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E-raamat: Biochemistry and Molecular Biology

(Depa), (Reader in Biochemistry and Medical Education, King's College London), (Senior Lecturer and Head of the Teaching Department of Biochemistry, King's College London), (Department of Biochemistry, University of Adelaide, Australia)
  • Formaat: 609 pages
  • Ilmumisaeg: 06-Jul-2018
  • Kirjastus: Oxford University Press
  • Keel: eng
  • ISBN-13: 9780192557940
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  • Formaat: 609 pages
  • Ilmumisaeg: 06-Jul-2018
  • Kirjastus: Oxford University Press
  • Keel: eng
  • ISBN-13: 9780192557940
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Now in its sixth edition, Biochemistry and Molecular Biology provides the perfect balance between detail and conceptual understanding. Maintaining the much-praised clarity of previous editions, this edition incorporates both new techniques and pivotal discoveries in a succinct, easy-to-digest way, using updated figures and diagrams to help explain complex processes.

Updated content on the manipulation of DNA and genes reflects the rapid introduction of new methods in contemporary research, and incorporates up-to-date discussions of recent developments such as gene editing. Chapter summaries are logically laid out, forming bulleted lists which provide students with a consolidation of difficult concepts and progressively guide them through the specifics whilst keeping the big picture in mind. Additional 'find out more' sections provide helpful problem-solving support and the further reading is divided into types to cater for broader learning needs.

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

Online Resources: The online resources to accompany this text include:

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

For students: · Further reading organised by chapter · An extensive bank of multiple-choice questions to support self-directed learning · Links to 3D molecular structures in Protein Data Bank

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 * Good entry level biochemistry textbook that gives students an overview of the diversity of biochemistry and that introduces abstract concepts in a well-explained and accessible way. * Dirk Wildeboer, Natural Sciences, Middlesex University * This textbook presents classical biochemistry material with a balanced emphasis on details and conceptual understanding. Explanations are given in a conversational manner so that students are not distracted by an over-whelming amount of new terminology. * Amanda Storm, Biology, James Madison University *

Acknowledgements vii
About the authors vii
Preface viii
Learning from this book x
Online resources xii
Diseases and medically relevant topics xxvii
Abbreviations xxviii
Part 1 Basic Concepts of life
Chapter 1 The basic molecular themes of life
3(21)
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)
Some basic chemical concepts relevant to biology
5(2)
Chemical bonding in biological molecules
5(1)
Covalent bonds are formed by atoms sharing pairs of electrons
6(1)
Double and single bonds
7(4)
Electronegativity differences cause some covalent bonds to be polar
9(1)
Ions are formed when atoms completely gain or lose electrons
10(1)
Some polar groups can ionize in water
10(1)
Noncovalent bonds are electrostatic interactions
10(1)
Ionic bonds
10(1)
Hydrogen bonds
10(1)
van derWaals interactions
11(1)
Hydrophobic interactions
11(1)
Functional groups determine the characteristic reactions of biological molecules
11(1)
Types of molecules found in living cells
12(2)
Small molecules
12(1)
Macromoleculesare made by polymerization of smaller units
13(1)
Protein and nucleic acid molecules have information content
13(1)
Proteins
14(1)
Catalysis of reactions by enzyme proteins is central to the existence of life
14(1)
What is the function of enzymes?
15(1)
Proteins work by molecular recognition
15(1)
Life is self-assembling due to molecular recognition by proteins
15(1)
Many proteins are molecular machines
15(1)
How can one class of molecule carry out so many tasks?
15(1)
Evolution of proteins
15(1)
Development of new genes
16(1)
DNA (deoxyribonucleic acid)
16(2)
DNA directs its own replication
16(1)
Genetic code
16(2)
Organization of the genome
18(1)
How did life start?
18(1)
The RNA world
18(1)
Proteomics and genomics
19(1)
Appendix: Buffers and pKa values
19(2)
pKa values and their relationship to buffers
20(1)
Summary
21(1)
Further reading
22(1)
Problems
23(1)
Chapter 2 Cells and viruses
24(12)
Cells are the units of all living systems
24(1)
What determines the size of cells?
