Ebook Medical biochemistry at a glance (3rd edition) Part 1

Dedication
In memory of Gordon Hartman (1936–2004), friend and colleague whose enthusiasm and
encyclopaedic knowledge were an asset to all who knew him.


glycogen

glycogen
(n–1 residues)

O2

GLK\GURELRSWHULQ
UHGXFWDVH

PRQRR[\JHQDVH

Pi

L-DOPA

tyrosine

ADP

D-3-hydroxybutyryl ACP

acetyl CoA
cysteine–SH

group of
condensing
enzyme

DOGRODVH

H2O

Cytosol

6DGHQRV\OPHWK\OWUDQVIHUDVH

WULRVHSKRVSKDWH
LVRPHUDVH

Glycolysis

S-adenosylhomocysteine

glutamate

glyceraldehyde
3-phosphate
NAD+

Pi

SKRVSKRJO\FHUDWH
NLQDVH
ATP

serine
cysteine

4-hydroxyphenylpyruvate
O2

homogentisate
O2

pyruvate

DPLQRWUDQVIHUDVH

aspartate

4-maleylacetoacetate

CoASH

malonyl ACP
CoASH

many intermediates

PDORQ\O&R$$&3
WUDQVDF\ODVH

HQRODVH

fumarylacetoacetate

S\UXYDWH
NLQDVH
NADPH+H+

GDP CO2
NAD+ NADH+H+
ATP

NAD+

lactate

malate

fumarate
acetoacetate

NADP+

PDOLF
HQ]\PH

ATP

S\UXYDWHFDUER[\ODVH

ATP

ADP+Pi

ADP+Pi

FLWUDWHO\DVH

H2O

CoASH

palmitoyl Co A

FDUQLWLQHDF\OWUDQVIHUDVH,

citrate

S\UXYDWHGHK\GURJHQDVH

4H+

histidine
KLVWLGDVH

urocanate
K\GUDWDVH

folate
cycle

FADH2

NADH+H+

2H+

4-imidazolone5-propionate

4H+

+22

NH4

FIGLU

+

Complex
,9

C
Complex
,,,

2H+
H2O

1
–O
2
2

NADH+H+

Mitochondrion

ATP

NAD

+
NADPH+H

NADP

+

ADP+Pi

glutamate
g-semialdehyde

DPLQRWUDQVIHUDVH

VSRQWDQHRXV

FADH2

NADPH+H

GTP

ADP

GDP Pi

NAD+

H+

QXFOHRVLGHGLSKRVSKDWHNLQDVH

4H+

ATP

Q

ornithine

FADH2
NADH
+H+

NAD+

–12 O2 ADP

+

acetoacetyl CoA
CoASH

WKLRODVH

2H+

4H+

H2O

Pi

myristoyl CoA
(C14)



F1
4H+

Complex
,

WUDQVORFDVH

NADH+H+

Ketogenesis

NADH+H+
glutamate

C4

3-hydroxybutyrate

NH4+

CoASH

FADH2
NADH+H+

“Ketone
bodies"

CO2

a-ketoglutarate

NADH+H+

Pi H+

isocitrate

acetoacetate

H+

ATP

FO
Complex
,,,
4H+

C

Complex
,9
2H+

10H+

Pi

H+
4H+

Respiratory chain
ATP

+

NADP

proline

GDP

acetyl CoA

NADH+H+

aNHWRJOXWDUDWH
GHK\GURJHQDVH

NADH+H+

+

UHGXFWDVH

FAD

Intermembrane
space
Outer membrane

(P 5-C)
SUROLQHR[\JHQDVH

succinyl CoA

FADH2

C6

NAD+

NAD+

GTP

Inner membrane

3&V\QWKHWDVH

+

LVRFLWUDWHGHK\GURJHQDVH

CoASH

glutamate
JOXWDPDWH
gVHPLDOGHK\GH
GHK\GURJHQDVH

VXFFLQ\O&R$
V\QWKHWDVH

succinate

NADH+H+

C8

hydroxymethyl
glutaryl CoA
(HMGCoA)

H2O
DFRQLWDVH

VXFFLQDWH
GHK\GURJHQDVH
FAD

FADH2

CoASH

[cis-aconitate]

Krebs cycle
CO2

N 5-formimino -THF

+
NADH+H

H2O

fumarate

Complex
,,

THF

JOXWDPDWH
IRUPLPLQRWUDQVIHUDVH

acetyl CoA

C10

H2O

DFRQLWDVH

IXPDUDVH

H2O

4H+

citrate

FLWUDWH
V\QWKDVH
H2O
CoASH

FADH2

Q

10

N ,N
-methenyl-THF

ADP

oxaloacetate

b-Oxidation

FADH2
NADH+H+

acetoacetyl CoA

PDODWH
GHK\GURJHQDVH

malate

C12

(8) acetyl CoA

acetyl CoA

NAD+

Pi

6H+

+ 2


3H+

H+

Pi

1+

LPLGD]RORQH
SURSLRQDVH
5

F1

FO
H+

CoASH

C14

NADH+H+

CO2

palmitoylcarnitine

WULFDUER[\ODWH
FDUULHU

–

HCO3

S\URSKRVSKDWDVH

2 Pi

ATP

NAD+

NAD+

CoASH

CoASH

oxaloacetate

S\UXYDWH
FDUULHU

GLFDUER[\ODWH
FDUULHU

ATP

malate

NADH+H+

CO2

oxidised by
extrahepatic
tissues

acetyl CoA

acetoacetyl CoA
PDODWH
GHK\GURJHQDVH

pyruvate

ODFWDWH
GHK\GURJHQDVH

DFHW\O&R$FDUER[\ODVH

HCO3–+ATP

ADP
GTP

PDODWH
GHK\GURJHQDVH

malonyl CoA

NADPH+H+ +
H +ADP+Pi

hydroxymethyl
glutaryl CoA
(HMGCoA)

