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Biochemistry and Molecular Biology 5th Revised edition [Pehme köide]

(King's College London), (Department of Biochemistry, Flinders University, Adelaide, Australia), (King's College London), (Department of Biochemistry, University of Adelaide, Australia)
  • Formaat: Paperback / softback, 624 pages, kõrgus x laius x paksus: 267x208x25 mm, kaal: 1218 g
  • Ilmumisaeg: 30-Jan-2014
  • Kirjastus: Oxford University Press
  • ISBN-10: 0199609497
  • ISBN-13: 9780199609499
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  • Formaat: Paperback / softback, 624 pages, kõrgus x laius x paksus: 267x208x25 mm, kaal: 1218 g
  • Ilmumisaeg: 30-Jan-2014
  • Kirjastus: Oxford University Press
  • ISBN-10: 0199609497
  • ISBN-13: 9780199609499
Teised raamatud teemal:
Now in its fifth edition Biochemistry and Molecular Biology features a new author team, who have retained the much-praised clarity of previous editions, while adding a more biomedical focus and incorporating a discussion of recent developments in research.

A new chapter on the general principles of nutrition emphasises the key principles underlying complex metabolic pathways, enabling students to appreciate an integrated view of human metabolism and nutrition. Also new to the fifth edition, a chapter on the control of gene expression reflects our increasing understanding of the importance and power of gene regulation.

With an integrated approach covering both biochemistry and molecular biology, complemented by frequent diagrams and clear explanations, and all presented in a broader cellular context, this text is the perfect introduction for any student new to the subject.

Online Resource Centre: The Online Resource Centre features:

For registered adopters of the book: · Figures from the book available to download

For students: · Further reading organised by chapter, linked to the book via QR codes · An extensive bank of multiple-choice questions for self-directed learning · Links to 3D molecular structures

Arvustused

Easy to read with good use of simple figures and plenty of internal cross-references to other chapters or relevant pages. I was impressed with the inclusion of some very up to date findings. * Dr Peter Morris, School of Life Sciences, Heriot-Watt University * I don't know of any other biology/biochemistry book that explains DNA replication as well as this one * Lynn Rogers, School of Molecular and Biomedical Science, Adelaide University * The style is very clear, logical and systematic. The diagrams complement the text well * Dr Momna Hejmadi, Department of Biology and Biochemistry, University of Bath *

Diseases and medically relevant topics xxiii
Abbreviations xxv
Part 1 Basic concepts of life
Chapter 1 The basic molecular themes of life
3(13)
All life forms are similar at the molecular level
3(1)
The energy cycle in life
4(1)
The laws of thermodynamics deal with energy
4(1)
Energy can be transformed from one state to another
5(1)
ATP (adenosine triphosphate) is the universal energy currency in life
5(1)
Types of molecules found in living cells
5(3)
Small molecules
6(1)
Macromolecules are made by polymerization of smaller units
7(1)
Protein and nucleic acid molecules have information content
7(1)
Proteins
8(1)
Catalysis of reactions by enzyme proteins is central to the existence of life
8(1)
What is the function of enzymes?
8(1)
Proteins work by molecular recognition
9(1)
Life is self-assembling due to molecular recognition by proteins
9(1)
Many proteins are molecular machines
9(1)
How can one class of molecule carry out so many tasks?
9(1)
Evolution of proteins
9(1)
Development of new genes
9(1)
DNA (deoxyribonucleic acid)
10(2)
DNA directs its own replication
10(1)
Genetic code
10(2)
Organization of the genome
12(1)
How did life start?
12(1)
The RNA world
13(1)
Proteomics and genomics
13(3)
Summary
13(2)
Further reading
15(1)
Problems
15(1)
Chapter 2 Cells and viruses
16(11)
Cells are the units of all living systems
16(1)
What determines the size of cells?
16(1)
Classification of organisms
16(7)
Prokaryotic cells
17(1)
Eukaryotic cells
18(3)
Basic types of eukaryotic cells
21(2)
Viruses
23(4)
Summary
25(1)
Further reading
26(1)
Problems
26(1)
Chapter 3 Energy considerations in biochemistry
27(18)
Energy considerations determine whether a chemical reaction is possible in the cell
27(1)
Reversible and irreversible reactions and G values
28(1)
The importance of irreversible reactions in the strategy of metabolism
29(1)
What is the significance of irreversible reactions in a metabolic pathway?
29(1)
How are G values obtained?
29(1)
Standard free energy values and equilibrium constants
30(1)
The release and utilization of free energy from food
30(1)
ATP is the universal energy intermediate in all life
31(5)
What are the structural features of high-energy phosphate compounds?
31(2)
The structure of ATP
33(1)
What transports the--- around the cell?
33(1)
How does ATP drive chemical work?
34(1)
How does ATP drive other types of work?
