6 Slow and Fast Proteins 119
4.6.1 Digestion and Absorption Kinetics 119
4.6.2 Effect of Fast Dietary Proteins on Protein
Turnover 120
4.6.3 Intrinsic versus Extrinsic
Contributions to Fast and Slow Proteins 122
4.6.4 Fast versus Slow Proteins for the Elderly and
Young 123
4.6.5 Insulinotropic Action of Fast Proteins 123
4.7 Summary and Conclusions 124
References 124
Contents ix
5Chapter Major Processes for Muscle Gain and Loss 135
5.1 Introduction 135
5.1.1 Muscle Cells 135
5.1.2 Muscle Stem Cell Proliferation 137
5.1.3 Muscle Stem Cell Differentiation 139
5.1.4 Nutrient Effects on Muscle Stem Cell Growth 140
5.2 Myostatin 140
5.2.1 Double Muscling and Myostatin Mutations 140
5.2.2 Myostatin Structure and Activity 141
5.2.3 Mode of Action of Myostatin 141
5.2.4 Myostatin Role in Wasting Diseases 142
5.2.5 Myostatin Inhibition as Therapy for Muscle
Wasting 144
5.3 Muscle Cell Death and Atrophy 144
5.3.1 Types of Cell Death 144
5.3.2 Muscle Apoptosis and Necrosis 144
5.3.3 Skeletal Muscle Wasting via Apoptosis 146
5.3.4 Lysosome-Mediated Autophagy 147
5.4 Proteolysis via Ubiquitin Proteasome 149
5.4.1 Enzyme Systems for Muscle Wasting 149
5.4.2 Structure of the Ubiquitin-Proteasome 149
5.4.3 Ubiquitin Proteasome and Muscle Wasting 151
5.4.4 Cell Cycle Regulation and the Proteasome 151
5.4.5 UPS and the Immune Response 153
5.5 Further Signaling Pathways for Muscle Atrophy 153
5.5.1 Skeletal Muscle Differentiation Program 154
5.5.2 Nuclear Factor Kappa Beta and Muscle Wasting 154
5.5.3 MuRF and Atrogin-1 Gene Expression 154
5.5.4 AKT/Foxo/Atrogin-1 Pathway and Proteolysis 155
5.5.5 Oxidative Stress and Muscle Wasting 158
5.5.6 Angiotensin-Related Muscle Wasting 158
5.6 Mammalian Target of Rapamycin and Hypertrophy 159
5.6.1 mTOR Function as a Nutrient Sensor 160
5.6.2 Two mTOR Complexes and Their Function 160
5.6.3 Regulation of Protein Synthesis by mTOR 162
5.7 Summary and Conclusions 162
Appendices 162
References 164
x Contents
6Chapter In ammation and Innate Immune Response 181
6.1 Types of In ammation 181
6.1.1 Introduction 181
6.1.2 Acute and Chronic In ammation 181
6.1.3 Infection In ammation 184
6.1.4 Obesity-Related In ammation 185
6.1.5 Chronic In ammation, Illness, and Lifestyle
Factors 187
6.2 Proin ammatory Signaling 188
6.2.1 Proin ammatory Cytokines 188
6.2.2 Transcription Factors for In ammatory
Signaling 189
6.2.3 Redox-Sensitive In ammatory Transcription
Factors 193
6.2.4 MAP Kinases, Phosphatases, and In ammation 194
6.2.5 Renin–Angiotensin System and In ammation 195
6.3 Anti-In ammatory Bioactive Peptides and Supplements 197
6.3.1 Adiponectin 197
6.3.2 Angiotensin-Converting Enzyme Inhibitor
Peptides 198
6.3.3 Antimicrobial Peptide Endotoxin Antagonists 199
6.3.4 Cytokine Antibodies 200
6.3.5 Ghrelin and Growth Hormone Secretagogues 200
6.3.6 Glucocorticoid-Inducible Peptides 202
6.3.6.1 Lipocortin or Annexin-1 203
6.3.6.2 Uteroglobin or Clara Cell 10 Protein 204
6.3.6.3 Anti ammins 205
6.3.7 Map Kinase Inhibitors 205
6.3.8 Melanocortin Peptides and KPV 206
6.3.9 Glutamine and Glutamine Dipeptide 209
6.3.10 Food Proteins and Supplements 210
6.4 In Vivo Applications and Controlled Trials 211
6.4.1 Proof for Anti-In ammatory Action 211
6.4.2 In ammatory Bowel Disease, Colitis, and
Mucosal Injury 212
6.4.3 Systemic In ammatory Response and Sepsis 214
6.4.4 Respiratory Distress Syndrome, Lung Injury
and Related 215
6.4.5 Rheumatoid Arthritis 217
6.5 Summary and Conclusions 218
References 219
Contents xi
7 Chapter Infection and Sepsis 239
7.1 Introduction 239
7.1.1 Bacterial Infections, Sepsis, and Weight Loss 239
7.1.2 Host Antimicrobial Peptides for Innate Defense 240
7.1.3 Antibiotics and Muscle Mass 241
7.2 Pathogen Recognition and Intracellular Signaling 242
7.2.1 Toll-Like Receptors 242
7.2.1.1 TLR in Peripheral Tissues and Muscles 243
7.2.1.2 Lipopolysaccharide Signaling via
TLR4 245
7.2.1.3 Peptidoglycan Signaling via TLR2 245
7.2.1.4 Phagocytosis and TLR Function 246