H2O

malonyl CoA

acyl carrier protein

+0*&R$
UHGXFWDVH

phosphoenolpyruvate

NADH+H+

IXPDU\ODFHWRDFHWDVH

NADP+

2-phosphoglycerate

SKRVSKRHQROS\UXYDWH
FDUER[\NLQDVH
oxaloacetate

DPLQRWUDQVIHUDVH

LVRPHUDVH

H2O

CoASH

SKRVSKRJO\FHUDWH
PXWDVH

a-ketoglutarate glutamate

GLR[\JHQDVH

C6
bNHWRDF\O$&3
V\QWKDVH
CO2 FRQGHQVLQJHQ]\PH


mevalonate

alanine

CO2

HQR\O$&3
UHGXFWDVH

NADP+

cholesterol

3-phosphoglycerate

a-ketoglutarate glutamate

GLR[\JHQDVH

NADPH+H+

bNHWRDF\O$&3
V\QWKDVH
CO2 FRQGHQVLQJHQ]\PH


ADP

glycine

enoyl ACP

DFHW\O&R$

WUDQVDF\ODVH

acetoacetyl ACP
C4

1,3-bisphosphoglycerate

adrenaline

bK\GUR[\DF\O$&
3GHK\GUDWDVH

H2O

acyl ACP

JO\FHUDOGHK\GHSKRVSKDWH
GHK\GURJHQDVH

NADH+H+

bNHWRDF\O$&3
UHGXFWDVH

NADP+

ADP

H2O

dihydroxyacetone
phosphate

NADPH+H+

SKRVSKRIUXFWRNLQDVH

fructose
1,6-bisphosphate

S-adenosylmethionine

WUDQVNHWRODVH

glyceraldehyde
3-phosphate

acetoacetyl ACP

glyceraldehyde
3-phosphate

ATP

IUXFWRVH
ELVSKRVSKDWDVH

O2

W\URVLQH

DPLQRWUDQVIHUDVH

WKLDPLQH33


WUDQVDOGRODVH

SKRVSKRJOXFRVH
LVRPHUDVH

dopamine

a-ketoglutarate

SKRVSKRJOXFRQDWH
GHK\GURJHQDVH

fructose
6-phosphate

Endoplasmic reticulum

noradrenaline

CO2

sedoheptulose
7-phosphate

fructose

6-phosphate

Pi

H2O
CO2

NADPH+H+

SKRVSKRJOXFRPXWDVH

JOXFRVH
SKRVSKDWDVH

Pi

ODFWRQDVH

erythrose
4-phosphate

glucose
6-phosphate

JOXFRNLQDVH
KH[RNLQDVH

6-phosphogluconate

Pentose phosphate pathway

(hexose monophosphate shunt)

WUDQVNHWRODVH
0J
WKLDPLQH33


glucose
1-phosphate

NADPH+H+

dihydrobiopterin

H2O

ATP

NADP+

tetrahydrobiopterin

NADP+

H2O

6-phosphogluconod-lactone

fructose
6-phosphate

UTP

GHEUDQFKLQJHQ]\PH
L
JO\FRV\OWUDQVIHUDVH
LL
aÆ
JOXFRVLGDVH

glucose

PPi

8'3JOXFRVHS\URSKRVSKRU\ODVH

JO\FRJHQ
SKRVSKRU\ODVH

NADPH+H+

JOXFRVH
SKRVSKDWH
GHK\GURJHQDVH

uridine diphosphate
glucose

S\URSKRVSKDWDVH

2 Pi

Pi

NADP+

glucose
6-phosphate

a (1Æ4) glucose
oligosaccharide primer
(n residues)

Regulatory enzyme

phenylalanine

JO\FRJHQV\QWKDVH

a (1Æ4) glucose
oligosaccharide
(n +1 residues)

UDP

EUDQFKLQJ
HQ]\PH


tryptophan

ribulose
5-phosphate

ribulose
phosphate
3-epimerase

NADPH+H+

N-formylkynurenine

ribose
5-phosphate
isomerase

xanthurenate
(yellow)

NAD+ and
NADP+
synthesis

carbamoyl aspartate

glycinamide
ribonucleotide (GAR)

ADP+Pi

H2 O

dihydroorotate

N 10-formyl THF

N 10-formyl THF

FMN
FMNH2

THF
H2O

2-aminomuconate
semialdehyde

formylglycinamide
ribonucleotide (FGAR)
H2O
glutamine

N 5, N 10-methenyl THF
NADPH+H+

N , N --methylene THF

NH4+

PPi

glutamate

NADPH+H+

a-ketoadipate

orotate

ATP

NADP+
5
10

2-aminomuconate

Fatty acid synthesis

carbamoyl phosphate
aspartate

ADP+Pi

ATP

Folate
cycle

ADP+Pi

OMP
(orotidine monophosphate)

formylglycinamidine
ribonucleotide (FGAM)