35(1)
High-energy phosphoryl groups are transferred by enzymes known as kinases
35(1)
Energy considerations in covalent and noncovalent bonds
36(2)
Noncovalent bonds are the basis of molecular recognition and self-assembly of life forms
36(1)
Noncovalent bonds are also important in the structures of individual protein molecules and other macromolecules
37(1)
Types of noncovalent bonds
37(1)
Ionic bonds
37(1)
Hydrogen bonds
37(1)
van der Waals forces
38(1)
Hydrophobic force
38(1)
Appendix: Buffers and pKa values
38(7)
pKa values and their relationship to buffers
39(1)
Summary
40(1)
Further reading
41(1)
Problems
41(4)
Part 2 Structure and function of proteins and membranes
Chapter 4 The structure of proteins
45(27)
Structures of the 20 amino acids used in protein synthesis
45(3)
The different levels of protein structure - primary, secondary, tertiary, and quaternary
48(7)
Primary structure of proteins
48(2)
Secondary structure of proteins
50(2)
Tertiary structure of proteins
52(3)
Quaternary structure of proteins
55(1)
Protein homologies and evolution
55(1)
Protein domains
56(1)
Domain shuffling
56(1)
Membrane proteins
56(1)
Conjugated proteins and post-translational modifications of proteins
56(1)
Extracellular matrix proteins
57(6)
Structure of collagens
57(2)
Structure of elastin
59(1)
Structure of proteoglycans
59(1)
Fibronectin and integrins connect the extracellular matrix to the interior of the cell
60(3)
Myoglobin and haemoglobin illustrate how protein structure is related to function
63(9)
Myoglobin
63(1)
Structure of haemoglobin
64(1)
Binding of oxygen to haemoglobin
64(1)
Theoretical models to explain protein allostery
65(1)
Mechanism of the allosteric change in haemoglobin
66(1)
The essential role of 2,3-bisphosphoglycerate (BPG) in haemoglobin function
66(2)
Effect of pH on oxygen binding to haemoglobin
68(1)
Summary
69(1)
Further reading
70(1)
Problems
71(1)
Chapter 5 Methods in protein investigation
72(15)
Purification of proteins
72(5)
Column chromatography
73(1)
SDS polyacrylamide gel electrophoresis (SDS-PAGE)
74(1)
Nondenaturing polyacrylamide gel electrophoresis
75(2)
The principles of mass spectrometry
77(1)
Mass spectrometers consist of three principal components
77(1)
Ionization methods for protein and peptide mass spectrometry
77(1)
Types of mass analysers
78(1)
Types of mass spectrometers
78(1)
Applications of mass spectrometry
78(1)
Molecular weight determination of proteins
78(1)
Identification of proteins using mass spectrometry without sequencing
79(1)
Identification of proteins by limited sequencing and database searching
79(1)
Analysis of post-translational modification of proteins
79(1)
Methods of sequencing protein
79(2)
Classical methods
79(1)
Sequence prediction of proteins from gene DNA sequences
79(1)
Sequencing by mass spectrometry
80(1)
Determination of the three-dimensional structure of proteins
81(1)
X-ray diffraction
81(1)
Nuclear magnetic resonance spectroscopy
81(1)
Homology modelling
82(1)
An exercise in obtaining a 3-D structure from a protein database
82(1)
Proteomics
82(1)
Bioinformatics and databases
83(4)
Summary
85(1)
Further reading
85(1)
Problems
85(2)
Chapter 6 Enzymes
87(16)
Enzyme catalysis
87(3)
The nature of enzyme catalysis
88(1)
The induced-fit mechanism of enzyme catalysis
89(1)
Enzyme kinetics
90(4)
Hyperbolic kinetics of a `classical' enzyme
90(2)
Allosteric enzymes
92(2)
General properties of enzymes
94(2)
Nomenclature of enzymes
94(1)
Isozymes
94(1)
Enzyme cofactors and activators
94(1)
Covalent modification of enzymes
94(1)
Effect of pH on enzymes
95(1)
Effect of temperature on enzymes
95(1)
Effect of inhibitors on enzymes
95(1)
Competitive and noncompetitive inhibitors
95(1)
Mechanism of enzyme catalysis
96(7)
Mechanism of the chymotrypsin reaction
96(1)
The catalytic triad of the active site
97(1)
The reactions at the catalytic site of chymotrypsin
98(1)
What is the function of the aspartate residue of the catalytic triad?
98(1)
Other serine proteases
99(1)
A brief description of other types of protease
100(1)
Summary
101(1)
Further reading
102(1)
Problems
102(1)
Chapter 7 The cell membrane and membrane proteins
103(24)
Basic lipid architecture of membranes
103(7)
The polar lipid constituents of cell membranes
103(2)
What are the polar groups attached to the phosphatidic acid?
105(2)
Membrane lipid nomenclature
107(1)
What is the advantage of having so many different types of membrane lipid?
107(1)
The fatty acid components of membrane lipids
108(1)
What is cholesterol doing in membranes?
108(1)
The self-sealing character of the lipid bilayer
109(1)
Permeability characteristics of the lipid bilayer
109(1)
Membrane proteins and membrane structure
110(1)
Structures of integral membrane proteins
111(2)
Anchoring of peripheral membrane proteins to membranes
112(1)
Glycoproteins
112(1)
Functions of membranes
113(14)
Membrane transport
113(3)
Passive transport or facilitated diffusion
116(1)
Gated ion channels
116(1)
Mechanism of the selectivity of the potassium channel
117(1)
Nerve-impulse transmission
118(1)
How does acetylcholine binding to a membrane receptor result in a nerve impulse?
119(3)
Myelinated neurons permit more rapid nerve-impulse transmission
122(1)
Role of the cell membrane in maintaining the shape of the cell
123(2)
Cell-cell interactions - tight junctions, gap junctions, and cellular adhesive proteins
125(1)
Summary
125(1)
Further reading
126(1)
Problems
126(1)
Chapter 8 Muscle contraction, the cytoskeleton, and molecular motors
127(20)
Muscle contraction
127(1)
A reminder of conformational changes in proteins
127(1)
Types of muscle cell and their energy supply
127(4)
Structure of skeletal striated muscle
128(2)
How does the myosin head convert the energy of ATP hydrolysis into mechanical force on the actin filament?
