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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
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
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
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
xix
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xx Abbreviations
DAMPs Damage-associated molecular patterns ERK 1 and 2 Extracellular-signal regulated kinases; two
DAPI 4′-6′-diamidino-2-phenylindole isoforms of MEK kinase that activate
DAT Dopamine transporter MAPK
DC Dendritic cell ESR Erythrocyte sedimentation rate
DCCT Diabetes Control and Complications Trial ETC Electron transport chain
DD Death domain FAD/FADH2 Flavin adenine dinucleotide (oxidized/reduced)
DDI Drug–drug interaction FADD Fas-associated death domain (Fas, death
DED Death effector domain receptor, TNF family member)
DEXA Dual-energy X-ray absorptiometry FasL Fas ligand
DGAT Diacylglycerol acyltransferase Fc “Fragment constant” of immunoglobulin
DHAP Dihydroxyacetone phosphate molecule
DHEA Dehydroepiandrosterone FcγR Fc-γ receptor (receptor for immunoglobulin
DHEAS Dehydroepiandrosterone sulfate G)
DHT Dihydrotestosterone FDB Familial defective apolipoprotein B
DIC Disseminated intravascular coagulation FDPs Fibrin degradation products
DILI Drug-induced liver injury FGF Fibroblast growth factor
DISC Death-inducing signaling complex FGFR3 Fibroblast growth factor receptor 3
DIT Diiodotyrosine FH Familial hypercholesterolemia
DLDH Dihydrolipoyl dehydrogenase FIRKO Adipose tissue (fat) insulin receptor
DLTA Dihydrolipoyl transacetylase knockout
DMP Dentin matrix protein FISH Fluorescence in situ hybridization
DNA Deoxyribonucleic acid FMN Flavin mononucleotide
DNL De novo lipogenesis FOXA2 Transcription factor, also known as
DNP Dinitrophenol HNF-3B
Dol Dolichol FOXO Forkhead box O proteins; transcription
DPP-4 Dipeptidyl peptidase-4 factors belonging to the forkhead family
DPPC Dipalmitoylphosphatidylcholine (contain proteins designated FOXA to
DRI Dietary Reference Intakes FOXR)
dsRNA Double stranded RNA FOXP3 Transcription factor
DTI Direct thrombin inhibitor FP Flavoprotein
DVT Deep vein thrombosis FRTA Free radical theory of aging
E2F Family of transcription factors Fru-1,6-BP Fructose-1,6-bisphosphate
EAR Estimated Average Requirement Fru-1,6-BPase Fructose 1,6-biphosphatase
EBNA1 The Epstein–Barr virus nuclear antigen 1 Fru-1,6-BPase Fructose-1,6-bisphosphatase
ECF Extracellular fluid Fru-1-P Fructose-1-phosphate
ECM Extracellular matrix Fru-2,6-BP Fructose 2,6-biphosphate
EDRF Endothelium-derived relaxing factor (nitric Fru-2,6-BPase Fructose-2,6-bisphosphatase
oxide) Fru-6-P Fructose-6-phosphate
EDTA Ethylenediaminetetraacetic acid FSF Fibrin-stabilizing factor
eEF Eukaryotic elongation factor FSH Follicle-stimulating hormone
EFA Essential fatty acid fT3 and fT4 Free T3 and free T4
EGF Epidermal growth factor FVII Factor VII
EGFR Epidermal growth factor receptor FXR Farnesyl X receptor
eGFR Estimated glomerular filtration rate Fyn Nonreceptor protein tyrosine kinase
eIF Eukaryotic initiation factor G0 Resting, or quiescent, phase
EMSA Electrophoretic mobility shift assay G1 Interval between M and S phases
ENaC Amiloride-sensitive calcium channel G2 Interval between S and M phases
ENaC Epithelial sodium channel G6PDH Glucose-6-phosphate dehydrogenase
eNOS Endothelial nitric oxide synthase GABA γ-Aminobutyric acid
EPA Eicosapentaenoic acid GAD Glutamic acid decarboxylase
Epacs Exchange proteins directly activated by GAG Glycosaminoglycan