NADP+

N 5-methyl

ATP

THF

CO2

ADP+Pi

UMP
(uridine monophosphate)

AIR
CO2

N5-methyl THF

CAIR

THF
vitamin B12

palmitoyl ACP

C8

C10

CO2
CoASH

C12

CO2
CoASH

C14

CO2

CO2
CoASH

CoASH

thioesterase

homocysteine
acyl
carrier
protein

CO2
CoASH

–CH 3
yl
meth

palmitate
glycerol
3-phosphate

SAM

esterification

ADP

(triacylglycerol)

ATP

3 H2O

hormone
lypolysis (adipose
sensitive lipase
tissue)

PPi+AMP

dCMP
THF

N 5, N 10-methenyl THF

threonine

DHF

IMP
dTMP

GDP

lysine

vitamin B6

glycine

CTP UTP

2 aminoadipate
semialdehyde

homoserine

2-aminoadipate

ATP

dTDP

GTP ATP dGTP dATP dTTP dCTP

RNA

isoleucine

aminotransferase

a-ketobutyrate

long chain acyl CoA synthetase

ADP

saccharopine

cystathionine

(3) palmitate

valine

aminotransferase

a-ketoadipate

a-keto-b-methylvalerate

leucine

aminotransferase

a-ketoisovalerate

DNA

aminotransferase

a-ketoisocaproate

outer CPT

carnitine
carnitine
shuttle

inner CPT
NAD+

CoASH

palmitoyl CoA (C16)

NAD+

CoASH

NADH+H+

CO2

NADH+H+

CO2

glutaryl CoA

propionyl CoA

acyl CoA
dehydrogenase

CoASH

dehydrogenase

dehydrogenase

FAD

carnitine
shuttle
NAD+

CoASH

dehydrogenase
CO2

CoASH

dehydrogenase

NADH+H+ CO2

a-methylbutyryl CoA

carnitine
shuttle
NAD+

NADH+H+

NAD+
dehydrogenase

CO2

NADH+H+

isovaleryl CoA

isobutyryl CoA

THF

FADH2

trans-D2-enoyl CoA
CO2

H2O

5

enoyl CoA
hydratase

L-3-hydroxyacyl CoA

HCO3–

NADH+H+

NH4

CoASH

+

ornithine
transcarbamoylase
2ATP

methylmalonate
semialdehyde

propionyl CoA

citrulline

Odd numbered
fatty acids

Pi

L-3-hydroxyacyl CoA
dehydrogenase

thiolase

CoASH

acetyl CoA

N ,N
-methylene THF

NAD+

3-ketoacyl CoA

acetyl CoA

10

2ADP+Pi

carbamoyl
phosphate

Urea
cycle

acetyl CoA

D-methylmalonyl CoA

acetyl
CoA

L-methylmalonyl CoA

acetoacetate

carbamoyl
phosphate
synthetase I

mutase

acetyl CoA

dUMP

H2O

UTP

cysteine
CoASH

dCDP

AICAR

N 10-formyl
THF

methyl group
transferred to
acceptor

homocysteine

glycerol

CDP

fumarate

S-adenosylhomocysteine

tripalmitin

glycerol kinase
(not in white

adipose tissue)

pyrophosphatase

SAM

methyl
transferase

UTP

SAICAR

FAICAR
(S-adenosylmethionine)

UDP

ATP
ADP+Pi

Methionine
salvage
pathway

H2O

C16

aspartate

UTP

methionine

homocysteine
methyltransferase

carbamoyl
phosphate
synthetase II

2ADP+Pi
glutamate

b-5-phosphoribosylamine
glycine
ATP

THF

2-amino-3-carboxymuconate
semialdehyde

transketolase

glutamate

2ATP

glutamine-PRPP
amidotransferase

(tetrahydrofolate)

alanine
3-hydroxyanthranilate

(thiamine PP)

PRPP

H2 O

NADP+

3-hydroxykynurenine

ribose
5-phosphate

AMP

glutamine

NADPH+H+

kynurenine

xylulose

5-phosphate

ATP

DHF
(dihydrofolate)

formate

bicarbonate
glutamine

ribose 5-phosphate

folate

NADP+

aspartate

ATP

synthetase
AMP+PPi

argininosuccinate
lyase
fumarate

arginine

arginase

ornithine

urea

Vitamin B12

succinyl
CoA



Medical Biochemistry at a Glance


Companion website
This book is accompanied by a companion website which contains interactive Multiple-Choice Questions:
www.ataglanceseries.com/medicalbiochemistry


Medical Biochemistry
at a Glance
Dr J. G. Salway
School of Biomedical and Molecular Sciences
University of Surrey
Guildford
Surrey, UK

Third edition

A John Wiley & Sons, Ltd., Publication


This edition first published 2012 © 2012 by John Wiley & Sons, Ltd.
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of the publisher.
First edition published 1996
Second edition published 2006
Second edition translations:
Chinese Translation 2007 Taiwan Yi Hsien Publishing Co. Ltd
Japanese Translation 2007 Medical Sciences International Ltd, Tokyo
Korean Translation 2007 E*PUBLIC KOREA Co. Ltd
Polish Translation 2009 Górnicki Wydawnictwo Medyczne