130(1)
Control of voluntary striated muscle
131(1)
How does Ca2+trigger contraction?
131(1)
Smooth muscle differs in structure and control from striated muscle
132(3)
Control of smooth muscle contractions
134(1)
The cytoskeleton
135(1)
An overview
135(1)
The cytoskeleton is in a constant dynamic state
136(1)
The role of actin and myosin in nonmuscle cells
136(2)
Assembly and collapse of actin filaments
137(1)
The role of actin and myosin in cell movement
138(1)
The role of actin and myosin in intracellulartransport of vesicles
138(1)
Microtubules, cell movement, and intracellular transport
138(2)
Intermediate filaments
140(7)
Summary
142(1)
Further reading
142(1)
Problems
143(4)
Part 3 Metabolism and nutrition
Chapter 9 General principles of nutrition
147(9)
The requirement for energy and nutrients
147(5)
Protein
148(1)
Fats
148(1)
Carbohydrates
149(1)
Vitamins
149(3)
Guidelines for a healthy diet
152(1)
Regulation of food intake
152(4)
Hunger appetite and satiety
152(1)
Integration of hunger and satiety signals by the hypothalamus
153(1)
Summary
154(1)
Further reading
155(1)
Problems
155(1)
Chapter 10 Food digestion, absorption, and distribution to the tissues
156(17)
Chemistry of foodstuffs
156(1)
Digestion and absorption
157(1)
Anatomy of the digestive tract
158(1)
What are the energy considerations in digestion and absorption?
158(1)
A major problem in digestion - why Doesn't the body digest itself?
158(1)
Digestion of proteins
158(3)
HCI production in the stomach
159(1)
Pepsin, the proteotytic enzyme or the stomach
159(1)
Completion of protein digestion in the small intestine
159(1)
Activation of the pancreatic proenzymes
160(1)
Absorption of amino acids into the bloodstream
160(1)
Digestion of carbohydrates
161(2)
Structure of carbohydrates
161(1)
Digestion of starch
161(1)
Digestion of sucrose
162(1)
Digestion of lactose
162(1)
Absorption of monosaccharides
163(1)
Digestion and absorption of fat
163(2)
Resynthesis of TAG in intestinal cells
164(1)
Chylomicrons
164(1)
Digestion of other components of food
165(1)
Storage of food components in the body
166(7)
How are the different food components stored in cells?
166(1)
Characteristics of different tissues in terms of energy metabolism
167(2)
Overall control of fuel distribution in the body by hormones
169(1)
Postprandial condition
169(1)
Fasting condition
169(1)
Prolonged fasting and starvation
170(1)
The emergency situation - fight or flight
170(1)
Summary
170(1)
Further reading
171(1)
Problems
171(2)
Chapter 11 Mechanisms of transport, storage, and mobilization of dietary components
173(18)
Glucose traffic in the body
173(7)
Mechanism of glycogen synthesis
173(2)
Breakdown of glycogen to release glucose into the blood
175(2)
Key issues in the interconversion of glucose and glycogen
177(1)
The liver has glucokinase and the other tissues, hexokinase
177(2)
What happens to other sugars absorbed from the intestine?
179(1)
Amino acid traffic in the body (in terms of fuel logistics)
180(1)
Fat and cholesterol movement in the body: an overview
181(1)
Utilization of cholesterol in the body
181(1)
Fat and cholesterol traffic in the body: lipoproteins
182(9)
Apolipoproteins
182(1)
Lipoproteins involved in fat and cholesterol movement in the body
183(1)
Metabolism of chylomicrons
183(1)
Metabolism of VLDL: TAG and cholesterol transport from the liver
183(5)
Release of FFA from adipose cells
188(1)
How are FFA carried in the blood?
188(1)
Summary
189(1)
Further reading
189(1)
Problems
190(1)
Chapter 12 Principles of energy release from food
191(11)
Overview of glucose metabolism
191(2)
Biological oxidation and hydrogen-transfer systems
191(2)
Energy release from glucose
193(4)
The main stages of glucose oxidation
193(1)
Stage 1 in the release of energy from glucose: glycolysis
193(1)
Stage 2 of glucose oxidation: the TCA cycle
194(2)
Stage 3 of glucose oxidation: electron transport to oxygen
196(1)
The electron transport chain - a hierarchy of electron carriers
196(1)
Energy release from oxidation of fat
197(2)
Energy release from oxidation of amino acids
199(1)
The interconvertibility of fuels
199(3)
Summary
200(1)
Problems
201(1)
Chapter 13 Glycolysis, the TCA cycle, and the electron transport system
202(28)
Stage 1 glycolysis
202(5)
Glucose or glycogen?
202(1)
ATP is needed at the beginning of glycolysis
202(3)
Interconversion of dihydroxyacetone phosphate and glyceraldehyde-3-phosphate
205(1)
Glyceraldehyde-3-phosphate dehydrogenase - an oxidation linked to ATP synthesis
205(1)
The final steps in glycolysis
206(1)
Anaerobic glycolysis
207(1)
The ATP balance sheet from glycolysis
207(1)
Transport of pyruvate into the mitochondria
207(1)
Conversion of pyruvate to acetyl-CoA - a preliminary step before the TCA cycle
207(2)
Components involved in the pyruvate dehydrogenase reaction
209(1)
Stage 2 the TCA cycle
209(6)
A simplified version of the TCA cycle
210(1)
Mechanisms of the TCA cycle reactions
210(2)
Generation of GTP coupled to splitting of succinyl-CoA
212(1)
What determines the direction of the TCA cycle?