24(1)
Classification of organisms
24(7)
Prokaryotic cells
25(1)
Eukaryotic cells
26(3)
Basic types of eukaryotic cells
29(2)
Viruses
31(3)
Genetic material of viruses
31(1)
Some examples of viruses of special interest
32(2)
Summary
34(1)
Further reading
35(1)
Problems
35(1)
Chapter 3 Energy considerations in biochemistry
36
Energy considerations
36(4)
Energy considerations determine whether a chemical reaction is possible in the cell
36(2)
Reversible and irreversible reactions and δG values
38(1)
The importance of irreversible reactions in the strategy of metabolism
38(1)
What is the significance of irreversible reactions in a metabolic pathway?
38(1)
How are AG values obtained?
39(1)
Standard free energy values and equilibrium constants
39(1)
The release and utilization of free energy from food
40(1)
ATP is the universal energy intermediate in all life
40(5)
High- and low-energy phosphates
40(1)
What are the structural features of high-energy phosphate compounds?
41(1)
The structure of ATP
42(1)
What transports the --- around the cell?
42(1)
How does ATP drive chemical work?
43(2)
How does ATP drive other types of work?
45(1)
High-energy phosphoryl groups are transferred by enzymes known as kinases
45(1)
Energy considerations in covalent and noncovalent bonds
45(2)
Noncovalent bonds are the basis of molecular recognition and self-assembly of life forms
46(1)
Noncovalent bonds are also important in the structures of individual protein molecules and other macromolecules
46(1)
Summary
47(1)
Further reading
47(1)
Problems
48
Part 2 Structure and function of proteins and membranes
Chapter 4 The structure of proteins
51(1)
Structures of the 20 amino acids used in protein synthesis
51(3)
Symbols for amino acids
52(1)
Aliphatic amino acids
52(1)
Aromatic amino acids
52(1)
Ionized hydrophilic amino acids
53(1)
Uncharged polar hydrophilic amino acids
53(1)
Two amino acids with unusual properties
53(1)
The different levels of protein structure---primary, secondary, tertiary, and quaternary
54(7)
Primary structure of proteins
54(2)
Secondary structure of proteins
56(2)
Tertiary structure of proteins
58(3)
Quaternary structure of proteins
61(1)
Protein homologies and evolution
61(1)
Protein domains
62(1)
Domain shuffling
62(1)
Membrane proteins
63(1)
Conjugated proteins and posttranslational modifications of proteins
63(1)
Extracellular matrix proteins (fibrous proteins)
63(6)
Structure of collagens
63(2)
Structure of elastin
65(1)
Structure of proteoglycans
66(2)
Integrins connect the extracellular matrix to the interior of the cell
68(1)
Myoglobin and haemoglobin illustrate how protein structure is related to function
69(6)
Myoglobin
69(1)
Structure of haemoglobin
70(1)
Binding of oxygen to haemoglobin
70(1)
Theoretical models to explain protein allostery
71(1)
Mechanism of the allosteric change in haemoglobin
72(1)
The essential role of 2,3-bisphosphoglycerate (BPG) in haemoglobin function
73(1)
Effect of pH on oxygen binding to haemoglobin
74(1)
Summary
75(1)
Further reading
76(1)
Problems
77(1)
Chapter 5 Methods in protein investigation
78(17)
Purification of proteins
78(5)
Column chromatography
79(2)
SDS polyacrylarnide gel electrophoresis (SDS-PAGE)
81(1)
Nondenaturing polyacrylarnide gel electrophoresis
82(1)
The principles of mass spectrometry
83(2)
Mass spectrometers consist of three principal components
83(1)
Ionization methods for protein and peptide mass spectrometry
84(1)
Types of mass analysers
84(1)
Types of mass spectrometers