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Library of Congress Cataloging-in-Publication Data
Salway, J. G.
  Medical biochemistry at a glance. – 3rd ed. / J.G. Salway.
    p. ; cm. – (At a glance)
  Includes bibliographical references and index.
  ISBN-13: 978-0-470-65451-4 (pbk. : alk. paper)

  ISBN-10: 0-470-65451-1 (pbk. : alk. paper)  1.  Biochemistry–Outlines, syllabi, etc.  2.  Clinical
biochemistry–Outlines, syllabi, etc.  I.  Title.  II.  Series: At a glance series (Oxford, England)
  [DNLM: 1.  Biochemical Phenomena.  QU 34]
  QP514.2.G76 2012
  612'.015–dc23

2011024248
A catalogue record for this book is available from the British Library.
Set in 9 on 11.5 pt Times by Toppan Best-set Premedia Limited
1  2012


Contents
Preface to the third edition  7
Acknowledgements to the third edition  7
Figure key  8
SI/mass unit conversions  9
Part 1  Acids, bases and pH
  1 Acids, bases and hydrogen ions (protons)  10
  2 Understanding pH  12
  3 Production and removal of protons into and from
the blood  14
  4 Metabolic alkalosis and metabolic acidosis  16
  5 Respiratory alkalosis and respiratory acidosis  18
Part 2  Structure of amino acids and proteins
  6 Amino acids and the primary structure of proteins  20
  7 Secondary structure of proteins  22
  8 Tertiary and quaternary structure and collagen  24
Part 3  Formation of ATP: oxidation and reduction
reactions

  9 Oxidation/reduction reactions, coenzymes and prosthetic
groups  26
10 Anaerobic production of ATP by substrate-level phosphorylation,
from phosphocreatine and by the adenylate kinase
(myokinase) reaction  28
11 Aerobic production of ATP  30
12 Biosynthesis of ATP by oxidative phosphorylation I  32
13 Biosynthesis of ATP by oxidative phosphorylation II  34
14 What happens when protons or electrons leak from the
respiratory chain?  36
15 Free radicals, reactive oxygen species and oxidative damage  38
16 Aerobic oxidation of glucose to provide energy as ATP  40
17 Anaerobic oxidation of glucose by glycolysis to form ATP and
lactate  42
18 Anaerobic glycolysis in red blood cells, 2,3-BPG (2,3-DPG) and
the Bohr effect  44
Part 4  Carbohydrates
19 Carbohydrates  46
20 Absorption of carbohydrates and metabolism of galactose  48
21 Fate of glucose in liver: glycogenesis and lipogenesis  50
22 Fructose metabolism  52
23 Glucose homeostasis  54
24 Glucose-stimulated secretion of insulin from β-cells  56
25 Regulation of glycogen metabolism  58
26 Glycogen breakdown (glycogenolysis) and glycogen storage
diseases  60
27 Insulin signal transduction and diabetes mellitus  62
28 Diabetes mellitus  64
29 Alcohol metabolism: hypoglycaemia, hyperlactataemia and
steatosis  66

Part 5  Enzymes and regulation of pathways
30 Enzymes: nomenclature, kinetics and inhibitors  68
31 Regulation of enzyme activity  70

32 Regulation of glycolysis and Krebs cycle  72
33 Oxidation of fatty acids to produce ATP in muscle and ketone
bodies in liver  74
34 Regulation of lipolysis, β-oxidation, ketogenesis and
gluconeogenesis  76
Part 6  Lipids and lipid metabolism
35 Structure of lipids  78
36 Phospholipids I: phospholipids and sphingolipids  80
37 Phospholipids II: micelles, liposomes, lipoproteins and
membranes  82
38 Metabolism of carbohydrate to cholesterol  84
39 VLDL and LDL metabolism I: “forward” cholesterol
transport  86
40 VLDL and LDL metabolism II: endogenous triacylglycerol
transport  88
41 HDL metabolism: “reverse” cholesterol transport  90
42 Absorption and disposal of dietary triacylglycerols and
cholesterol by chylomicrons  92
43 Steroid hormones: aldosterone, cortisol, androgens and
oestrogens  94
Part 7  Metabolism of amino acids and porphyrins
44 Urea cycle and overview of amino acid catabolism  96
45 Non-essential and essential amino acids  98
46 Amino acid metabolism: to energy as ATP; to glucose and
ketone bodies  100
47 Amino acid disorders: maple syrup urine disease,

homocystinuria, cystinuria, alkaptonuria and albinism  102
48 Phenylalanine and tyrosine metabolism in health and
disease  104
49 Products of tryptophan and histidine metabolism  106
50 Haem, bilirubin and porphyria  108
Part 8  Vitamins
51 Fat-soluble vitamins I: vitamins A and D  110
52 Fat-soluble vitamins II: vitamins E and K  112
53 Water-soluble vitamins I: thiamin, riboflavin, niacin and
pantothenate  114
54 Water-soluble vitamins II: pyridoxal phosphate (B6)  116
55 Water-soluble vitamins III: folate and vitamin B12  118
56 Water-soluble vitamins IV: biotin and vitamin C  120
Part 9  Molecular biology
57 The cell cycle  122
58 Pyrimidine metabolism  124
59 Purine metabolism  126
60 Structure of DNA  128
61 The “central dogma” of molecular biology  130
62 Organisation of DNA in chromosomes  132
63 Replication of DNA (part 1)  134
64 Replication of DNA (part 2)  136
65 DNA damage and repair  138
66 Transcription of DNA to make messenger RNA (part 1)  140
67 Transcription of DNA to make messenger RNA (part 2)  142
Contents  5


