Protein Turnover This page intentionally left blank Protein Turnover J.C. Waterlow CABI is a trading name of CAB International CABI Head Office CABI North American Office Nosworthy Way 875 Massachusetts Avenue Wallingford 7th Floor Oxfordshire OX10 8DE Cambridge, MA 02139 UK USA Tel: +44 (0)1491 832111 Tel: +1 617 395 4056 Fax: +44 (0)1491 833508 Fax: +1 617 354 6875 E-mail: cabi@cabi.org E-mail: cabi-nao@cabi.org Web site: www.cabi.org © J.C. Waterlow 2006. All rights reserved. No part of this publication may be reproduced in any form or by any means, electronically, mechanically, by photo- copying, recording or otherwise, without the prior permission of the copyright owners. A catalogue record for this book is available from the British Library, London, UK. A catalogue record for this book is available from the Library of Congress, Washington, DC. ISBN-10: 0-85199-613-2 ISBN-13: 978-0-85199-613-4 Produced and typeset by Columns Design Ltd, Reading Printed and bound in the UK by Biddles Ltd, Kings Lynn, UK Contents Foreword ix Acknowledgements xi 1 Basic Principles 1 1.1 Definitions 1 1.2 Notation 2 1.3 Equivalence of Tracer and Tracee 3 1.4 The Kinetics of Protein Turnover 3 1.5 References 6 2 Models and Their Analysis 7 2.1 Models 7 2.2 Compartmental Analysis 8 2.3 Stochastic Analysis 14 2.4 References 17 3 Free Amino Acids: Their Pools, Kinetics and Transport 20 3.1 Amino Acid Pools 20 3.2 Nutritional Effects on the Free Amino Acid Pools 24 3.3 Kinetics of Free Amino Acids 25 3.4 Amino Acid Transport Across Cell Membranes 27 3.5 Conclusion 29 3.6 References 30 4 Metabolism of Some Amino Acids 33 4.1 Leucine 33 4.2 Glycine 35 4.3 Alanine 38 4.4 Glutamine 40 4.5 Glutamic acid 43 4.6 Phenylalanine 44 4.7 Arginine 45 v 4.8 Methionine 46 4.9 References 47 5 The Precursor Problem 54 5.1 Transfer-RNA as the Precursor for Synthesis 54 5.2 A ‘Reciprocal’ Metabolite as Precursor 55 5.3 A Rapidly Synthesized Protein as Precursor 59 5.4 Conclusion 60 5.5 References 61 6 Precursor Method: Whole Body Protein Turnover Measured by the Precursor Method 64 6.1 Background 64 6.2 Outline of the Method 65 6.3 Variability of Whole Body Synthesis Rates in Healthy Adults by the Precursor Method 65 6.4 Sites of Administration and of Sampling 66 6.5 Priming 68 6.6 The First-pass Effect 69 6.7 Recycling 71 6.8 Regional Turnover 73 6.9 Measurement of Protein Turnover with Amino Acids other than Leucine 76 6.10 Conclusion 79 6.11 References 80 7 Measurement of Whole Body Protein Turnover by the End-product Method 87 7.1 History 87 7.2 Theory 88 7.3 Alternative End-products (EP) 89 7.4 Measurement of Flux with a Single End-product 90 7.5 Behaviour of Different Amino Acids in the End-product Method: Choice of Glycine 92 7.6 Comparisons of Different Protocols 94 7.7 Summary of Measurements of Protein Synthesis in Normal Adults by the End-product Method 94 7.8 Variability 95 7.9 Comparison of Synthesis Rates Measured by the End-product and Precursor Methods 96 7.10 Comparison of Oxidation Rates by the Two Methods 97 7.11 The Flux Ratio 98 7.12 Kinetics Findings by the End-product Method 100 7.13 Conclusion 100 7.14 References 102 8 Amino Acid Oxidation and Urea Metabolism 106 8.1 Amino Acid Oxidation 106 8.2 Metabolism of Urea 109 8.3 References 116 9 The Effects of Food and Hormones on Protein Turnover in the Whole Body and Regions 120 9.1 The Immediate Effects of Food 120 9.2 The Effects of Hormones on Protein Turnover in the Whole Body, Limb or Splanchnic Region 130 9.3 References 135 vi Contents 10 Adaptation to Different Protein Intakes: Protein and Amino Acid Requirements 142 10.1 Adaptation 142 10.2 Requirements for Protein and Amino Acids 148 10.3 References 156 11 Physiological Determinants of Protein Turnover 160 11.1 Body Size – the Contribution of Allometry 160 11.2 Growth and its Cost 165 11.3 The Effect of Muscular Activity and Immobility on Protein Turnover 171 11.4 Conclusion 176 11.5 References 176 12 Whole Body Protein Turnover at Different Ages and in Pregnancy and Lactation 182 12.1 Premature Infants 182 12.2 Neonates 184 12.3 Infants 6 months–2 years 184 12.4 Older Children 186 12.5 Pregnancy 186 12.6 Lactation 190 12.7 The Elderly 191 12.8 References 194 13 Protein Turnover in Some Pathological States: Malnutrition and Trauma 200 13.1 Malnutrition 200 13.2 Trauma 203 13.3 References 207 14 Protein Turnover in Individual Tissues: Methods of Measurement and Relations to RNA 210 14.1 Methods of Breakdown 210 14.2 Measurements of Synthesis 214 14.3 RNA Content and Activity 217 14.4 References 219 15 Protein Turnover in Tissues: Effects of Food and Hormones 223 15.1 Synthesis in the Normal State 223 15.2 The effects of Food on Protein Turnover in Tissues 227 15.3 The Effects of Hormones on Protein Turnover in Tissues 234 15.4 References 241 16 Plasma Proteins 250 16.1 Albumin 250 16.2 Other Nutrient Transport Proteins 258 16.3 The Acute-phase Proteins 259 16.4 The Immunoglobulins 263 16.5 References 264 17 Collagen Turnover 270 17.1 Collagen Turnover 270 17.2 Markers of Synthesis and Breakdown 272 17.3 References 273 Contents vii 18 The Coordination of Synthesis and Breakdown 275 18.1 Synthesis 275 18.2 Breakdown 276 18.3 Coordination 281 18.4 References 283 Index 287 Foreword When I first planned this book my idea was to produce an update of the book we published in 1978 on Protein Turnover in