Medical Biochemistry PDF
Preview Medical Biochemistry
Medical FIFTH EDITION BIOCHEMISTRY JOHN W. BAYNES, PhD Carolina Distinguished Professor Emeritus Department of Pharmacology, Physiology and Neuroscience University of South Carolina School of Medicine Columbia, SC, USA MAREK H. DOMINICZAK, MD, Dr Hab Med, FRCPath, FRCP (Glas) Hon Professor of Clinical Biochemistry and Medical Humanities College of Medical, Veterinary and Life Sciences University of Glasgow Glasgow, Scotland, UK Docent in Laboratory Medicine University of Turku Turku, Finland Consultant Biochemist Clinical Biochemistry Service National Health Service (NHS) Greater Glasgow and Clyde Gartnavel General Hospital Glasgow, Scotland, UK Caption: Resident2. Pencil on paper by Marek H. Dominiczak© Your medical studies culminate in becoming a resident, where you will be in a position to help patients by solving clinical problems. This will require you to make decisions on diagnosis and treatment. The reason you learn basic science, including biochemistry, is to hone your clinical thinking so that these decisions are better. We have placed this sketch by Marek Dominiczak here to remind ourselves that one should always see learning biochem- istry in the context of this future role. © 2019, Elsevier Limited. All rights reserved. First edition 1999 Second edition 2005 Third edition 2009 Fourth edition 2014 Fifth edition 2019 The right of John W Baynes and Marek H Dominiczak to be identified as author(s) of this work has been asserted by them in accordance with the Copyright, Designs and Patents Act 1988. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds or experiments described herein. Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made. To the fullest extent of the law, no responsibility is assumed by Elsevier, authors, editors or contributors for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. ISBN: 978-0-7020-7299-4 Content Strategist: Jeremy Bowes Content Development Specialist: Nani Clansey Project Manager: Beula Christopher Design: Paula Catalano Illustration Manager: Karen Giacomucci Marketing Manager: Melissa Darling The publisher’s policy is to use paper manufactured from sustainable forests Printed in China Last digit is the print number: 9 8 7 6 5 4 3 2 1 List of Contributors Catherine N. Bagot, BSc, MBBS, MD, Marek H. Dominiczak, MD, Dr Hab Med, MRCP, FRCPath FRCPath, FRCP (Glas) Consultant Haematologist Hon Professor of Clinical Biochemistry and Medical Department of Haematology, Glasgow Royal Infirmary Humanities Glasgow, Scotland, UK College of Medical, Veterinary and Life Sciences University of Glasgow John W. Baynes, PhD Glasgow, Scotland, UK; Carolina Distinguished Professor Emeritus Docent in Laboratory Medicine Department of Pharmacology, Physiology and Neuroscience University of Turku, University of South Carolina School of Medicine Turku, Finland; Columbia, SC, USA Consultant Biochemist Clinical Biochemistry Service Hanna Bielarczyk, PhD National Health Service (NHS) Greater Glasgow and Clyde Assistant Professor and Chair Gartnavel General Hospital Department of Laboratory Medicine Glasgow, Scotland, UK Medical University of Gdańsk Gdańsk, Poland Alan D. Elbein, PhD (deceased) Professor and Chair Iain Broom, DSc, MBChB, FRCPath, Department of Biochemistry and Molecular Biology FRCP (Glas), FRCPE University of Arkansas for Medical Sciences Professor Emeritus of Metabolic Medicine Little Rock, AR, USA Aberdeen Centre for Energy Regulation and Obesity University of Aberdeen Norma Frizzell, PhD Aberdeen, Scotland, UK Associate Professor Department of Pharmacology, Physiology and Neuroscience Wayne E. Carver, PhD University of South Carolina School of Medicine Professor and Chair Columbia, SC, USA Department of Cell Biology and Anatomy University of South Carolina School of Medicine Junichi Fujii, PhD Columbia, SC, USA Professor Department of Biochemistry and Molecular Biology David Church, BMedSci (Hons), MSc, Graduate School of Science, MRCP Yamagata University Clinical Research Fellow Yamagata, Japan Honorary Specialty Registrar University of Cambridge Metabolic Research