68 Transcription of DNA to make transfer RNA  144
69 Transcription of DNA to make ribosomal RNA  146

70 Translation and protein synthesis  148
71 Comparison of DNA replication, DNA transcription and protein
synthesis in eukaryotes and prokaryotes  150

Part 10  Diagnostic clinical biochemistry
72 Diagnostic clinical biochemistry (with Dr J. W. Wright FRCP,
MRCPath)  152
Index  154

Companion website
This book is accompanied by a companion website which contains interactive Multiple-Choice Questions:
www.ataglanceseries.com/medicalbiochemistry

6  Contents


Preface to the third edition
The subject matter in Medical Biochemistry at a Glance is selected
from the biochemistry content of First Aid for the USMLE Step 1: the
most popular guide used by students preparing for examinations. As
such, it is written for medical students, but is equally accessible to
students of the biomedical sciences such as biochemists, medical laboratory scientists, veterinary scientists, dentists, pharmacologists, physiologists, physiotherapists, nutritionists, food scientists, nurses,
medical physicists, microbiologists and students of sports science.
This book aspires to present medical biochemistry in the concise twopage format of the “At a Glance” series.
Students who study biochemistry as a subsidiary part of their course
are frequently overwhelmed by the complexity and huge amount of
detail involved. Lecturers will be familiar with the anxious expression
of students as they complain “How much of this do we need to know?”
or “Do we need to memorise all the structural formulae and the chemical reactions?” In fairness, biochemistry is a complex and heavily
detailed subject. Students should have two objectives: (i) to study and

understand biochemical concepts and reactions but not necessarily
memorise the structural details, (ii) to prepare for examinations by

determining the amount of detail required by intelligent perusal of
lecture notes and past examination papers.
Medical Biochemistry at a Glance is written with these two objectives in mind. Judicious study of the back inside cover featuring a
metabolic chart including formulae and the enzymes catalysing the
reactions plus the comprehensive chart on the front inside cover will
enable an understanding of metabolic biochemistry. The enzymes
which regulate metabolic pathways are indicated in both charts and
throughout the book. In the text of the book, complex detail is subjugated to a faint background so as to emphasise the most important
aspects of the topic. However, students must familiarise themselves
with the requirements of their particular examination board to determine how much should be trusted to memory.
Finally, the inspiration for Medical Biochemistry at a Glance has
developed from my book Metabolism at a Glance. The latter is a more
advanced book but the similarity of style between these two books
facilitates progression to a higher level by students specialising in
metabolism and disorders of metabolism.

Acknowledgements to the third edition
Following discussion with my editor, it was clear this new, third
edition must include a section on “Molecular Biology”: not my strongest subject. So the start of this book was marked by a four-day trip to
Cheshire visiting my friends Dr Peter Barth and his wife Jane. Peter
has dedicated his career to molecular biology and so I was most fortunate when he offered to update me in this fascinating subject. Jane
provided excellent food and warm hospitality in their beautiful house.
Peter’s patient, clear and authoritative tuition defined the structure of
the chapters. We also made time for recreation, and together they gave
me a most enjoyable, productive and unforgettable visit. Peter’s
support, advice and encouragement continued through to the last
moments of the final proofs. This book would not have been possible

without Peter’s invaluable help.
Once again I have been very fortunate to work with Elaine
Leggett of Oxford Designers & Illustrators and the facilities
provided by Mr Richard Corfield and his team. Elaine’s first task was
to update the artwork colour scheme from the second edition to full
colour. Then, with her customary aplomb and talent she rose to the
challenge of interpreting my sketches for the new Molecular Biology
section.
At a Christmas drinks party, I met my old colleague Professor Peter
Goldfarb. Inspired with Yuletide spirit, he offered help and generously
gave his time, wise advice with characteristic attention to detail and
constructive criticism.
I am very grateful to readers who have emailed to report errors and
to friends and colleagues for expert advice, especially Dr Kimberly
Dawdy, Dr Lucy Elphick, Dr Anna Gloyn, Professor Keith Frayn, Mrs

Rosemary James, Professor Gary John, Professor George Kass, Dr
Lisa Meira, and Dr Helen Stokes.
Also, I wish again to record my gratitude to those who contributed
to the second edition of this book, namely: Professor Loranne Agius,
Dr Wynne Aherne, Dr Beatrice Evans, Dr Martyn Egerton, Professor
George Elder, Dr Janet Brown, Dr Geoffrey Gibbons, Dr Barry Gould,
Dr Bruce Griffin, Professor Stephen Halloran, Professor Chris
O’Callaghan, Dr Anna Saada, and Mrs Marie Skerry.
Many reviewers commented on the excellent index compiled by
Philip Aslett for the second edition, so I was very pleased when he
agreed to help once more.
My editor Martin Davies has been exceptionally supportive. He has
replied to my emails with extraordinary promptness and provided
every facility requested to ensure efficient completion of the work. Also,

it has been a great pleasure to work with other members of a most professional Wiley-Blackwell team, especially Heather Addison, Lesley
Aslett, Helen Harvey, Karen Moore, Laura Murphy, and Beth Norton.
Regrettably, omissions and errors will have occurred and I would
be most grateful to have these drawn to my attention.
Finally, I am grateful to my wife Nicky once again for her support,
and for tolerating the intrusion of publication deadlines into our social
programme; also the accumulation of documents and papers associated with writing this book.
J. G. Salway
Surrey, UK