213(1)
Stoichiometry of the cycle
214(1)
How is the concentration of TCA cycle intermediates maintained?
214(1)
Stage 3 the electron transport chain that conveys electrons from NADH and FADH2 to oxygen
215(15)
The electron transport chain
215(2)
Oxidative phosphorylation - the generation of ATP coupled to electron transport
217(2)
How are protons ejected?
219(1)
ATP synthesis by ATP synthase is driven by the proton gradient
220(1)
Structure of ATP synthase
221(1)
The F1 unit and its role in the conversion of ADP+Pi to ATP
221(1)
Structure of the F0 unit and its role
222(1)
Mechanism by which proton flow causes rotation of F0
223(2)
Transport of ADP into mitochondria and ATP out
225(1)
Reoxidation of cytosolic NADH from glycolysis by electron shuttle systems
225(1)
The balance sheet of ATP production by electron transport
226(1)
Yield of ATP from the oxidation of a molecule of glucose to CO2 and H2O
227(1)
Is ATP production the only use that is made of the potential energy in the proton-motive force?
227(1)
Summary
228(1)
Further reading
229(1)
Problems
229(1)
Chapter 14 Energy release from fat
230(7)
Mechanism of acetyl-CoA formation from fatty acids
230(3)
`Activation' of fatty acids by formation of fatty acyl-CoA derivatives
230(1)
Transport of fatty acyl-CoA derivatives into mitochondria
231(1)
Conversion of fatty acyl-CoA into acetyl-CoA molecules inside the mitochondrion by β-oxidation
232(1)
Energy yield from fatty acid oxidation
232(1)
Oxidation of unsaturated fat
233(1)
Oxidation of odd-numbered carbon-chain fatty acids
233(1)
Ketogenesis in starvation and type 1 diabetes mellitis
234(3)
How is acetoacetate made from acetyl-CoA?
234(1)
Peroxisomal oxidation of fatty acids
235(1)
Where to now?
235(1)
Summary
235(1)
Further reading
236(1)
Problems
236(1)
Chapter 15 An alternative pathway of glucose oxidation. The pentose phosphate pathway
237(6)
The pentose phosphate pathway has two main parts
237(6)
The oxidative part produces equal amounts of ribose-5-phosphate and NADPH
238(1)
Conversion of surplus ribose-5-phosphate into glucose-6-phosphate
238(2)
Conversion of glucose-6-phosphate into ribose-5-phosphate without NADPH generation
240(1)
Generation of NADPH without net production of ribose-5-phosphate
240(1)
Why is the pentose phosphate pathway so important in the erythrocyte?
240(1)
Summary
241(1)
Further reading
242(1)
Problems
242(1)
Chapter 16 Synthesis of glucose (gluconeogenesis)
243(8)
Mechanism of glucose synthesis from pyruvate
243(1)
What are the sources of pyruvate or oxaloacetate used by the liver for gluconeogenesis?
244(2)
Synthesis of glucose from glycerol
246(1)
Synthesis of glucose from propionate
247(1)
Effects of ethanol metabolism on gluconeogenesis
247(1)
Synthesis of glucose via the glyoxylate cycle in bacteria and plants
248(1)
Summary
249(1)
Further reading
250(1)
Problems
250(1)
Chapter 17 Synthesis of fat and related compounds
251(14)
Mechanism of fat synthesis
251(5)
General principles of the process
251(1)
Synthesis of malonyl-CoA is the first step
251(1)
The acyl carrier protein (ACP) and the β-ketoacyl synthase
252(1)
Mechanism of fatty acyl-CoA synthesis
252(1)
Organization of the process of fatty acid synthesis
252(2)
The reductive steps in fatty acid synthesis
254(1)
Fatty acid synthesis takes place in the cytosol
254(2)
Synthesis of unsaturated fatty acids
256(1)
Synthesis of TAG and membrane lipids from fatty acids
256(1)
Synthesis of new membrane lipid bilayer
257(2)
Synthesis of glycerophospholipids
257(2)
Synthesis of new membrane lipid bilayer
259(1)
Synthesis of prostaglandins and related compounds
259(6)
The prostaglandins and thromboxanes
261(1)
Leukotrienes
262(1)
Synthesis of cholesterol
262(1)
Conversion of cholesterol into steroid hormones
262(1)
Summary
263(1)
Further reading
263(1)
Problems
263(2)
Chapter 18 Nitrogen metabolism: amino acid metabolism
265(16)
Nitrogen balance of the body
266(1)
General metabolism of amino acids
266(3)
Aspects of amino acid metabolism
266(1)
Glutamate dehydrogenase has a central role in the deamination of amino acids
267(2)
What happens to the amino group after deamination? The urea cycle
269(6)
Mechanism of arginine synthesis
270(1)
Conversion of citrulline to arginine
270(1)
Transport of the amino nitrogen from extrahepatic tissues to the liver
271(1)
Diseases due to urea cycle deficiencies
272(1)
Alternatives to urea formation exist in different animals
272(1)
Fate of the oxo-acid or carbon skeletons of deaminated amino acids
273(1)
Genetic errors in amino acid metabolism cause diseases
273(1)
Methionine and transfer of methyl groups
274(1)
Synthesis of amino acids
275(1)
Synthesis of glutamate
275(1)
Synthesis of aspartic acid and alanine
275(1)
Synthesis of serine
275(1)
Synthesis of glycine
275(1)
Haem and its synthesis from glycine
275(6)
Destruction of haem
276(1)
Synthesis of adrenaline and noradrenaline
277(2)
Summary
279(1)
Further reading
280(1)
Problems
280(1)
Chapter 19 Nitrogen metabolism: nucleotide metabolism
281(13)
Structure and nomenclature of nucleotides
281(2)
The sugar component of nucleotides
281(1)
The base component of nucleotides
282(1)
Attachment of the bases in nucleotides
282(1)
Synthesis of purine and pyrimidine nucleotides
283(7)
Purine nucleotides
283(4)
The purine salvage pathway
287(1)
Formation of uric acid from purines
287(1)
Control of purine nucleotide synthesis
288(1)
Synthesis of pyrimidine nucleotides
288(1)
How are deoxyribonucleotides formed?