Laboratories J. Alastair Gracie, PhD BSc (Hons) Wellcome Trust-MRC Institute of Metabolic Science; Senior University Teacher National Institute for Health Research Cambridge School of Medicine, Dentistry and Nursing Biomedical Research Centre; College of Medical, Veterinary and Life Sciences Department of Clinical Biochemistry and Immunology University of Glasgow Addenbrooke’s Hospital Glasgow, Scotland, UK Cambridge, UK ix x List of Contributors Alejandro Gugliucci, MD, PhD Gur P. Kaushal, PhD Professor of Biochemistry and Associate Dean Professor of Medicine Touro University California College of Osteopathic Medicine University of Arkansas for Medical Sciences; Vallejo, CA, USA Research Career Scientist Central Arkansas Veterans Healthcare System Margaret M. Harnett, PhD Little Rock, AR, USA Professor of Immune Signalling Institute of Infection, Immunity and Inflammation Walter Kolch, MD University of Glasgow Professor, Director, Systems Biology Ireland Glasgow, Scotland, UK University College Dublin Belfield, Dublin, Ireland Simon J. R. Heales, PhD, FRCPath Professor of Clinical Chemistry Matthew C. Kostek, PhD, FACSM, HFS Neurometabolic Unit, National Hospital Associate Professor Queen Square and Laboratory Medicine Department of Physical Therapy Great Ormond Street Hospital Duquesne University London, UK Pittsburgh, PA, USA George M. Helmkamp, Jr., PhD Jennifer Logue, MBChB, MRCP, MD, Emeritus Professor of Biochemistry FRCPath Department of Biochemistry and Molecular Biology Clinical Senior Lecturer and Honorary Consultant in University of Kansas School of Medicine Metabolic Medicine Kansas City, KS, USA Institute of Cardiovascular and Medical Sciences University of Glasgow Koichi Honke, MD, PhD Glasgow, Scotland, UK Professor of Biochemistry Department of Biochemistry Masatomo Maeda, PhD Kochi University Medical School Professor of Molecular Biology Kochi, Japan Department of Molecular Biology School of Pharmacy Edel M. Hyland, PhD Iwate Medical University Lecturer in Biochemistry Iwate, Japan School of Biological Sciences Queen’s University Belfast Teresita Menini, MD, MS Belfast, Northern Ireland, UK Professor and Assistant Dean Touro University California College of Osteopathic Medicine Susan Johnston, BSc, MSc, FRCPath Vallejo, CA, USA Clinical Biochemist Clinical Biochemistry Service Alison M. Michie, PhD National Health Service (NHS) Greater Glasgow and Clyde Reader in Molecular Lymphopoiesis Glasgow, Scotland, UK Institute of Cancer Sciences University of Glasgow Alan F. Jones, MA, MB, BChir, DPhil, FRCP, Glasgow, Scotland, UK FRCPath Consultant Physician and Divisional Director Ryoji Nagai, PhD Heart of England NHS Foundation Trust Associate Professor Bordesley Green East Laboratory of Food and Regulation Biology Birmingham, UK School of Agriculture Tokai University Fredrik Karpe, MD, PhD Kumamoto, Japan Professor of Metabolic Medicine Oxford Centre for Diabetes, Endocrinology and Metabolism Radcliffe Department of Medicine University of Oxford Oxford, UK List of Contributors xi Jeffrey R. Patton, PhD Robert Semple, PhD, FRCP Associate Professor Reader in Endocrinology and Metabolism Department of Pathology, Microbiology and Immunology Wellcome Trust Senior Research Fellow in Clinical Science; University of South Carolina School of Medicine Honorary Consultant Physician Columbia, SC, USA University of Cambridge Metabolic Research Laboratories Wellcome Trust-MRC Institute of Metabolic Science; Verica Paunovic, PhD National Institute for Health Research Cambridge Research Associate Biomedical Research Centre Institute of Microbiology and Immunology Cambridge, UK School of Medicine University of Belgrade L. William Stillway, PhD Belgrade, Serbia Emeritus Professor of Biochemistry and Molecular Biology Department of Biochemistry and Molecular Biology Georgia Perona-Wright, PhD, MA, BA Medical University of South Carolina Senior Lecturer Charleston, SC, USA Institute of Infection, Immunity and Inflammation College of Medical, Veterinary and Life Sciences Mirosława Szczepan´ska-Konkel, PhD University of Glasgow Emeritus Professor of Clinical Chemistry