84(1)
Applications of mass spectrometry
85(1)
Molecular weight determination of proteins
85(1)
Identification of proteins using mass spectrometry without sequencing
85(1)
Identification of proteins by limited sequencing and database searching
86(1)
Analysis of posttranslational modification of proteins
86(1)
Methods of sequencing protein
86(1)
Classical methods
86(1)
Sequencing by mass spectrometry
86(1)
Sequence prediction of proteins from gene DNA sequences
87(1)
Determination of the three-dimensional structure of proteins
87(2)
X-ray diffraction
87(1)
Nuclear magnetic resonance spectroscopy
87(2)
Homology modelling
89(1)
Proteomics
89(2)
Bioinforrnatics and databases
91(2)
Summary
93(1)
Further reading
93(1)
Problems
94(1)
Chapter 6 Enzymes
95(17)
Enzyme catalysis
95(3)
The nature of enzyme catalysis
96(1)
The induced-fit mechanism of enzyme catalysis
97(1)
Enzyme kinetics
98(4)
Hyperbolic kinetics of a `classical' enzyme
98(2)
Allosteric enzymes
100(2)
General properties of enzymes
102(2)
Nomenclature of enzymes
102(1)
Isozymes
102(1)
Enzyme cofactors and activators
102(1)
Covalent modification of enzymes
103(1)
Effect of pH on enzymes
103(1)
Effect of temperature on enzymes
103(1)
Effect of inhibitors on enzymes
103(1)
Competitive and noncompetitive inhibitors
103(1)
Mechanism of enzyme catalysis
104(5)
Mechanism of the chymotrypsin reaction
105(1)
The catalytic triad of the active site
105(1)
The reactions at the catalytic site of chymotrypsin
106(1)
What is the function of the aspartate residue of the catalytic triad?
107(1)
Otherserine proteases
108(1)
A brief description of other types of protease
109(1)
Summary
109(1)
Further reading
110(1)
Problems
110(2)
Chapter 7 The cell membrane and membrane proteins
112(23)
Basic lipid architecture of membranes
112(7)
The polar lipid constituents of cell membranes
112(2)
What are the polar groups attached to the phosphatidic acid?
114(2)
Membrane lipid nomenclature
116(1)
What is the advantage of having so many different types of membrane lipid?
116(1)
The fatty acid components of membrane lipids
117(1)
What is cholesterol doing In membranes?
117(1)
The self-sealing character of the lipid bilayer
118(1)
Permeability characteristics of the lipid bilayer
118(1)
Membrane proteins and membrane structure
119(1)
Structures of integral membrane proteins
120(2)
Anchoring of peripheral membrane proteins to membranes
121(1)
Glycoproteins
121(1)
Functions of membranes
122(12)
Membrane transport
122(3)
Passive transport or facilitated diffusion
125(1)
Gated ion channels
125(1)
Mechanism of the selectivity of the potassium channel
126(1)
Nerve-impulse transmission
127(2)
How does acetylcholine binding to a membrane receptor result in a nerve impulse?
129(3)
Myelinated neurons permit more rapid nerve-impulse transmission
132(1)
Role of the cell membrane in maintaining the shape of the cell
132(2)
Cell-cell interactions---tight junctions, gap junctions, and cellular adhesive proteins
134(1)
Summary
134(1)
Further reading
135(1)
Problems
135(1)
Chapter 8 Muscle contraction, the cytoskeleton, and molecular motors
135(20)
Muscle contraction
136(1)
A reminder of conformational changes in proteins
136(1)
Types of muscle cell and their energy supply
136(4)
Structure of skeletal striated muscle
137(2)
How does the myosin head convert the energy of ATP hydrolysis into mechanical force on the actin filament?
139(1)
Control of voluntary striated muscle
140(1)
How does Ca2+ trigger contraction?