289(1)
Medical effects of folate deficiencies
290(4)
Thymidylate synthesis is targeted by anticancer agents such as methotrexate
290(2)
Summary
292(1)
Further reading
293(1)
Problems
293(1)
Chapter 20 Mechanisms of metabolic control and their applications to metabolic integration
294(28)
Why are controls necessary?
294(1)
The potential clanger of futile cycles in metabolism
294(1)
How are enzyme activities controlled?
295(1)
Metabolic control by varying the amounts of enzymes is relatively slow
295(1)
Metabolic control by regulation of the activities of enzymes in the cell can be very rapid
296(1)
Which enzymes in metabolic pathways are regulated?
296(1)
The nature of control enzymes
296(1)
Allosteric control of enzymes
296(1)
The mechanism of allosteric control of enzymes and its reversibility
297(1)
Allosteric control is a tremendously powerful metabolic concept
297(1)
Control of enzyme activity by phosphorylation
297(1)
Protein kinases and phosphatases are key players in control mechanisms
297(1)
Control by phosphorylation usually depends on chemical signals from other cells
298(1)
General aspects of the hormonal control of metabolism
298(2)
How do glucagon, adrenaline, and insulin work?
298(1)
What is a second messenger?
299(1)
The intracellular second messenger for glucagon and adrenaline is cyclic AMP
299(1)
Control of carbohydrate metabolism
300(1)
Control of glucose uptake into cells
300(1)
Control of glycogen metabolism
301(9)
Control of glycogen breakdown in muscle
302(1)
Mechanism of muscle phosphorylase activation by cAMP
303(1)
Control of glycogen breakdown in the liver
304(1)
Reversal of phosphorylase activation in muscle and liver
304(1)
The switchover from glycogen degradation to glycogen synthesis
304(1)
Mechanism of insulin activation of glycogen synthase
304(1)
Control of glycolysis and gluconeogenesis
305(2)
Muscle and liver PFK2 enzymes are different
307(1)
Fructose metabolism and its control differs from that of glucose
308(1)
Control of pyruvate dehydrogenase, the TCA cycle, and oxidative phosphorylation
309(1)
Controls of fatty acid oxidation and synthesis
310(1)
Nonhormonal controls
310(1)
Degradation of acetyl-CoA carboxylase is another type of control of fat metabolism
310(1)
Hormonal controls on fat metabolism
310(1)
Responses to metabolic stress
311(2)
Response to low ATP concentrations by AMP-activated protein kinase
311(1)
Response of cells to oxygen deprivation
312(1)
Mechanism of the response to hypoxia
312(1)
Integration of metabolism: the fed and fasting state, and diabetes mellitus
313(9)
Metabolism in the fed state
313(1)
Metabolism in the fasting state
314(1)
Metabolism in prolonged starvation
315(1)
Metabolism in type 1 diabetes mellitus
316(2)
Summary
318(2)
Further reading
320(1)
Problems
321(1)
Chapter 21 Raising electrons of water back up the energy scale -- photosynthesis
322(13)
Overview
322(1)
Site of photosynthesis-the chloroplast
322(1)
The light-dependent reactions of photosynthesis
323(4)
The photosynthetic apparatus and its organization in the thylakoid membrane
323(1)
How is light energy captured?
324(1)
Mechanism of light-dependent reduction of NADP+
325(1)
Photosystem II
325(1)
Photosystem I
326(1)
How is ATP generated?
326(1)
The `dark reactions' of photosynthesis -- the Calvin cycle
327(8)
How is CO2 converted into carbohydrate?
327(1)
Rubisco has an apparent efficiency problem
328(1)
The C4 pathway
329(1)
Summary
330(1)
Further reading
331(1)
Problems
331(4)
Part 4 Information storage and utilization
Chapter 22 The genome
335(17)
A brief overview
335(1)
The structures of DNA and RNA
335(1)
DNA is chemically a very simple molecule
335(1)
DNA and RNA are both nucleic acids
336(1)
The primary structure of DNA
336(2)
There are four different nucleotide bases in DNA
336(1)
Attachment of the bases to deoxyribose
336(1)
The physical properties of the polynucleotide components
337(1)
Structure of the polynucleotide of DNA
337(1)
Deoxyribose makes DNA more stable than RNA
338(1)
Thymine instead of uracil allows DNA repair
338(1)
The DNA double helix
338(5)
Complementary base pairing
339(3)
DNA chains are antiparallel; what does this mean?