Glasgow, Scotland, UK Department of Clinical Chemistry Medical University of Gdańsk Andrew R. Pitt, PhD Gdańsk, Poland Professor of Pharmaceutical Chemistry and Chemical Biology Andrzej Szutowicz, MD, PhD Life and Health Sciences Professor, Department of Laboratory Medicine Aston University Medical University of Gdańsk Birmingham, UK Gdańsk, Poland Simon Pope, PhD Naoyuki Taniguchi, MD, PhD Clinical Biochemist Group Director, Systems Glycobiology Group Neurometabolic Unit RIKEN Advanced Science Institute National Hospital Saitama, Japan UCLH Foundation Trust London, UK Yee Ping Teoh, FRCPATH, MRCP, MBBS Consultant in Chemical Pathology Matthew Priest, MB, ChB, FRCP (Glas) Biochemistry Department Consultant Gastroenterologist and Honorary Senior Wrexham Maelor Hospital Lecturer Wrexham, UK NHS Greater Glasgow and Clyde and University of Glasgow Glasgow, Scotland, UK Robert W. Thornburg, PhD Professor of Biochemistry Allen B. Rawitch, PhD Department of Biochemistry, Biophysics and Molecular Vice Chancellor Emeritus Biology Emeritus Professor of Biochemistry and Molecular Biology Iowa State University University of Kansas Medical Center Ames, IA, USA Kansas City, KS, USA Ian P. Salt, PhD Senior Lecturer Institute of Cardiovascular and Medical Sciences University of Glasgow Glasgow, Scotland, UK Acknowledgments First of all, we wish to thank our contributors for sharing their to provide us with comments, suggestions, and criticisms. We expertise with us and for fitting the writing—again—into their acknowledge the contribution of scholars who participated in busy research, teaching, and clinical schedules. In the 5th the writing of previous editions of Medical Biochemistry: Gary edition, we are delighted to welcome new contributors: David A Bannon, Graham Beastall, Robert Best, James A Carson, Church, Edel Hyland, Susan Johnston, Simon Pope, Teresita Alex Farrell (deceased), William D Fraser, Helen S Goodridge, Menini, and Georgia Perona-Wright. D Margaret Hunt, Andrew Jamieson, W Stephen Kistler, Utkarsh As in the previous edition, we greatly value the excellent V Kulkarni, Edward J Thompson, and A Michael Wallace secretarial assistance of Jacky Gardiner in Glasgow. (deceased). Our inspiration to change and improve this text comes Last but not least, the key to success of the whole project from the problems, questions, and decisions that arise in our has been, of course, the Elsevier team. Our thanks go to Nani everyday clinical practice, in the outpatient clinics, and on the Clansey, Senior Development Editor, whose expertise and hospital wards. We are grateful to all our clinical colleagues and enthusiasm steered the project through; to Madelene Hyde, doctors in training for their insight, discussions, and sharing of who formulated the strategy; to Jeremy Bowes for his contribu- their clinical experience. We are also grateful to students and tion to the initial stages of this edition; and to Beula Christopher, academics from universities around the world who continue who gave the book its final form. xiii To inspirational academics Inquisitive students And all those who want to be good doctors Preface Medical Biochemistry has now served the global medical on the entire field. The details of this reorganization are sum- student community for 19 years. In the 5th edition our aim marized in Chapter 1. remains, as before, to provide a biochemical foundation for We have also updated literature and web references through- the study of clinical medicine—with down-to-earth practical out the textbook. To facilitate familiarity with new terminologies relevance. and acronyms currently abundant in the scientific slang, in Each edition has provided a snapshot of a constantly chang- this edition we have provided an easily accessible list of abbrevia- ing field. Perhaps the most exciting sign of progress is the tions in each chapter. We have also expanded the index to ever-increasing relevance of basic science to the practice of provide more comprehensive access to topics discussed in the medicine, expressed in new drugs targeting biochemical regula- text. tory and metabolic pathways