cAMP Gal Galactose
ER Endoplasmic reticulum Gal-1-P Galactose-1-phosphate
ERAD ER-associated degradation pathway GALD-3-P Glyceraldehyde-3-phosphate
eRF Eukaryotic releasing factor complex GalNAc N-acetylgalactosamine
xxii Abbreviations
IRI Ischemic reperfusion injury MDRD Modification of diet in renal disease study
IRS Insulin receptor substrate MEK Mitogen-activated protein kinase. A protein
ITAM/ITIM Immunoreceptor tyrosine activation/ kinase that activates MAPK
inhibition motif MET Metabolic equivalent of task
IU International unit metHb Methemoglobin (Fe+3)
JAK Janus kinase MetSO Methionine sulfoxide
JAK/STAT Janus kinase/signal transducer and MGO Methylglyoxal
activator of transcription MHC Major histocompatibility complex
JNK C-Jun terminal kinase miRNA MicroRNA
kb Kilobase MIT Monoiodotyrosine
KCC1 K+ and Cl− cotransporter MMP Matrix metalloproteinase
KCCT Kaolin–cephalin clotting time, APTT MMP Mitochondrial membrane potential
KIP2 57-kDa inhibitor of cyclin–CDK complexes MODY Maturity-onset diabetes of the young
KIT Tyrosine kinase 3 genes MPO Myeloperoxidase
KLF Kruppel-like factor MRI Magnetic resonance imaging
Km Michaelis constant MRM Multiple reaction monitoring
LACI Lipoprotein-associated coagulation mRNA Messenger RNA
inhibitor MRP Multidrug resistance-associated protein
LBBB Left bundle branch block MS Mass spectrometry
LC3 Microtubule-associated protein light MSH Melanocyte stimulating hormone
chain 3 MSLP Maximum lifespan potential
LCAT Lecithin:cholesterol acyltransferase mtDNA Mitochondrial DNA
LC-MS Liquid chromatography/mass spectrometry MTHFR 5,10-methylenetetrahydrofolate reductase
LDH Lactate dehydrogenase mTOR Mechanistic target of rapamycin; a serine/
LDL Low-density lipoprotein(s) threonine protein kinase
LFA-1 Lymphocyte function–associated antigen 1 mTORC-1 and mTor complexes
LH Luteinizing hormone mTORC-2
LMWH Low-molecular-weight heparin mTORC Mammalian target of rapamycin complex
lncRNA Long non-coding RNA MTP Microsomal transfer protein
LPL Lipoprotein lipase MudPIT Multidimensional protein identification
LPLAT Lysophospholipid acyltransferase technology
LPS Lipopolysaccharide MWCO Molecular weight cut-off
LRP5 LDL-receptor-related protein 5 Myc Transcription factor
LSC Laser-scanning cytometry N5MeTHF 5-methyl tetrahydrofolate
LT Leukotriene N5-N10-THF N5-N10-tetrahydrofolate
LTA Light transmission aggregometry NAA N-acetyl-l-aspartate
LXR Liver X receptors NABQI N-acetyl benzoquinoneimine
M Mitosis NAC N-acetylcysteine
MAC-1 Macrophage adhesion molecule 1 NAD+/NADH Nicotinamide adenine dinucleotide
MAG Monoacylglycerol (oxidized/reduced)
MALT Mucosa-associated lymphoid tissues NADP+ Nicotinamide adenine dinucleotide
Man-6-P Mannose-6-phosphate phosphate
MAO Monoamine oxidase NADPH Nicotinamide dinucleotide phosphate
MAOI Monoamine oxidase inhibitor (reduced)
MAPK Mitogen-activated protein kinase NAFLD Nonalcoholic fatty liver disease
MAS Angiotensin 1–7 receptor NCC Sodium–chloride co-transporter
Mb Myoglobin ncRNA Non-coding RNA
MBL Mannose-binding lectin NEFA Nonesterified fatty acid
MCH Melanin-concentrating hormone NeuAc Neuraminic (sialic) acid
MCL Mantle cell lymphoma NFAT2 Transcription factor; nuclear factor of
MCP Multicatalytic protease activated T cells-2
MCP-1 Monocyte chemoattractant protein 1 NFκB Nuclear factor kappa-light-chain-enhancer
M-CSF Monocyte-colony stimulating factor of activated B cell
MCV Mean corpuscular volume NGF Nerve growth factor
MDA Malondialdehyde NGS Next generation sequencing
xxiv Abbreviations