342(1)
Base pairing in RNA
343(1)
Genome organization
343(1)
The prokaryotic genome
343(1)
Plasmids
343(1)
The eukaryotic genome: chromosomes
343(1)
The mitochondrial genome
344(1)
The structure of protein-coding genes
344(1)
What is a gene?
344(1)
Protein-coding regions of genes in eukaryotes are split up into different sections
344(1)
Gene duplication facilitates evolution of new genes
345(1)
Most of the human genome does not encode proteins
345(2)
Mobile genetic elements: transposons and retroviruses
346(1)
Repetitive DNA sequences
346(1)
RNA-coding genes
347(1)
Pseudogenes
347(1)
Genome packaging
347(5)
The prokaryotic genome is compacted in the cell
347(1)
How is eukaryotic DNA packed into a nucleus?
347(1)
The tightness of DNA packaging changes during the cell cycle
348(1)
The tightness of DNA packing can regulate gene activity
349(1)
Summary
349(1)
Further reading
350(1)
Problems
350(2)
Chapter 23 DNA synthesis, repair, and recombination
352(23)
Overall principle of DNA replication
352(1)
Control of initiation of DNA replication in E. coli
353(1)
Initiation and regulation of DNA replication in eukaryotes
353(1)
Unwinding the DNA double helix and supercoiling
353(3)
How are positive supercoils removed ahead of the replication fork?
354(2)
The basic enzymic reaction catalysed by DNA polymerases
356(1)
How does a new strand get started?
357(1)
The polarity problem in DNA replication
357(1)
Mechanism of Okazaki fragment synthesis
358(3)
Enzyme complex at the replication fork in E. coli
358(2)
Processing the Okazaki fragments
360(1)
The machinery in the eukaryotic replication fork
361(1)
Telomeres solve the problem of replicating the ends of eukaryotic chromosomes
361(2)
How is telomeric DNA synthesized?
362(1)
Telomeres stabilize the ends of linear chromosomes
363(1)
Telomere shortening correlates with ageing
363(1)
How is fidelity achieved in DNA replication?
363(2)
Exonucleolytic proofreading
364(1)
Methyl-directed mismatch repair
364(1)
Repair of DNA damage in E. coil
365(2)
DNA damage repair in eukaryotes
367(1)
Homologous recombination
367(3)
Mechanism of homologous recombination
369(1)
Recombination in eukaryotes
369(1)
Replication of mitochondrial DNA
370(1)
DNA synthesis by reverse transcription in retroviruses
371(4)
Summary
372(1)
Further reading
373(1)
Problems
373(2)
Chapter 24 Gene transcription
375(12)
Messenger RNA
375(2)
The structure of RNA
375(1)
How is mRNA synthesized?
375(1)
Some general properties of mRNA
376(1)
Some essential terminology
377(1)
Gene transcription in E. coli
377(2)
Phases of gene transcription
377(2)
The rate of gene transcription initiation in prokaryotes
379(1)
Control of transcription by different sigma factors
379(1)
Gene transcription in eukaryotic cells
379(4)
Eukaryotic RNA polymerases
379(1)
How is transcription initiated at eukaryotic promoters?
380(1)
Type II eukaryotic gene promoters
380(1)
Elongation of the transcript requires Pol II modification
381(1)
Capping the RNA transcribed by RNA polymerase II
381(1)
Split genes and RNA splicing
382(1)
Ribozymes and self-splicing of RNA
383(2)
Termination of transcription in eukaryotic cells: 3'polyadenylation
384(1)
Editing of mRNAs
384(1)
Transcription of nonprotein-coding genes
385(1)
Gene transcription in mitochondria
385(2)
Summary
385(1)
Further reading
386(1)
Problems
386(1)
Chapter 25 Protein synthesis and controlled protein breakdown
387(23)
Essential basis of the process of protein synthesis
387(1)
The genetic code
388(1)
A preliminary simplified look at the chemistry of peptide synthesis
388(5)
ATP and GTP hydrolysis in translation
389(1)
How are the codons translated?
390(1)
Transfer RNA
390(1)
The wobble mechanism
390(2)
How are amino acids attached to tRNA molecules?
392(1)
Ribosomes
393(1)
Initiation of translation
394(2)
Initiation of translation in E. coli
394(2)
Initiation factors in E. coli
396(1)
Once initiation is achieved, elongation is the next step
396(2)
Elongation factors in E. coli
396(1)
Mechanism of elongation in E. coli
396(2)
How is accuracy of translation achieved?
398(1)
Mechanism of translocation on the E. coli ribosome
398(1)
Termination of protein synthesis in E. coli
399(1)
Physical structure of the ribosome
399(1)
What is a polysome?