Mammalian Tissues and the Whole Body (Waterlow et al. 1978). It soon became clear that such a vast amount of work has been done in this field in the last 25 years that a new book was needed rather than a revision. But is there a need, since several books have already been produced, such as those of Wolfe (1984, 1992) and Welle (1999), together with numerous reviews and reports of conferences? None of these is entirely comprehensive, giving a conspectus of the whole field. There is, however, another and to me more compelling reason for embarking on this enterprise. Twenty-five years ago, with the increasing availability of stable isotopes and mass spectrometers, a huge new field was opening up for human studies. It extended also to experimental work on animals, since I have been told that it costs less to use stable isotopes than to provide all the facilities needed for working safely with radioisotopes. Good use has been made of these new developments, but I believe we are coming to the end of an era. Even a cursory look at the physiological and clinical journals shows that simple measurement of synthesis and breakdown rates is being overtaken by studies to unravel the molecular biology of these processes. The change of emphasis is part of scientific advance, and is to be welcomed, although many have expressed fears of excessive reductionism; but the pieces, after being taken apart, must be put together again to see how they work as a whole. Here kinetic studies may perhaps play a role. There may be an analogy with the contribution of metabolic control theory to our understanding of the rates of reaction through a sequence of enzymes. An interesting question that has not to my knowledge been tackled is whether the ‘use’ of an enzyme affects its rates of synthesis and breakdown. This is looking forward, in the hope that protein kinetics at the molecular level may still have something to contribute. However, I have another aim in this book: to look back at the past and pay tribute to all who have contributed to our present knowledge, with studies that may be completely forgotten in the future. An example is the work on the turnover of plasma proteins labelled with radioactive iodine isotopes. This dominated two decades, from 1960 to 1980, and produced huge numbers of papers and reports on conferences. One of these, named Protein Turnover (Wolstenholme, 1970) was entirely devoted to plasma proteins, as if no others existed. Has all this work, and the mathematics that went with it, anything to offer us now? I believe that it has, though it would be hard to define exactly what. It is possible that work on whole body protein turnover will meet the same fate as that on iodine- labelled plasma proteins, and disappear into a forgotten limbo. However, I hope that this will not happen, because if it is accepted that protein turnover is a biological process of great importance, ix equivalent to oxygen turnover, then we need to know more about it in different groups of people under different circumstances; we need to bring our knowledge to equal that of oxygen turnover or metabolic rate. In citing references I have used the Harvard system because a name in the text not only refers to a particular paper but recalls a person or a group with whose work I am familiar. Some of these authors I know personally; others I do not, but I feel as if I did. The Harvard system has a human factor which the other systems lack. I apologize to authors whose relevant papers I have missed. Since readers may feel that too many references are cited, to them also I apologize: it is not easy to get the right balance. This book is dedicated to Vernon R. Young, in recognition of his great contribution to the field, his stimulus and comradeship. References Waterlow, J.C., Millward, D.J. and Garlick, P.J. (1978) Protein Turnover in Mammalian Tissues and in the Whole Body. North-Holland, Amsterdam. Welle, S. (1999) Human Protein Metabolism. Springer-Verlag, New York. Wolfe, R.R. (1984) Tracers in Metabolic Research. Radioisotope and Stable Isotope/Mass Spectrometry Methods. Alan Liss, New York. Wolfe, R.R. (1992) Radioactive and Stable Isotopic Tracers in Biomedicine. Wiley-Liss, New York. Wolstenholme, G.E.W. and O’Connor, M. (1970) (eds.) Protein Turnover. CIBA Foundation Symposium no. 9. 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Extraction Lấy ra những nét đặc trưng nhất của ảnh Nhiều công nghệ được sử dụng cho băm ảnh số Đây là bước có nhiều bài báo, nghiên cứu đề xuất các phương pháp để lấy những nét đặc trừng nhất của ảnh Randomization Trong bước này dữ liệu các vector được lấy ra từ bước Freature Extraction sẽ được tạo bản băm bằng việc sử dụng một khóa K Nêu không biết khóa K sẽ không tính được ra giá trị băm của ảnh . 116 9 The Effects of Food and Hormones on Protein Turnover in the Whole Body and Regions 120 9.1 The Immediate Effects of Food 120 9.2 The Effects of Hormones on Protein Turnover in the Whole. Effects of Food and Hormones 223 15.1 Synthesis in the Normal State 223 15.2 The effects of Food on Protein Turnover in Tissues 227 15.3 The Effects of Hormones on Protein Turnover in Tissues 234 15.4. Different Protein Intakes: Protein and Amino Acid Requirements 142 10.1 Adaptation 142 10.2 Requirements for Protein and Amino Acids 148 10.3 References 156 11 Physiological Determinants of Protein Turnover