Clinical Chemistry

381 Pages·2020·6.087 MB·English

by  William Marshall, Márta Lapsley, Andrew Day, Kate Shipman

Clinical Chemistry
Ninth Edition
William J. Marshall
MA PhD MSc MB BS FRCP FRCPath FRCPEdin FRSB FRSC
Emeritus Reader in Clinical Biochemistry, King’s College London;
formerly Consultant Clinical Biochemist and Director of Pathology,
The London Clinic, London, UK
Marta Lapsley
MB BCh BAO MD FRCPath
Formerly Consultant Chemical Pathologist,
Epsom and St Helier University Hospitals NHS Trust, Epsom, Surrey, UK
Andrew Day
MA MSc MB BS FRCPath
Consultant in Clinical Biochemistry and Metabolic Medicine,
University Hospitals Bristol NHS Foundation Trust, Bristol, UK
Kate Shipman
MA BMBCh MRCP FRCPath
Consultant Chemical Pathologist, Western Sussex NHS Foundation Trust, Chichester, UK
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Elsevier
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St. Louis, Missouri 63043
CLINICAL CHEMISTRY, NINTH EDITION ISBN: 978-0-702-0-7936-8
INTERNATIONAL EDITION ISBN: 978-0-702-0-7930-6
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Preface
The information resources currently available to students are varied and numerous. However,
despite the widespread availability of electronic materials, the appeal of a book has not lessened.
This tangible tool remains popular, and with the ninth edition of this text and online extras, we
hope to fulfil all the requirements of those seeking an introduction to clinical chemistry. Please
do look at the electronic version for interactive diagrams and multiple-choice questions at varying
levels of complexity.
This book was originally written primarily for medical students. However, the utility of a succinct
review of the topic has been recognized by many disciplines, both clinical and scientific, and at all
stages of training. With the help of comments received from readers around the world, we hope that
we fulfil such varied requirements. Please do continue to provide us with your invaluable feedback
so that we can further improve the book in future editions.
Each chapter includes a summary of the basic biochemistry and physiology upon which under-
standing clinical biochemistry depends. The nature, choice, use and limitations of laboratory inves-
tigations naturally comprise the bulk of each chapter, but clinical biochemistry is only one part
of laboratory medicine, and laboratory tests comprise only one group among the many types of
investigation available to support diagnosis and management. Other investigations—for example
imaging—are mentioned and overviews of management options are provided; however, we stress
that this book is not, and is not intended to be, a textbook of metabolic medicine.
Maybe we should not be surprised by the considerable number and rate of developments since
the previous edition, but progress never ceases to amaze. In preparing this edition, there has been
significant movement of material between chapters as well as an update and deletion of obsolete
material, we hope in a logical manner. Throughout the text, there are new ‘red flag sections’ indi-
cated by an exclamation mark heading in their respective boxes to emphasise biochemical findings
that almost always indicate serious pathology.
We are fortunate enough to have a global readership, but when referring to best practice, UK
guidelines are primarily used. Such ‘local’ guidance is clearly highlighted, but it should be borne in
mind that population and service setup variations throughout the world may result in differences
between what is considered gold standard and what is practical to provide.
At Elsevier, we have been ably supported by Jeremy Bowes and his fantastic team whose patience
and professionalism have made the process a joy. Their cheerful encouragement and expertise have
been much appreciated. We are indebted to the designers, copyeditor and indexer whose work has
been essential to the production of the book.
At home, once again, Wendy (Marshall), Michèle (Day), Michael (Lapsley) and Alexa (Shipman)
have been unstinting in their support and encouragement. We thank them for their significant,
albeit indirect, contribution to this book.
William J. Marshall
Andrew Day
Marta Lapsley
Kate Shipman
v
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Further Reading
To seek the most up-to-date information on a topic, readers are recommended to use one of the
bibliographic databases that specialize in medical and scientific journals, for example Medline
(the database of the National Library of Medicine in the USA, which encompasses references
to reviews and papers published in more than 5000 journals and can be accessed via PubMed,
www.ncbi.nlm.nih.gov/pubmed/).