and in new concepts that both We now have even more clinical cases throughout the book, change and supplement our approaches to everyday clinical plus additional cases in Appendix 2. We hope that these will challenges. strengthen the link between biochemistry and clinical medi- Apart from describing the core of basic science, we continue cine and provide a stronger foundation for clinical problem to emphasize the contribution of biochemistry to the under- solving. standing of major global health problems such as diabetes A question bank for self-assessment and many more mellitus, obesity, malnutrition, and atherosclerotic cardiovas- resources are available at the Elsevier website, www.student- cular disease. As before, we remain convinced that the bio- consult.com, to which the reader is referred. There is also a chemistry of water, electrolyte, and acid–base balance is as companion publication, Medical Biochemistry Flash Cards, which important for future clinicians as are the key metabolic provides a means for quick review. pathways and thus deserves more emphasis in the biochemistry As before, we welcome comments, criticisms, and suggestions curriculum. from our readers. There is no better way to continue making In addition to substantial updates, we have changed the this a better text. structure of the book, aiming to provide a clearer perspective xvii Abbreviations 1,25(OH)D 1,25-dihydroxycholecalciferol, calcitriol ALL Acute lymphoblastic leukemia 2 3 1,3-BPG 1,3-bisphosphoglycerate ALP Alkaline phosphatase 17-OHP 17-hydroxyprogesterone ALPS Autoimmune lymphoproliferative 2,3-BPG 2,3-bisphosphoglycerate syndrome 4E-BP1 eIF4E-binding protein 1 ALT Alanine aminotransferase 5-ALA 5-aminolevulinate AML Acute myeloid leukemia 5-HIAA 5-hydroxyindoleacetic acid AMPA α-amino-3-hydroxy-5-methyl-4- 5-HT 5-hydroxytryptamine, serotonin isoxazolepropionic acid 8-oxoG 8-oxo-2′-deoxyguanosine AMPK AMP-activated protein kinase; α-MSH Melanocortin AMP-dependent protein kinase A1AT Alpha-1 antitrypsin ANP Atrial natriuretic peptide AADC Aromatic amino acid decarboxylase AP-1 Activator protein-1 ABC ATP binding cassette APAF1 Apoptotic protease activating factor 1 ABCA1, ABCG5, ATP-binding cassette transporters APC Anaphase-promoting complex G8, A1, G1, and APC Antigen-presenting cell G4 apoA Apolipoprotein A Abl Nonreceptor protein tyrosine kinase apoB Apolipoprotein B ACAT Acyl-CoA: acyl-cholesterol transferase apoB100/apoB48 Apolipoprotein B ACAT Cholesterol acyltransferase apoC Apolipoprotein C ACC1, ACC2 Acetyl-CoA carboxylase ApoE Apolipoprotein E ACD Autophagic cell death (autophagy) APP Amyloid precursor protein ACE Angiotensin-converting enzyme APRT Adenosine phosphoribosyl transferase Acetyl-CoA Acetyl-coenzyme A APTT Activated partial thromboplastin time ACh Acetylcholine AQP Aquaporin ACP Acyl carrier protein ARDS Acute respiratory distress syndrome ACTH Adrenocorticotropic hormone ARE Antioxidant response element AD Alzheimer’s disease ASCVD Atherosclerotic cardiovascular disease ADA American Diabetes Association AST Aspartate aminotransferase ADAR Adenosine deaminase acting on RNA AT1, AT2 Angiotensin receptors ADH Alcohol dehydrogenase ATCase Aspartate transcarbamoylase ADH Antidiuretic hormone, vasopressin ATF Activation transcription factor AE Anion exchanger ATG Autophagy-related gene AFP α-fetoprotein ATM Ataxia-telangiectasia mutated, checkpoint AG Anion gap kinase AGE Advanced glycation (glycoxidation) end ATP III National Cholesterol Education Treatment products Panel III AGPAT2 Acylglycerol acyltransferase 2 ATP Adenosine triphosphate AHA American Heart Association ATR Ataxia-telangiectasia Rad3–related AHF Antihemophilic factor checkpoint kinase, CHK1 and CHK2 AI Adequate Intake AUC Area under the curve AIC Acute intermittent porphyria AVP Arginine vasopressin Akt Protein kinase AZT Azidothymidine ALD Alcoholic liver disease BAD Bcl-2-associated death promoter ALDH Aldehyde dehydrogenase Bak Bcl-2 homologous antagonist/killer ALE Advanced lipoxidation end-products BAX Bcl-2-associated X protein xix
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