7.2.2 NOD Intracellular Receptors for Pathogens 246
7.2.3 Toll Polymorphism and the Hygiene Hypothesis 246
7.3 Host Antimicrobial Peptides 247
7.3.1 General Properties 247
7.3.2 Defensins and Cathelicidins 248
7.3.2.1 Defensins 248
7.3.2.2 Cathelicidin or hCAP18 249
7.3.3 Dermaseptins and Frog Peptides 250
7.3.4 Bactericidal/Permeability-Increasing Protein 251
7.3.5 Lactoferrin, Lactoferricin, and Talactoferrin 252
7.4 Functions of Antimicrobial Peptides 253
7.4.1 Antibacterial Activity 253
7.4.2 Anticancer Activity of AMPs 253
7.5 In Vivo Applications and Human-Trials of AMPs 255
7.5.1 General Considerations 255
7.5.2 Burns Injury, Wound Healing 256
7.5.3 Cancer Therapy 256
7.5.4 Infant Diarrhea 257
7.5.5 Helicobacter pylori–Related Ulcers 257
7.5.6 Hepatitis C Treatment 258
7.5.7 Oral Mucositis 258
7.5.8 Ventilator-Associated Pneumonia 258
7.5.9 Sepsis and Endotoxemia 259
7.6 Summary and Conclusions 260
Appendices 261
References 265
xii Contents
8 Chapter Anabolic Dysfunction 275
8.1 Introduction 275
8.1.1 Anabolic–Catabolic Imbalance 275
8.1.2 Anabolic Dysfunction Allied to Nutrient
and Hormone Resistance 275
8.1.3 Protein Synthesis and Breakdown during Illness 277
8.2 Insulin and Muscle Protein Metabolism 278
8.2.1 Insulin Signaling 279
8.2.2 Insulin Resistance of Glucose Metabolism 281
8.2.3 Insulin Resistance of Muscle Protein
Metabolism 282
8.2.4 Insulinotropic Bioactive Peptides 283
8.3 Growth Hormone and IGF-1 285
8.3.1 Properties of Growth Hormone and IGF-1 286
8.3.2 Growth Hormone Receptor Signal Transduction 286
8.3.3 Biological Effects of Growth Hormone/IGF-1
Axis 287
8.3.4 Growth Hormone Resistance 287
8.4 Growth Hormone Secretagogues 289
8.4.1 Growth Hormone Release Peptides 289
8.4.2 Hexarelin and Alexamorelin 290
8.4.3 Ghrelin 292
8.5 Leucine, BCAA, and Related Peptides 294
8.5.1 Essential Amino Acids as Anabolic Agents 294
8.5.2 The Branched-Chain Amino Acids 294
8.5.3 Leucine 295
8.5.4 Whey Protein and Peptides 295
8.6 In Vivo Applications and Clinical Trials 296
8.6.1 Short Bowel Syndrome 296
8.6.2 HIV Patients 298
8.6.3 Chronic Renal Failure 300
8.6.4 Critical Illness and Sepsis 300
8.6.5 Cancer Cachexia and Muscle Wasting 301
8.6.6 Liver Disease 302
8.6.7 Adverse Effects and Safety Concerns 303
References 304
Contents xiii
9 Chapter Bioactive Peptides for Alleviating Illness Anorexia 323
9.1 Illness Anorexia 323
9.1.1 Models for the Regulation of Food Intake 323
9.1.2 Bioactive Peptides and Energy Homeostasis 325
9.1.3 Anorectic Bioactive Peptides 325
9.1.4 Serotonin 326
9.1.5 Cytokines and Food Intake 327
9.2 Leptin and Food Intake 327
9.2.1 Characteristics of Leptin Receptor Signaling 327
9.2.2 Leptin Regulation of Food Intake 328
9.2.3 Leptin Resistance during Obesity 329
9.2.4 Leptin Role in Illness Anorexia 330
9.3 Melanocortin Peptides 331
9.3.1 Melanocyte-Stimulating Hormone 331
9.3.2 Melanocortin Networks to Leptin and Serotonin
Signaling 331
9.3.3 Melanocortin Receptors 331
9.3.4 Peptide Agonists and Antagonists for
Melanocortin Receptors 334
9.4 Ghrelin 337
9.4.1 Characteristics of Ghrelin 337
9.4.2 The Ghrelin Receptor 337
9.4.3 Factors Affecting Ghrelin Release 337
9.4.3.1 Ghrelin Circadian and Ultradian
Rhythms 340
9.4.3.2 Food Intake 341
9.4.3.3 Macronutrient Composition 341
9.4.3.4 Hormones and Ghrelin Secretion 341
9.4.3.5 Ghrelin and Obesity 342
9.4.3.6 Fasting Weight Loss 342
9.4.3.7 Aging and Ghrelin Secretion 343
9.4.3.8 Cachexia 344
9.4.4 Exogenous Ghrelin and Food Intake 345
9.4.5 Mode of Ghrelin Orexigenic Action 346
9.5 Other Bioactive Peptides for Moderating Appetite 346
9.5.1 Agouti-Signaling Protein and AgRP 347
9.5.2 Neuropeptide Y 348
9.5.3 Serotonin Antagonists 348
9.5.4 Dietary Proteins and Satiety 349
9.6 In Vivo Studies and Controlled Trials 351
9.6.1 Cancer Anorexia 351
9.6.2 Pulmonary Obstructive Disease 352
9.6.3 Chronic Kidney Failure and Dialysis Patients 352
9.6.4 HIV Infection Anorexia 353