Preface and acknowledgements

7


Figure key
Explanation of the cartoon icons
-S-S-

Pathway operates
in cardiac muscle

Therapeutic drug

α

-S-S-

α

-S-S-

active
insulin
receptor

β

P

Disease or poison

Insulin receptor is
activated by
autophosphorylation of the
β-subunits when insulin
binds to the α-subunits

β

P

P

P

P

P

Pathway operates
in skeletal muscle

IRS-1 (insulin receptor
substrate-1)

IRS-1

Associated with diagnostic
blood test

Pathway operates
in liver

Excretion in urine or faeces.
Product may be used in
diagnosis

SAM
–CH 3
yl
meth

p85

P

P85. 85 kDa protein is
regulatory subunit of
PI-3 kinase. Links IRS-1

to PI-3 kinase
PI-3 kinase.
Phosphorylates the
3-hydroxyl group of PIP2 to
form phosphatidylinositol
3,4,5-trisphosphate

Pathway operates
in kidney

SAM
(s-adenosylmethionine)
The methyl-donor man

AKT

Currently the subject of
research, debate or
clinical trials

AKT (previously known as
PKB). A serine/threonine
protein kinase. Binds to
PIP3

P

A hydrophobic group
PDK-1

PDK-1. Phosphoinositidedependent kinase-1 is
activated by
phosphatidylinositol
3,4,5-trisphosphate

Regulatory enzyme
A hydrophilic group
P

Glycogen synthase
kinase -3. Constitutively
active in fasting state.
Is inhibited when
phosphorylated by AKT

GSK-3

Fed state or
dietary intake

cyclic AMP
cyclic AMP
R

R

R
C

C

R

inactive protein
kinase A

Fasting state,
starvation

8  Figure key

active protein
kinase A

PKA (protein kinase A) is activated by cyclic AMP which
binds to and removes the regulatory (inhibiting) subunits

P
1

2

Protein phosphatase-1.
Activated by
insulin-generated signals


SI/mass unit conversions
Total bilirubin

Calcium

Creatinine

(pH 7.35–7.45)

Glucose

[H+]

nmol/l
(35–45 nmol/l)

+

(¥ 17.1)

< 20
µmol/l

< 1.2
mg/dl

(∏ 17.1)

2.0–2.5
mmol/l
4.0

160
9

140

120

(¥ 0.25)

8–10
mg/dl

(∏ 0.25)

16

60–120
µmol/l
800

80

8

14

700

13
3.0

7
6

2.5

12

600

10

500

9

5

2.0

< 6.0
mmol/l

(∏ 0.056)

8

1.5
3
1.0

0.5

500

7
25

450

6

400
20

15

300
3

4

200

3

1

550

30

4

5

2

8

2

100

10
2
5

1

1
0

0

0

Phosphate
Phosphorus
0.6–1.25
mmol/l

(¥ 0.323)

(∏ 0.323)

10
3.0

2.5

9

1.9–3.9
mg/dl

7–25
ρmol/l
80

70

1.5

60

5
4

1.0

50

40

30

20

0

0

6.0
5.5

4.0

3.5

(¥ 0.0113)
(∏ 0.0113)

target
< 133
mg/dl

350

300

3–7
mmol/l

4.5
4.0

3.0
2.5

10

1.5
1.0

0

7.6

25
30

7.5

40

300

7.3

50

250

7.2

200

7.1

150

7.0

70
80
90
100

100

6.9

130

50

6.8

160

0

6.7

200

BUN

(¥ 0.357)
(∏ 0.357)

8–20
mg/dl

60

Total cholesterol
target
< 4.0
mmol/l

(¥ 0.0259)
(∏ 0.0259)

14

40

7

35

5

4

0

150

20
6

3
15

0.5

200

25

150

1.0

300

6

30

8

100

target
< 155
mg/dl

250

4

10

100
2

50

2

5

1

0

0

0

0

0.5
0

20

8

200

1.5

7.7

7.4

10

2.0

15

7.8

45

250
2.5

10

7.9

16

12

3.0

mol/l
e.g. antilog10 of –7.4 = 0.000000040 mol/l
= 40 nmol/l

350

Urea

2.0

2
1

(∏ 12.87)

0.5–2.0
ng/dl

Triglycerides
target

< 1.5
mmol/l

3.5

3

0.5

(¥ 12.87)

0

0

5.0

8

6

0

Thyroxine (T4)

7
2.0

0

pH = –log10 [H ] in moles
e.g. 100nmol/l
nmol/l
= –log10 0.000000 = pH 7.0

8.0

400

6

< 110
mg/dl

35

9

5

7

60

20

0.6–1.3
mg/dl

15

3.5

4

40

(∏ 88.4)

(¥ 0.056)

600

11
100

(¥ 88.4)

50

0

SI/mass unit conversions  9


1

Acids, bases and hydrogen ions (protons)

Definition of pH
pH is defined as “the negative logarithm to the base 10 of the hydrogen ion concentration”,

10,000 ¥ 100,000 = 1,000,000,000 = 109
or
104 ¥ 105 = 109
(adding powers is the same as multiplying the original number)

pH = − log10 [H + ]

x
Log –y = log x – log y

For example, at pH 7.0, the hydrogen ion concentration is
0.000 000 1 mmoles/litre or 10−7 mmol/l.
The log10 of 0.000 0001 is − 7.0

1
Log –x = – log x
Figure 1.1  Revision of logarithms.

Therefore, the negative log10 is −(−7.0), i.e. +7.0 and hence the pH
is 7.0.