Journals that publish articles and reviews relating to clinical chemistry include Annals of Clini-
cal Biochemistry and Clinical Chemistry. Each issue of Endocrine and Metabolism Clinics of North
America comprises sets of reviews on related topics, most of which are of direct relevance to
clinical chemistry. General medical journals, such as the British Medical Journal, Lancet and New
England Journal of Medicine, carry editorials and reviews of topics related to clinical chemistry
from time to time. The monthly issues of Medicine together comprise a textbook of medicine,
which is updated on a 3-year cycle and is highly recommended.
Many organizations produce guidelines for the investigation and treatment of various disor-
ders, which are usually available online. In the UK, these include the National Institute for Health
and Care Excellence (NICE, www.nice.org.uk) and the Scottish Intercollegiate Guidelines Network
(SIGN, www.sign.ac.uk). A number of specialist societies produce and regularly update guidelines
that are of relevance to the material discussed in this book. Some of these are listed below, and
readers are encouraged to visit their websites for further information. Information about individual
laboratory tests is available from Lab Tests Online-UK (http://labtestsonline.org.uk), a non-com-
mercial website organized by the Association for Clinical Biochemistry and Laboratory Medicine.
And we would particularly draw attention to the American Association for Clinical Chemistry
that hosts the Clinical Chemistry Trainee Council (https://www.aacc.org/clinical-chemistry-trainee-
council). This fantastic and free resource is a repository for cases, questions, podcasts, lectures and
guidance provided in several languages for trainees in clinical chemistry throughout the world.
Some specialist organizations that produce clinical guidelines
American Association of Clinical Endocrinologists www.aace.com
Association for Clinical Biochemistry and Laboratory www.acb.org.uk
Medicine
British Association for Enteral and Parenteral Nutrition www.bapen.org.uk
British Cardiovascular Society www.bcs.com
British Endocrine Society www.endocrinology.org
British Inherited Metabolic Diseases Group www.bimdg.org.uk
British Society of Gastroenterology www.bsg.org.uk
British Society for H aematology www.b-s-h.org.uk
British Society for Rheumatology www.rheumatology.org.uk
British Thyroid Association www.british-thyroid-association.org
vii
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will appear in color in all electronic versions of this book.
Further Reading
Diabetes UK www.diabetes.org.uk
European Atherosclerosis Society www.eas-society.org
Endocrine Society www.endocrine.org
European Porphyria Network www.porphyria.eu
European Renal Best Practice Group www.european-renal-best-practice.org
European Society of Cardiology www.escardio.org
Imperial Centre for Endocrinology (Endocrine Bible) www.imperialendo.com/for-doctors/
endocrine-bible
National Metabolic Biochemistry Network www.metbio.net
Renal Association www.renal.org
viii
These proofs may contain color figures. Those figures may print black and white in the final printed book if a color print product has not been planned. The color figures
will appear in color in all electronic versions of this book.
1
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1
Chapter | 1 | An introduction to biochemistry and cell biology
emission of radiation at a specific wavelength. Many general, assays become less precise at low concentrations,
enzyme-based methods ultimately depend on the conver- and in some cases, it may (at least at present) be impossible
sion of NAD+ to NADH (or vice versa) and consequent to measure accurately such concentrations even if they are
change in the absorption of radiation at 360 nm. (Note biologically relevant. For this reason, some reference inter-
that in this context, enzymes are being used as reagents: it vals (the range of values typical of a defined population, see
is not the enzyme activity that is being measured, although Chapter 2) may not have a defined lower limit. It is then
many enzymes are measured using such techniques so that usual to give the lower limit as zero, but it is more informa-
the reaction mixture contains both the enzyme being mea- tive to quote the lower limit of detection – that is, the lowest
sured and the enzyme[s] used to generate the signal that is measurable concentration that can be reliably distinguished
detected by the analytical instrument.) from zero. These limitations can be classified as chemical or
Ion-selective electrodes are used for measuring ions physical. This is an important consideration in attempting
such as Na+, K+ and H+. These work on the principle that to measure reduced concentrations of substances, where the
the analyte generates a potential difference (voltage) across limitations of the method may prevent a distinction being
a selective membrane (i.e. one that is permeable only to the made between a normal and a reduced value.