140(1)
Smooth muscle differs in structure and control from striated muscle
141(2)
Control of smooth muscle contractions
141(2)
The cytoskeleton
143(1)
An overview
143(1)
The cytoskeleton is in a constant dynamic state
144(1)
The role of actin and myosin in nonmuscle cells
144(3)
Assembly and collapse of actin filaments
145(2)
The role of actin and myosin in cell movement
147(1)
The role of actin and myosin in intracellular transport of vesicles
147(1)
Microtubules, cell movement, and intracellular transport
147(3)
Molecular motors: kinesins and dyneins
148(1)
Role of microtubules in cell movement
149(1)
Role of microtubules and molecular motors in mitosis
149(1)
Intermediate filaments
150(1)
Summary
151(1)
Further reading
152(1)
Problems
152(3)
Part 3 Metabolism and nutrition
Chapter 9 General principles of nutrition
155(9)
The requirement for energy and nutrients
155(5)
Protein
156(1)
Fats
156(1)
Carbohydrates
157(1)
Vitamins
157(3)
Guidelines for a healthy diet
160(1)
Regulation of food intake
160(2)
Hunger, appetite, and satiety
161(1)
Integration of hunger and satiety signals by the hypothalamus
161(1)
Summary
162(1)
Further reading
163(1)
Problems
163(1)
Chapter 10 Food digestion, absorption, and distribution to the tissues
164(17)
Chemistry of foodstuffs
164(1)
Digestion and absorption
165(1)
Anatomy of the digestive tract
166(1)
What are the energy considerations in digestion and absorption?
166(1)
A major question in digestion---why doesn't the body digest itself?
166(1)
Digestion of proteins
166(2)
HCI production in the stomach
167(1)
Pepsin, the proteolytic enzyme of the stomach
167(1)
Completion of protein digestion in the small intestine
167(1)
Activation of the pancreatic proenzymes
168(1)
Absorption of amino acids into the bloodstream
168(1)
Digestion of carbohydrates
168(3)
Structure of carbohydrates
168(1)
Digestion of starch
169(1)
Digestion of sucrose
170(1)
Digestion of lactose
170(1)
Absorption of monosaccharides
170(1)
Digestion and absorption of fat
171(2)
Resynthesis of TAG in intestinal cells
172(1)
Chylomicrons
172(1)
Digestion of other components of food
173(1)
Storage of food components in the body
173(6)
Flow are food components stored in cells?
174(1)
Characteristics of different tissues in terms of energy metabolism
175(2)
Overall control of fuel distribution in the body by hormones
177(1)
Postprandial condition/absorptive state
178(1)
Fasting condition
178(1)
Prolonged fasting and starvation
178(1)
The emergency situation----fight or flight
179(1)
Summary
179(1)
Further reading
180(1)
Problems
180(1)
Chapter 11 The storage fuels: mechanisms of transport, storage, and mobilization of carbohydrate and fat
181(18)
Glucose traffic in the body
181(7)
Mechanism of glycogen synthesis
181(3)
Breakdown of glycogen to release glucose into the blood
184(1)
Key issues in the interconversion of glucose and glycogen
185(1)
The liver has glucokinase and the other tissues, hexokinase
185(2)
What happens to other sugars absorbed from the intestine?
187(1)
Amino acid traffic in the body (in terms of fuel logistics)
188(1)
Fat and cholesterol movement in the body: an overview
188(2)
Utilization of cholesterol in the body
189(1)
Fat and cholesterol traffic in the body: lipoproteins
190(7)
Apolipoproteins
190(1)
Lipoproteins involved in fat and cholesterol movement in the body
190(1)
Metabolism of chylomicrons
191(1)
Metabolism of VLDL:TAG and cholesterol transport from the liver
192(4)
Mobilization of fat: release of FFA from adipose cells
196(1)
How are FFA carried in the blood?