Number

Equivalent as 10
to the power “n”

Logarithm10

1000

103

3.0

100

102

2.0

10

101

1.0

1

100

0

0.1

10–1

–1.0

0.01

10–2

–2.0

0.000 000 1

10–7

–7.0

Number

Logarithm10

1
2
3
4
5
6
7
8
9
10
20
30
200
2000

0
0.301
0.477
0.602
0.699
0.778
0.845
0.903
0.954
1.0
1.301
1.477
2.301
3.301

Figure 1.2  Examples of numbers and their logarithms.

Units
1
0.001
0.000 001
0.000 000 001

Mole per litre
Mole per litre
Mole per litre
Mole per litre

Alternative representation

Definition of a base:

1 mol/l
1 mmol/l
1 µmol/l
1 nmol/l

A base is a substance that accepts a proton (i.e. a hydrogen
ion, H+) to form an acid, e.g. lactate is a conjugate base that
accepts a proton to form lactic acid

Figure 1.3  Understanding units.

Definition of an acid:
An acid is a compound that dissociates in water to release a
proton (i.e. a hydrogen ion, H+), e.g. lactic acid
A strong acid
(e.g. hydrochloric acid) is one that readily dissociates in water
to release a proton.

pH value
pH 1

Equivalent in other concentration units
0.1 Moles hydrogen ions/litre, or
10–1 Moles hydrogen ions/litre, or
10–1 g hydrogen ions per litre

pH 14

A weak acid
(e.g. uric acid) is one that does not readily dissociate in water
(e.g. to form urate and a proton)
Figure 1.4  Brønsted and Lowry definition of acids and bases.

0.000 000 000 000 01 Moles/litre, or
10–14 Moles hydrogen ions/litre, or
10–14 g hydrogen ions /litre

Figure 1.5  pH and equivalent values.

10  Medical Biochemistry at a Glance, Third Edition. J. G. Salway. © 2012 John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.


Acidotic arterial blood pH values
pH 6.8

Clinical examples

160 nmol/l

pH 6.9

130 nmol/l

pH 7.0

100 nmol/l

pH 7.1

80 nmol/l

pH 7.2

63 nmol/l

pH 7.3

50 nmol/l

metabolic acidosis,
e.g. diabetic ketoacidosis,
renal tubular acidosis

45 nmol/l

pH 7.36

44 nmol/l

pH 7.38

42 nmol/l

pH 7.40

40 nmol/l

pH 7.42

38 nmol/l

pH 7.44

36 nmol/l

pH 7.45

35 nmol/l

Alkalotic arterial blood pH values

normal arterial
blood pH

Clinical examples

32 nmol/l

pH 7.6

26 nmol/l

pH 7.7

20 nmol/l

metabolic alkalosis

pH 7.8

16 nmol/l

respiratory alkalosis

13 nmol/l

pH 8.0

10 nmol/l

A weak acid dissociates as shown:
HB
weak acid

H+ +
B−
proton + conjugate base

where HB is the weak acid that dissociates to a proton H+ and its conjugate base B−. NB Traditionally authors refer to the conjugate base
as “A−”, i.e. the initial letter of acid, which is perhaps confusing.
Therefore from the Law of Mass Action where K = dissociation
constant:

pH range is
7.35 to 7.45
(45 to 35
nMoles H+/litre)

pH 7.5

pH 7.9

The Henderson–Hasselbalch equation

respiratory acidosis

Normal arterial blood pH values
pH 7.35

Similarly, an increase in pH from pH 7.40 to pH 7.70 represents a fall
in H+ concentration from 40 nmol/l to 20 nmol/l.

K=

[H + ] + [ B− ]
[HB]

Taking logs:
log K = log[H + ] + log[ B− ] − log[HB]

Figure 1.6  Examples of pH values seen in clinical practice.

What is pH?
pH is “the “power of hydrogen”. It represents “the negative loga­
rithm10 of the hydrogen ion concentration”. So why make things so
complicated: why not use the plain and simple “hydrogen ion concen­
tration”? Well, the concept was invented by a chemist for chemists
and has advantages in chemistry laboratories. In clinical practice we

are concerned with arterial values between pH 6.9 and 7.9. However,
chemists need to span the entire range of pH values from pH 1 to pH
14. Values in terms of pH enable a convenient compression of numbers
compared with the alternative which would be extremely wide-ranging
as shown in Fig. 1.3. Figure 1.6 shows the normal reference range for
pH in blood and, in extremis, fatal ranges that may be seen in acidotic
or alkalotic diseases.