ion in question), which can be measured using a sensitive Laboratory measurements are made to detect and
voltameter. Measurement of the partial pressure of carbon monitor pathological changes, but it is important to be
dioxide (Pco2) also uses an ion-selective electrode, and that aware that many measurements are affected by a range
of oxygen (Po2) uses a related technique. of physiological and environmental factors (e.g. time of
Atomic emission spectroscopy—the detection of the day, relation to meals), and these must be borne in mind
radiation emitted by a substance when it is heated in a flame when interpreting the result of laboratory tests. This topic is
(the bright red colour produced in strontium-c ontaining discussed further in Chapter 2. Finally, drugs are a frequent
fireworks is a familiar example)—was previously widely used cause of assay interference, either through a direct effect on
to measure sodium, potassium and lithium, but it has been the assay itself (i.e. behaving like the analyte of interest, an
largely superseded by the use of ion-selective electrodes. example being prednisolone, which reacts in many assays
Atomic absorption spectroscopy, where the absorption of for cortisol) or through a pharmacological effect (certain
radiation of a specific wavelength by a substance is quanti- diuretics that cause hypokalaemia, for example). Further
fied, is still widely used for measuring the concentration of instances are discussed where relevant in the ensuing chap-
metals such as copper, although more accurate and reliable ters of this book.
techniques are now available and are typically used in labo- Particular problems are posed by immunoassays,
ratories that specialize in such investigations. widely used for measuring hormones (both peptide and
Separation techniques are widely used in clinical steroid hormones), other peptides, proteins (including
biochemistry either alone (as with capillary zone electro- most tumour markers) and some drugs. Immunoassays
phoresis to detect paraproteins; see Chapter 16) or as a are based on antibodies that are chosen to react specifi-
preliminary to measurement by one of many techniques cally with individual molecular species. Two major prob-
depending on the nature of the analyte. The introduction lems arise from this: first, antibodies may (and often do)
of chromatography coupled to detection by mass spec- lack specificity (i.e. they may bind to structurally closely
trometry has been of particular importance in measuring related molecules to that of interest – e.g. 11-deoxycorti-
metabolites of interest in relation to inherited metabolic sol is detected by many cortisol assays); and second, the
diseases, drugs and hormones, and it allows accurate mea- antibodies developed and used by different suppliers of
surements at very low concentrations. analytical instruments may react with different epitopes on
To be of value, analytical methods must be both specific the surface of the target molecule. Assay interference and
(measuring only the substance of interest) and sensitive variability between different manufacturers’ methods is a
(able to measure biologically relevant concentrations with potential problem with all immunoassays but is particu-
precision [i.e. reproducibly] and accurately [i.e. correctly]). larly so with tumour markers. 
Note that the terms ‘sensitivity’ and ‘specificity’ are used
in other contexts in clinical biochemistry, as discussed in
Chapter 2. Ions and Molecules of Biological
Whereas some substances measured in clinical bio- Importance
chemistry laboratories are present in serum or urine (the
most frequent fluids in which measurements are made) at
relatively high concentrations (e.g. sodium ∼140 mmol/L, A considerable range of substances are of biological impor-
albumin 40 g/L), others, particularly some hormones, are tance. Ions are atoms or molecules that carry an electric
present at only very low concentrations (e.g. picomolar, that charge, either overall positive or negative (or sometimes
is, 10−12 mol/L). This poses huge technical challenges. In carrying charges that cancel each other out, e.g. one
2
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will appear in color in all electronic versions of this book.
An introduction to biochemistry and cell biology Chapter | 1 |
positive and one negative charge: these are termed ‘zwit-
terions’). Important chemical groups that can readily ion- (cid:38)(cid:43) (cid:50)(cid:43) (cid:38)(cid:43) (cid:50)(cid:43)
(cid:21) (cid:21)
ize include amino (−NH2) and carboxyl (−COOH) groups: (cid:50) (cid:50)
amino groups readily gain a proton (i.e. a hydrogen ion, (cid:43) (cid:43) (cid:43)(cid:50) (cid:50)(cid:43)
(cid:43) (cid:43)
H+) to become −NH +, whereas carboxyl groups readily
3
lose a proton to become −COO−. Groups that can release (cid:50)(cid:43) (cid:43) (cid:50)(cid:43) (cid:43)
(cid:43)(cid:50) (cid:50)(cid:43) (cid:43) (cid:43)
a proton are termed ‘acidic’; those that can gain a pro-
ton are called ‘basic’. Whether a molecule forms an ion
(cid:43) (cid:50)(cid:43) (cid:43) (cid:50)(cid:43)
depends on the prevailing hydrogen ion concentration.