400(1)
Protein synthesis in eukaryotes
400(2)
Incorporation of selenocysteine into proteins
402(1)
Protein synthesis in mitochondria
402(1)
Folding up of the polypeptide chain
402(1)
Chaperones (heat shock proteins)
403(1)
Mechanism of action of molecular chaperones
403(2)
Enzymes involved in protein folding
404(1)
Protein folding and prion diseases
405(1)
Programmed destruction of protein by proteasomes
405(5)
Introduction
405(1)
The structure of proteasomes
406(1)
Proteins destined for destruction in proteasomes are marked by ubiquitination
406(1)
The role of proteasomes in the immune system
407(1)
Summary
407(1)
Further reading
408(1)
Problems
409(1)
Chapter 26 Control of gene expression
410(23)
Levels of regulation
410(1)
Gene control in E. coli: the lac operon
410(1)
Structure of the E. coli lac operon
411(1)
Transcriptional regulation in eukaryotes
412(2)
A general overview of the differences in the initiation and control of gene transcription in prokaryotes and eukaryotes
412(1)
DNA elements involved in eukaryotic gene control
413(1)
DNA binding by transcription factors
414(7)
Most transcription factors themselves are regulated
418(1)
Transcription repressors
418(3)
DNA methylation and epigenetic control
421(1)
Gene control after transcription is initiated: an overview
422(1)
Gene control post-transcription initiation in prokaryotes
422(2)
Attenuation in the E. coli trp operon
422(1)
Bacterial riboswitches
423(1)
mRNA stability and the control of gene expression
424(1)
Determinants of eukaryotic mRNA stability and their role in gene expression control
424(1)
Translational control mechanisms in eukaryotes
425(2)
Translational control in iron homeostasis and haem synthesis
426(1)
Regulation of globin synthesis
426(1)
Small RNAs and RNA interference
427(6)
Classes and production of small RNAs in eukaryotes
427(1)
Molecular mechanism of gene silencing by RNAi
427(1)
In vivo functions and importance of noncoding RNA
428(2)
The potential medical and practical importance of RNAi
430(1)
Summary
430(1)
Further reading
431(1)
Problems
431(2)
Chapter 27 Protein sorting and delivery
433(17)
A preliminary overview of the field
433(2)
Structure and function of the ER and Golgi apparatus
434(1)
The importance of the GTP/GDP switch mechanism in protein targeting
435(1)
Translocation of proteins through the ER membrane
436(4)
Synthesis of integral membrane proteins
437(1)
Folding of the polypeptides inside the ER
438(1)
Glycosylation of proteins in the ER lumen and Golgi apparatus
439(1)
Proteins for lysosomes
439(1)
Proteins to be returned to the ER
439(1)
Proteins to be secreted from the cell
439(1)
Proteins are sorted, packaged, and despatched from the ER and Golgi by vesicular transport
440(1)
Mechanism of COP-coated vesicle formation
440(1)
How does a vesicle find its target membrane?
440(1)
Clathrin-coated vesicles transport enzymes from the Golgi to form lysosomes
441(1)
Posttranslational transport of proteins into organelles
441(3)
Transport of proteins into mitochondria
441(1)
Mitochondrial matrix proteins are synthesized as preproteins
441(2)
Delivery of proteins to mitochondrial membranes and intermembrane space
443(1)
Nuclear-cytosolic traffic
444(1)
Why is there a nuclear membrane?
444(1)
The nuclear pore complex
444(2)
Nuclear localization signals
446(4)
GTP/GDP exchange imparts directionality to nuclear-cytosolic transport
446(1)
Regulation of nuclear transport by cell signals and its role in gene control
447(1)
Summary
448(1)
Further reading
449(1)
Problems
449(1)
Chapter 28 Manipulating DNA and genes
450(27)
Basic methodologies
450(4)
Some preliminary considerations
450(1)
Cutting DNA with restriction endonucleases
451(1)
Separating DNA pieces
451(1)
Visualizing the separated pieces
452(1)
Detection of specific DNA fragments by nucleic acid hybridization probes
452(1)
Southern blotting
453(1)
Chemical synthesis of DNA
454(1)
Sequencing DNA
454(2)
The principle of DNA sequencing by the chain-termination method
454(2)
Amplification of DNA by the polymerase chain reaction
456(2)
Analysis of multiple gene expression in cells using DNA microarrays
457(1)
joining DNA to form recombinant molecules
458(1)
Cloning DNA
459(3)
Cloning in plasmids
459(2)
Cloning libraries
461(1)
Cloning vectors for larger pieces of DNA
462(1)
Applications of recombinant DNA technology
462(9)
Working with RNA and cDNA
462(1)
Production of human proteins and proteins from other sources
463(1)
Expressing the cDNA in E. coli
463(1)
Site-directed mutagenesis
464(1)
PCR in forensic science
464(2)
Locating disease-producing genes
466(1)
Knockout mice
467(1)
The embryonic stem (ES) cell system
467(1)
Gene targeting
468(2)
Stem cells and potential therapy for human diseases
470(1)
Gene therapy
470(1)
Transgenic organisms
471(1)
DNA databases and genomics
471(6)
Summary
472(1)
Further reading
472(1)
Problems
473(4)
Part 5 Cells and tissues
Chapter 29 Cell signalling
477(30)
Overview
477(2)
Organization of this chapter
479(1)
What are the signalling molecules?
479(2)
Neurotransmitters
479(1)
Hormones
479(1)
Cytokines and growth factors
480(1)
Vitamin D and retinoic acid
481(1)
Responses mediated by intracellular receptors
481(1)
Responses mediated by receptors in the cell membrane
482(3)
There are three main types of membrane-bound receptors
482(3)
General concepts in cell signalling mechanisms
485(1)
Protein phosphorylation
485(1)
Binding domains of signal transduction proteins
485(1)
Terminating signals
486(1)
Examples of signal transduction pathways
486(1)
Signal transduction pathways from tyrosine kinase receptors
486(9)
The Ras pathway
486(4)
Signal sorting
490(1)
The phosphatidylinositide 3-kinase (PI 3-kinase) pathway and insulin signalling
491(3)
The JAK/STAT pathways: another type of tyrosine kinase-associated signalling system
494(1)
G-protein-coupled receptors and associated signal transduction pathways
495(8)
Overview
495(1)
cAMP as second messenger: adrenaline signalling -- a G-protein pathway
496(3)
The phosphatidylinositol cascade: another example of a G-protein-coupled receptor that works via a different second messenger
499(1)
Other roles of calcium in regulation of cellular processes
500(1)
Vision: a process dependent on a G-protein-coupled receptor
501(2)
Signal transduction pathway using cGMP as a second messenger
503(4)
Membrane receptor-mediated pathways
503(1)
Nitric oxide signalling -- activation of a soluble cytoplasmic guanylate cyclase
503(2)
Summary
505(1)
Further reading
506(1)
Problems
506(1)
Chapter 30 The cell cycle, cell division and cell death
507(11)
The eukaryotic cell cycle
507(1)
The cell cycle is divided into separate phases
507(1)
The cell cycle phases are tightly controlled
507(1)
Cell cycle controls
508(1)
Cytokines and growth factor control in the cell cycle
508(1)
Cell cycle checkpoints
508(1)
Cell cycle controls depend on the synthesis and destruction of cyclins
508(1)
Controls in G1 are complex
509(1)
The G1 checkpoint
510(1)
How is DNA damage detected?