196(1)
Summary
197(1)
Further reading
197(1)
Problems
198(1)
Chapter 12 Principles of energy release from food
199(11)
Overview of glucose metabolism
199(2)
Biological oxidation and hydrogen-transfer systems
199(2)
Energy release from glucose
201(4)
The main stages of glucose oxidation
201(1)
Stage 1 In the release of energy from glucose: glycolysis
201(1)
Stage 2 Of glucose oxidation: the TCA cycle
202(2)
Stage 3 Of glucose oxidation: electron transport to oxygen
204(1)
The electron transport chain: a hierarchy of electron carriers
204(1)
Energy release from oxidation of fat
205(2)
Energy release from oxidation of amino acids
207(1)
The interconvertibility of fuels
207(1)
Summary
208(1)
Further reading
209(1)
Problems
209(1)
Chapter 13 Glycolysis, the TCA cycle, and the electron transport system
210(29)
Stage 1 Glycolysis
210(5)
Glucose or glycogen? It depends on the location
210(1)
ATP is needed at the beginning of glycolysis
210(3)
Interconversion of dihydroxyacetone phosphate and glyceraldehyde-3-phosphate
213(1)
Glyceraldehyde-3-phosphate dehydrogenase: an oxidation linked to ATP synthesis
213(1)
The final steps in glycolysis
214(1)
An ae robic glycolysis
215(1)
The ATP balance sheet from glycolysis
215(1)
Transport of pyruvate into the mitochondria
215(1)
Conversion of pyruvate into acetyl-CoA: a preliminary step before theTCA cycle
215(2)
Components involved in the pyruvate dehydrogenase reaction
217(1)
Stage 2 The TCA cycle
217(6)
A simplified version of the TCA cycle
218(1)
Mechanisms of the TCA cycle reactions
218(2)
Generation of GTP coupled to splitting of succinyl-CoA
220(1)
What determines the direction of the TCA cycle?
221(1)
Stoichiometry of the cycle
222(1)
How is the concentration of TCA cycle intermediates maintained?
222(1)
Stage 3 The Electron Transport Chain that conveys electrons from NADH and FADH, to oxygen
223(13)
The electron transport chain
223(2)
Oxidative phosphorylation: the generation of ATP coupled to electron transport
225(2)
How are protons ejected?
227(1)
ATP synthesis by ATP synthase is driven by the proton gradient
228(1)
Structure of ATP synthase
229(1)
The F1 unit and its role in the conversion of ADP + PI to ATP
229(2)
Structure of the F0 unit and its role
231(1)
Mechanism by which proton flow causes rotation of F0
231(2)
Transport of ADP into mitochondria and ATP out
233(1)
Re-oxidation of cytosolic NADH from glycolysis by electron shuttle systems
233(1)
The balance sheet of ATP production by electron transport
234(1)
Yield of ATP from the oxidation of a molecule of glucose to CO2 and H2O
235(1)
Is ATP production the only use that is made of the potential energy in the proton-motive force?
235(1)
Summary
236(1)
Further reading
237(1)
Problems
237(2)
Chapter 14 Energy release from fat
239(7)
Mechanism of acetyl-CoA formation from fatty acids
240(2)
`Activation' of fatty acids by formation of fatty acyl-CoA derivatives
240(1)
Transport of fatty acyl-CoA derivatives into mitochondria
240(1)
Conversion of fatty acyl-CoA into acetyl-CoA molecules inside the mitochondrion by β-oxidation
241(1)
Energy yield from fatty acid oxidation
241(1)
Oxidation of unsaturated fat
242(1)
Oxidation of odd-numbered carbon-chain fatty acids
242(1)
Ketogenesis in starvation and type 1 diabetes mellitus
243(1)
How is acetoacetate made from acetyl-CoA?
243(1)
Peroxisomal oxidation of fatty acids
244(1)
Where to now?
244(1)
Summary
244(1)
Further reading
245(1)
Problems
245(1)
Chapter 15 An alternative pathway of glucose oxidation: the pentose phosphate pathway
246(6)
The pentose phosphate pathway has two main parts
246(5)
The oxidative part produces equal amounts of ribose-5-phosphate and NADPH
247(1)
Conversion of surplus ribose-5-phosphate into glucose-6-phosphate
247(2)
Conversion of glucose-6-phosphate into ribose-5-phosphate without NADPH generation
249(1)
Generation of NADPH without net production of ribose-5-phosphate
249(1)
Why is the pentose phosphate pathway so important in the erythrocyte?