The pH scale is not linear
“The patient’s blood pH has changed by 0.3 pH unit” means it has
doubled (or halved) in value.
It is sometimes stated that “the patient’s arterial blood pH has
increased/decreased by, for example, 0.2 pH unit”. However, notice
that because of the logarithmic scale, this can misrepresent the true
change in traditional concentration units. For example, a fall of 0.2
pH units from pH 7.20 to pH 7.00 represents 37 nmol/l, whereas a
decrease from pH 7.00 to pH 6.8 represents a change of 60 nmol/l.
Also note that because the log10 of 2 = 0.3 (that is 2 = 100.3), a
decrease in pH by 0.3, e.g. from pH 7.40 to pH 7.10, represents a
two-fold increase in H+ concentration, i.e. from 40 nmol/l to 80 nmol/l.

∴ − log[ H + ] = − log K + log[ B− ] − log[HB]
i.e. pH = pK + log

[ B− ]
[HB]

Hence the Henderson–Hasselbalch equation:
pH = pK + log

[conjugate base]
[acid ]

Clinical relevance of the Henderson–
Hasselbalch equation
This is illustrated by respiratory acidosis and respiratory alkalosis. The
equation shows that:
pH = pK + log

[conjugate base]
[acid ]

Therefore in the case of the bicarbonate buffer system:
pH ∝ log

[HCO3 − ]
pCO2

Or, alternatively, the hydrogen ion concentration [H + ] ∝

pCO2
.
[HCO3 − ]

In other words, the hydrogen ion concentration is proportional to the
ratio of the amount of CO2 to bicarbonate concentration in the blood.
Hence, in hypercapnia (high blood CO2 concentration) such as in
respiratory acidosis, the ratio of pCO2 to HCO3− is abnormally high,
therefore the [H+] is high (i.e. pH is low).
Alternatively, hypocapnia caused by hyperventilation results in

respiratory alkalosis. In this condition, low blood CO2 concentra­
tions prevail so the hydrogen ion concentration [H+] is low (i.e. pH is
high).
The clinical relevance of pH and buffers will be described further
in Chapters 2–5.

Acids, bases and hydrogen ions (protons)  Acids, bases and pH  11


2

Understanding pH

Why do so many students have difficulty
understanding acid/base theory?
The arcane jargon used in acid/base theory bewilders

1962 Creese et al. wrote in the Lancet*: “There is a bewildering
variety of pseudoscientific jargon in medical writing on this subject.”
Difficulties arise because of this antiquated nomenclature, which is
illustrated by the dialogue below:

Acid/base theory is often considered a difficult subject. It involves an
understanding of acids and their ability to dissociate to form a conjugate base and hydrogen ions H+ (which are “protons”). As long ago as

* Creese R, Neil MW, Ledingham JM, Vere DW (1962) The terminology of
acid–base regulation. Lancet i, 419.

Lactic acid almost completely dissociates at normal blood pH
to form its conjugate base lactate and a proton (H+).

(Professor scribbles the structures on the back of an envelope):

The patient in intensive care with lactic acidosis pH 7.15, has
an arterial blood lactate of 5.4 mmol/l. What’s the
difference between lactic acid and lactate?
Student

Professor
Oh, so if the lactic acid is almost completely
dissociated does that mean there is very little
lactic acid present in blood in lactic acidosis?

Student

COOH

COO–

CHOH

CHOH

CH3

CH3

lactic acid

lactate + proton

+

H+

Well, yes. At pH 7.15 I calculate from the Henderson–Hasselbalch equation that there
are 2000 molecules of lactate for each molecule of lactic acid (see the Professor’s calculation below)
lactate
[B–] At pH 7.15, given the pK for lactic acid is 3.85 then
pH = pK + log ––––
7.15 = 3.85 + log ––––––––
[HB]
lactic acid
Professor

Well, so is it the supranormal
concentration of the
conjugate base lactate which
is present in the blood?

lactate
log –––––––– = 7.15 – 3.85 = 3.30
lactic acid

This means that at pH 7.15, there are 2000 molecules of lactate for each molecule of lactic acid,
or the proportion of lactic acid is a trivial 0.05%

Well, yes

Student
And is it this supranormal

concentration of the lactate
which is potentially fatal?

Professor
No. In fact, lactate is a “good” molecule.
It’s a useful metabolic precursor for gluconeogenesis.
It is the supranormal concentration of protons which is harmful

Student
Oh, I see……and the higher
the concentration of
protons, the lower the pH

lactate
Therefore taking antilogs, ––––––––– = 2000
lactic acid

Professor
Exactly, since pH is the negative logarithm to the base
10 of the hydrogen ion (i.e. proton) concentration

Student
Professor

(sensing victory) So, this means that when we say
the arterial blood is acidic, paradoxically there is
very little acid present …..Therefore, wouldn’t it be
better to call this a “hyperprotonic” solution?
Student
Therefore, in so-called “lactic acidosis”

we have excess of the conjugate base lactate and of
protons generated by the dissociation, i.e. absence,
of lactic acid. ………… Wouldn’t it be more
accurate to call this condition,
“lactate hyperprotonaemia ?”.

Hmmm, well…. Err.
Professor

Well, I suppose so but it will never catch on!

Student
Professor
12  Medical Biochemistry at a Glance, Third Edition. J. G. Salway. © 2012 John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.