Hydroxyl (−OH) groups do not ionize but can interact (cid:42)(cid:79)(cid:88)(cid:70)(cid:82)(cid:86)(cid:72) (cid:42)(cid:68)(cid:79)(cid:68)(cid:70)(cid:87)(cid:82)(cid:86)(cid:72)
with other hydroxyl groups (including those in water) in
a process called ‘hydrogen bonding’. Substances that are
capable of becoming charged are termed ‘polar’. Water is a
strongly polar molecule (capable of dissociation into posi- (cid:43)(cid:50)(cid:38)(cid:43)(cid:21) (cid:50) (cid:50)(cid:43) (cid:43)(cid:50)(cid:38)(cid:43)(cid:21) (cid:50) (cid:50)(cid:43)
tively charged hydrogen ions (H+) and negatively charged
hydroxyl ions (OH−). Because of this, polar entities are (cid:43) (cid:43) (cid:43) (cid:43) (cid:43) (cid:43) (cid:43) (cid:43)
typically soluble in aqueous media such as plasma but
can only cross cell and intracellular membranes through
(cid:50)(cid:43) (cid:50)(cid:43) (cid:50)(cid:43) (cid:43)
special channels, access through which is often subject to
control. This is because the outward-facing surfaces of such (cid:53)(cid:76)(cid:69)(cid:82)(cid:86)(cid:72) (cid:39)(cid:72)(cid:82)(cid:91)(cid:92)(cid:85)(cid:76)(cid:69)(cid:82)(cid:86)(cid:72)
membranes are non-polar. On the other hand, non-polar
entities are insoluble in aqueous media, and in the plasma
circulate bound to soluble proteins, for example, albumin.
(cid:38)(cid:43) (cid:50)(cid:43) (cid:43) (cid:50)(cid:43)
However, they can typically cross cell and intracellular (cid:21)
(cid:50)
membranes unaided. Many molecules have both polar and
(cid:43)(cid:50) (cid:50)(cid:43)
non-polar regions. In proteins, for example, the non-polar (cid:43) (cid:50) (cid:50)(cid:43) (cid:43)
(also termed ‘lipophilic’ or ‘hydrophobic’) regions tend to
(cid:50)(cid:43) (cid:43) (cid:43)
be in the interior of the molecule, whereas the polar (lipo- (cid:43) (cid:43) (cid:43) (cid:43)
(cid:50)
phobic, hydrophilic) regions face outwards. The same is
true of molecular aggregates, for example, lipoproteins (see (cid:43) (cid:50)(cid:43) (cid:38)(cid:43)(cid:21)(cid:50)(cid:43)
Chapter 17). (cid:42)(cid:68)(cid:79)(cid:68)(cid:70)(cid:87)(cid:82)(cid:86)(cid:72) (cid:42)(cid:79)(cid:88)(cid:70)(cid:82)(cid:86)(cid:72)
Small ions of biological importance include sodium
(cid:47)(cid:68)(cid:70)(cid:87)(cid:82)(cid:86)(cid:72)
and potassium, which carry single positive charges, and
calcium and magnesium, which carry two positive charges.
Positively charged ions are termed cations. Hydrogen ions
Fig. 1.1 Examples of single carbohydrates (monosaccharides)
(single positive charge) are particularly important cations: and a disaccharide (lactose, comprising one molecule of glu-
their concentration in a fluid determines the extent of ion- cose and one of galactose). Glucose and galactose are hexoses
ization of all polar entities. Negatively charged ions include (six carbon atoms); ribose and deoxyribose are pentoses (five
chloride and bicarbonate (one charge) and phosphate (one, carbon atoms).
two or three charges, according to the prevailing hydrogen
ion concentration). These are collectively known as anions. a phosphate residue and a purine or pyrimidine, Fig. 1.2).