249(2)
Summary
251(1)
Further reading
251(1)
Problems
251(1)
Chapter 16 Synthesis of glucose (gluconeogenics)
252(8)
Mechanism of glucose synthesis from pyruvate
252(6)
What are the sources of pyruvate or oxaloacetate used by the liver for gluconeogenesis?
254(1)
Synthesis of glucose from glycerol
255(1)
Synthesis of glucose from propionate
256(1)
Effects of ethanol metabolism on gluconeogenesis
256(1)
Synthesis of glucose via the glyoxylate cycle in bacteria and plants
257(1)
Summary
258(1)
Further reading
259(1)
Problems
259(1)
Chapter 17 Synthesis of fat and related compounds
260(13)
Mechanism of fat synthesis
260(5)
General principles of the process
260(1)
Synthesis of malonyl-CoA is the first step
260(1)
The acyl carrier protein (ACP) and the β-ketoacyl synthase
261(1)
Mechanism of fatty acyl-CoA synthesis
261(1)
Organization of the process of fatty acid synthesis
261(2)
The reductive steps in fatty acid synthesis
263(1)
Fatty acid synthesis takes place in the cytosol
263(2)
Synthesis of unsaturated fatty acids
265(1)
Synthesis of TAG and membrane lipids from fatty acids
265(1)
Synthesis of new membrane lipid bilayer
266(3)
Synthesis of glycerophospholipids
266(2)
Synthesis of new membrane lipid bilayer
268(1)
Synthesis of prostaglandins and related compounds
269(2)
The prostaglandins and thromboxanes
270(1)
Leukotrienes
270(1)
Synthesis of cholesterol
270(1)
Conversion of cholesterol into steroid hormones
271(1)
Summary
271(1)
Further reading
272(1)
Problems
272(1)
Chapter 18 Nitrogen metabolism: amino acid metabolism
273(16)
Nitrogen balance in the body
274(1)
General metabolism of amino acids
274(3)
Aspects of amino acid metabolism
274(1)
Glutamate dehydrogenase has a central role in the deamination of amino acids
275(2)
What happens to the amino group after deamination? The urea cycle
277(6)
Mechanism of arginine synthesis
278(1)
Conversion of citrulline to arginine
278(1)
Transport of the amino nitrogen from extrahepatic tissues to the liver
279(1)
Diseases due to urea cycle deficiencies
280(1)
Alternatives to urea formation exist in different animals
280(1)
Fate of the oxo-acid or carbon skeletons of deaminated amino acids
280(1)
Genetic errors in amino acid metabolism cause diseases
281(1)
Methionine and transfer of methyl groups
282(1)
Synthesis of amino acids
283(1)
Synthesis of glutamate
283(1)
Synthesis of aspartic acid and alanine
283(1)
Synthesis of serine
283(1)
Synthesis of glycine
283(1)
Haem and its synthesis from glycine
283(4)
Destruction of haem
284(1)
Synthesis of adrenaline and noradrenaline
285(2)
Summary
287(1)
Further reading
288(1)
Problems
288(1)
Chapter 19 Nitrogen metabolism: nucleotide metabolism
289(13)
Structure and nomenclature of nucleotides
289(2)
The sugar component of nucleotides
289(1)
The base component of nucleotides
290(1)
Attachment of the bases in nucleotides
290(1)
Synthesis of purine and pyrimidine nucleotides
291(7)
Purine nucleotides
291(4)
The purine salvage pathway
295(1)
Formation of uric acid from purines
296(1)
Control of purine nucleotide synthesis
296(1)
Synthesis of pyrimidine nucleotides
297(1)
How are deoxyribonucleotides formed?