510(1)
Progression to S phase
510(1)
Progression to M phase
510(1)
M phase
510(1)
Cell division
511(2)
Mitosis
511(1)
Meiosis
511(2)
Apoptosis
513(1)
What is the function of apoptosis?
513(1)
There are two main pathways that initiate apoptosis
514(4)
Caspase enzymes are the effectors of apoptosis
514(1)
Mechanism of an intrinsic pathway of apoptosis
515(1)
Regulation of the intrinsic pathway of apoptosis by Bcl-2 proteins
515(1)
Mechanism of the extrinsic pathway of apoptosis
516(1)
Summary
516(1)
Further reading
517(1)
Problems
517(1)
Chapter 31 Cancer
518(9)
General concepts
518(1)
Cancer development involves a progression of mutations
519(1)
Development of colorectal cancer
519(1)
Mutations cause cancer
519(1)
The types of genetic change involved in cancer
520(1)
Oncogenes
521(1)
How are oncogenes acquired?
521(1)
Retroviruses can activate or acquire cellular protooncogenes
522(1)
Tumour-suppressor genes
522(1)
Mechanism of protection by the p53 gene
523(1)
Mechanism of protection by the retinoblastoma gene
523(1)
Molecular biology advances have potential for development of new cancer therapies
523(4)
Summary
524(1)
Further reading
524(1)
Problems
524(3)
Part 6 Protective mechanisms against disease
Chapter 32 Special topics: blood clotting, xenobiotic metabolism, reactive oxygen species
527(9)
Blood clotting (thrombus formation)
527(3)
What signals the necessity for clot formation?
528(1)
How does thrombin cause thrombus formation?
528(1)
Keeping clotting in check
528(1)
Rat poison, blood clotting, and vitamin K
529(1)
Protection against ingested foreign chemicals (xenobiotics)
530(2)
Cytochrome P450
530(1)
Secondary modification -- addition of a polar group to products of the P450 attack
531(1)
Medical significance of P450s
531(1)
Multidrug resistance
532(1)
Protection against reactive oxygen species
532(2)
Formation of the superoxide anion and other reactive oxygen species
532(1)
Mopping up oxygen free radicals with vitamins C and E
533(1)
Enzymic destruction of superoxide by superoxide dismutase
534(1)
The glutathione peroxidase-glutathione reductase system
534(2)
Summary
534(1)
Further reading
535(1)
Problems
535(1)
Chapter 33 The immune system
536(14)
Overview
536(2)
The innate immune system
536(1)
The adaptive immune response
536(1)
The problem of autoimmune reactions
537(1)
The cells involved in the immune system
537(1)
What does the adaptive immune response achieve?
537(1)
Where is the immune system located?
537(1)
Antibody-based or humoral immunity
538(2)
Structure of antibodies (immunoglobulins)
538(1)
What are the functions of antibodies?
539(1)
There are different classes of antibodies
539(1)
Generation of antibody diversity
539(1)
Activation of B cells to produce antibodies
540(4)
Deletion of potentially self-reacting B cells in the bone marrow
541(1)
The theory of clonal selection
541(1)
B cells must be activated before they can develop into antibody-secreting cells
542(1)
Affinity maturation of antibodies
543(1)
Memory cells
544(1)
Cell-mediated immunity (cytotoxic T cells)
544(2)
Mechanism of action of cytotoxic T cells
545(1)
The role of the major histocompatibility complexes (MHCs) in the displaying of peptides on the cell surface
545(1)
CD proteins reinforce the selectivity of T cell receptors for the two classes of MHCs
546(1)
Why does the human immune system reject transplanted human cells?
546(1)
Monoclonal antibodies
546(4)
Humanized monoclonal antibodies
547(1)
Summary
548(1)
Further reading
549(1)
Problems
549(1)
Answers to problems 550(27)
Index of diseases and medically relevant topics 577(1)
Index 578
Dr Despo Papachristodoulou is Senior Lecturer in Biochemistry and also Head of Preclinical Medicine at King's College London. Her research interests include diabetes and diabetic complications, insulin metabolism, intermediary metabolism, nutrition, medical education, and curriculum development.

Dr Alison Snape is Programme Director for the BSc in Biomedical Science and also Senior Lecturer in Biochemistry at King's College London. Her research interests include gene expression and differentiation in early embryonic development. Dr Snape has extensive experience of teaching biochemistry and molecular biology to undergraduates and organises modules for first year students of their BSc Biosciences programmes.