Several groups of small molecules are of major biologi- Individual nucleotides (e.g. adenosine triphosphate [ATP])
cal importance. Simple carbohydrates (sugars, Fig. 1.1), play a major role in providing energy to power chemical
such as glucose, fructose, ribose and deoxyribose, consist reactions in cells. Simple sugars can bind to other sugars to
of carbon, hydrogen and oxygen. These are readily solu- form disaccharides, trisaccharides and polysaccharides. The
ble in water because of the interaction of their hydroxyl latter include glycogen, an important energy store in the
groups with water molecules (H−O−H). Carbohydrates body, starch and dietary fibre (Fig. 1.3).
are important energy sources and, in the case of ribose and Fatty acids also comprise carbon, hydrogen and oxygen,
deoxyribose, are components of nucleic acids (deoxyribo- and they consist of a chain of hydrogenated carbon atoms
nucleic acid [DNA], the repository of genetic information, of variable length (an alkyl chain) with a terminal carboxyl
and ribonucleic acid [RNA], important in the translation group (Fig. 1.4). Short-chain fatty acids are soluble in
of genetic information into the synthesis of functional water, but solubility decreases with increasing length of the
proteins, respectively). Nucleic acids are polymers of carbon chain. Fatty acids can be either saturated or unsat-
nucleotides (comprising ribose or deoxyribose linked to urated. In saturated fatty acids, each carbon atom in the
3
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will appear in color in all electronic versions of this book.
Chapter | 1 | An introduction to biochemistry and cell biology
(cid:49)(cid:43)
(cid:21)
(cid:43)(cid:38) (cid:38)(cid:43) (cid:38)(cid:50)(cid:50)(cid:43) (cid:43)(cid:38) (cid:38)(cid:43) (cid:38)(cid:50)(cid:50)(cid:43)
(cid:22) (cid:21) (cid:22) (cid:21)
(cid:49) (cid:49) (cid:20)(cid:23) (cid:20)(cid:25)
(cid:50)(cid:43) (cid:43) (cid:51)(cid:68)(cid:79)(cid:80)(cid:76)(cid:87)(cid:76)(cid:70)(cid:3)(cid:68)(cid:70)(cid:76)(cid:71) (cid:54)(cid:87)(cid:72)(cid:68)(cid:85)(cid:76)(cid:70)(cid:3)(cid:68)(cid:70)(cid:76)(cid:71)
(cid:49) (cid:49) (cid:43)
(cid:43)(cid:50) (cid:51) (cid:50) (cid:38)(cid:43) (cid:50)
(cid:21)
(cid:50) (cid:36)(cid:71)(cid:72)(cid:81)(cid:76)(cid:81)(cid:72) (cid:43)(cid:38) (cid:38)(cid:43) (cid:38)(cid:43) (cid:38)(cid:43) (cid:38)(cid:43) (cid:38)(cid:50)(cid:50)(cid:43)
(cid:22) (cid:21) (cid:21)
(cid:43) (cid:43) (cid:43) (cid:43) (cid:26) (cid:26)
(cid:51)(cid:75)(cid:82)(cid:86)(cid:83)(cid:75)(cid:68)(cid:87)(cid:72) (cid:50)(cid:79)(cid:72)(cid:76)(cid:70)(cid:3)(cid:68)(cid:70)(cid:76)(cid:71)
(cid:50)(cid:43) (cid:43)
(cid:39)(cid:72)(cid:82)(cid:91)(cid:92)(cid:85)(cid:76)(cid:69)(cid:82)(cid:86)(cid:72) (cid:43)(cid:38) (cid:38)(cid:43) (cid:38)(cid:43) (cid:38)(cid:43) (cid:38)(cid:43) (cid:38)(cid:43) (cid:38)(cid:43) (cid:38)(cid:43) (cid:38)(cid:50)(cid:50)(cid:43)
(cid:22) (cid:21) (cid:21) (cid:21)
(cid:23) (cid:26)
Fig. 1.2 A nucleotide, adenosine monophosphate, compris- (cid:47)(cid:76)(cid:81)(cid:82)(cid:79)(cid:72)(cid:76)(cid:70)(cid:3)(cid:68)(cid:70)(cid:76)(cid:71)
ing a phosphorylated pentose linked to a nitrogenous base,
in this case, adenine. DNA and RNA consist of linear chains of
nucleotides. In DNA, the pentose is deoxyribose, in RNA, it is Fig. 1.4 Long-chain fatty acids. The most commonly occurring
ribose. The base can be a purine, either adenine or guanine, in the human body are palmitic and stearic acids. Oleic acid is a
or a pyrimidine (thymine or cytosine in DNA, cytosine or uracil monounsaturated fatty acid; linoleic acid is a polyunsaturated
in RNA). The double-stranded structure of DNA is maintained fatty acid.
through hydrogen bonding between pairs of bases.