297(1)
Medical effects of folate deficiencies
298(2)
Thymidylate synthesis is targeted by anticancer agents such as methotrexate
299(1)
Summary
300(1)
Further reading
301(1)
Problems
301(1)
Chapter 20 Mechanisms of metabolic control and their applications to metabolic integration
302(28)
Why are controls necessary?
302(1)
The potential danger of futile cycles in metabolism
302(1)
How are enzyme activities controlled?
303(1)
Metabolic control by varying the quantities of enzymes is relatively slow
303(1)
Metabolic control by regulation of the activities of enzymes in the cell can be very rapid
304(1)
Which enzymes in metabolic pathways are regulated?
304(1)
The nature of control of enzymes
304(1)
Allosteric control of enzymes
304(1)
The mechanism of allosteric control of enzymes and its reversibility
305(1)
Allosteric control is a tremendously powerful metabolic concept
305(1)
Control of enzyme activity by phosphorylation
305(1)
Protein kinases and phosphatases are key players in control mechanisms
305(1)
Control by phosphorylation usually depends on chemical signals from other cells
306(1)
General aspects of the hormonal control of metabolism
306(2)
How do glucagon, adrenaline, and insulin work?
306(1)
What is a second messenger?
307(1)
The intracellular second messenger for glucagon and adrenaline is cyclic AMP
307(1)
Control of carbohydrate metabolism
308(2)
Control of glucose uptake into cells
308(2)
Control of glycogen metabolism
310(8)
Control of glycogen breakdown in muscle
310(1)
Mechanism of muscle phosphorylase activation by cAMP
311(1)
Control of glycogen degradation in the liver
312(1)
Reversal of phosphorylase activation in muscle and liver
312(1)
The switchover from glycogen degradation to glycogen synthesis
312(1)
Mechanism of insulin activation of glycogen synthase
313(1)
Control of glycolysis and gluconeogenesis
314(1)
Muscle and liver PFK2 enzymes are different
315(1)
Fructose metabolism and its control differs from that of glucose
316(1)
Control of pyruvate dehydrogenase, the TCA cycle, and oxidative phosphorylation
317(1)
Controls of fatty acid oxidation and synthesis
318(1)
Nonhormonal controls
318(1)
Degradation of acetyl-CoA carboxylase is another type of control of fat metabolism
318(1)
Hormonal controls on fat metabolism
318(1)
Responses to metabolic stress
319(1)
Response to low ATP concentrations by AMP-activated protein kinase
319(1)
Response of cells to oxygen deprivation
320(1)
Mechanism of the response to hypoxia
320(1)
Integration of metabolism: the fed and fasting state, and diabetes mellitus
320(6)
Metabolism in the fed state
321(1)
Metabolism in the fasting state
322(1)
Metabolism in prolonged starvation
323(1)
Metabolism in type 1 diabetes mellitus
324(2)
Summary
326(3)
Further reading
329(1)
Problems
329(1)
Chapter 21 Raising electrons of water back up the energy scale: photosynthesis
330(13)
Overview
330(1)
Site of photosynthesis: the chloroplast
330(1)
The light-dependent reactions of photosynthesis
331(4)
The photosynthetic apparatus and its organization in the thylakoid membrane
331(1)
How is light energy captured?
332(1)
Mechanism of light-dependent reduction of NADP'
333(1)
Photosystem II
333(1)
Photosystem I
333(1)
How is ATP generated?
334(1)
The `dark reactions' of photosynthesis: the Calvin cycle
335(3)
How is CO2 converted into carbohydrate?
335(1)
Rubisco has an apparent efficiency problem
336(1)
The C4 pathway
337(1)
Summary
338(1)
Further reading
338(1)
Problems
338(5)
Part 4 Information storage and utilization
Chapter 22 The genome
343(17)
A brief overview
313(30)
The structures of DNA and RNA
343(1)
DNA is chemically a very simple molecule
343(1)
DNA and RNA are both nucleic acids
344(1)
The primary structure of DNA
344(3)
There are four different nucleotide bases in DMA
344(1)
Attachment of the bases to deoxyribose
344(1)
The physical properties of the polynucleotide components
345(1)
Structure of the polynucleotide of DNA
345(1)
Deoxyribose makes DNA more stable than RNA
346(1)
Thymine instead of uracil allows DNA repair
346(1)
The DNA double helix
347(4)
Complementary base pairing
347(3)
DNA chains are antiparallel; what does this mean?