(cid:38)(cid:43) (cid:50)(cid:43) (cid:38)(cid:43) (cid:50) (cid:38)(cid:50) (cid:38)(cid:43) (cid:38)(cid:43)
(cid:21) (cid:21) (cid:21) (cid:22)
(cid:38)(cid:43) (cid:50)(cid:43) (cid:38)(cid:43) (cid:50)(cid:43) (cid:38)(cid:43) (cid:50)(cid:43) (cid:81)
(cid:21) (cid:21) (cid:21)
(cid:50) (cid:50) (cid:50) (cid:38)(cid:43)(cid:50)(cid:43) (cid:38)(cid:43) (cid:50) (cid:38)(cid:50) (cid:38)(cid:43) (cid:38)(cid:43)
(cid:43) (cid:43) (cid:43) (cid:43) (cid:43) (cid:43) (cid:21) (cid:22)
(cid:43) (cid:43) (cid:43) (cid:81)
(cid:50)(cid:43) (cid:43) (cid:50) (cid:50)(cid:43) (cid:43) (cid:50) (cid:50)(cid:43) (cid:43) (cid:38)(cid:43) (cid:50)(cid:43) (cid:38)(cid:43) (cid:50) (cid:38)(cid:50) (cid:38)(cid:43) (cid:38)(cid:43)
(cid:43)(cid:50) (cid:50)(cid:43) (cid:21) (cid:21) (cid:21) (cid:22)
(cid:81)
(cid:43) (cid:50)(cid:43) (cid:43) (cid:50)(cid:43) (cid:81) (cid:43) (cid:50)(cid:43) (cid:42)(cid:79)(cid:92)(cid:70)(cid:72)(cid:85)(cid:82)(cid:79) (cid:36)(cid:3)(cid:87)(cid:85)(cid:76)(cid:68)(cid:70)(cid:92)(cid:79)(cid:74)(cid:79)(cid:92)(cid:72)(cid:85)(cid:82)(cid:79)
(cid:42)(cid:79)(cid:88)(cid:70)(cid:82)(cid:86)(cid:72) (cid:42)(cid:79)(cid:88)(cid:70)(cid:82)(cid:86)(cid:72) (cid:42)(cid:79)(cid:88)(cid:70)(cid:82)(cid:86)(cid:72)
Fig. 1.5 Glycerol and triacylglycerols (triglycerides). In tripal-
mityl glycerol, n = 14. In any one molecule, the fatty acids are
Fig. 1.3 Amylose, a polysaccharide, is a linear polymer of glu-
always the same.
cose and a component of starch. Glycogen is also a polymer of
glucose but has a branched structure.
Amino acids contain at least one carboxyl and one
chain carries two hydrogen atoms—that is, is a methylene amino group (Fig. 1.7). When there is one of each, an amino
group—except for the first, which carries three (a methyl acid is said to be neutral: those with two carboxyl and one
group): the carbon atoms in the chain are linked by single amino group are acidic, and those with one carboxyl and
covalent bonds. In unsaturated fatty acids, an even num- two amino groups are basic. With the exception of glycine,
ber of adjacent carbon atoms carry only one hydrogen, and all amino acids contain a carbon atom with four different
these carbons are linked by double bonds. substituents (i.e. covalently bound to four different groups).
Alcohols are substances that carry one or more hydroxyl These groups can be arranged spatially in two different ways;
groups. The simplest is methanol, CH OH. The most these are termed stereoisomers. They have the same chemical
3
important in mammalian biochemistry is glycerol (Fig. composition, but their physical structure is different. Stereo-
1.5), a trihydric (three −OH groups) alcohol, which can isomers are termed either d- or l-. All amino acids that occur
combine with fatty acids (esterification) to form triacyl- in humans (and other mammals) are l-isomers. Some amino
glycerols (often referred to as triglycerides, see Fig. 1.5). acids can be synthesized in the body; others cannot and must
These substances are all discussed in detail in Chapter 17. be provided in the diet. The former amino acids are termed
They are important for energy storage. Entities in which ‘non-essential’ and the latter are termed ‘essential’. Amino
two of the hydroxyls of glycerol are combined with fatty acids can combine together to form peptides (Fig. 1.8). These
acids and the third with a phosphate- or nitrogen-contain- can comprise small or large numbers of amino acids (oligo-
ing substance are important structurally, particularly in cell peptides and polypeptides, respectively). The former peptides
and intracellular membranes (Fig. 1.6). include many hormones, growth factors and other signalling
4
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