350(1)
Base pairing in RNA
350(1)
Genome organization
351(1)
The prokaryotic genome
351(1)
Plasmids
351(1)
The eukaryotic genome: chromosomes
351(1)
The mitochondrial genome
351(1)
The structure of protein-coding genes
352(2)
What is a gene?
352(1)
Protein-coding regions of genes in eukaryotes are split up into different sections
352(1)
Gene duplication facilitates evolution of new genes
353(1)
Most of the human genome does not encode proteins
354(2)
Mobile genetic elements
354(1)
Repetitive DNA sequences
355(1)
RNA-coding genes
355(1)
Pseudogenes
355(1)
Genome packaging
356(2)
The prokaryotic genome is compacted in the cell
356(1)
How is eukaryotic DNA packed into a nucleus?
356(1)
The tightness of DNA packaging changes during the cell cycle
356(1)
The tightness of DNA packing can regulate gene activity
357(1)
Summary
358(1)
Further reading
359(1)
Problems
359(1)
Chapter 23 DNA synthesis, repair, and recombination
360(22)
Overall principle of DNA replication
360(1)
Control of initiation of DNA replication in E coli
361(1)
Initiation and regulation of DNA replication In eukaryotes
361(1)
Unwinding the DMA double helix and supercoiling
361(3)
How are positive supercoils removed ahead of the replication fork?
362(2)
The basic enzymic reaction catalysed by DNA polymerases
364(1)
How does a new strand get started?
365(1)
The polarity problem in DNA replication
365(1)
Mechanism of Okazaki fragment synthesis
366(3)
Enzyme complex at the replication fork in E Kit
366(2)
Processing the Okazaki fragments
368(1)
The machinery in the eukaryotic replication fork
369(1)
Telomeres solve the problem of replicating the ends of eukaryotic chromosomes
369(2)
How is telomeric DNA synthesized?
370(1)
Telomeres stabilize the ends of linear chromosomes
371(1)
Telomere shortening correlates with ageing
371(1)
How is fidelity achieved in DNA replication?
371(2)
Exonucleolytic proofreading
372(1)
Methyl-directed mismatch repair
372(1)
Repair of DNA damage in E. coli
373(2)
DNA damage repair in eukaryotes
375(1)
Homologous recombination
375(4)
Mechanism of homologous recombination
375(4)
Recombination in eukaryotes
379(1)
Replication of mitochondrial DNA
379(1)
DNA synthesis by reverse transcription in retroviruses
379(1)
Summary
380(1)
Further reading
381(1)
Problems
381(1)
Chapter 24 Gene transcription
382(13)
Messenger RNA
382(2)
The structure of RNA
382(1)
How is mRNA synthesized?
382(1)
Some general properties of mRNA
383(1)
Some essential terminology
383(1)
Gene transcription in E. coli
384(2)
Phases of gene transcription
384(2)
The rate of gene transcription initiation in prokaryotes
386(1)
Control of transcription by different sigma factors
386(1)
Gene transcription in eukaryotic cells
386(5)
Eukaryotic RNA polymerases
386(1)
How is transcription initiated at eukaryotic promoters?
387(1)
Type II eukaryotic gene promoters
387(1)
Elongation of the transcript requires Pol II modification
388(1)
Capping the RNA transcribed by RNA polymerase II
388(1)
Split genes and RNA splicing
389(2)
Ribozymes and self-splicing of RNA
391(1)
Termination of transcription in eukaryotic cells: 3' polyadenylation
391(1)
Editing of mRNAs
392(1)
Transcription of nonprotetn-coding genes
392(1)
Gene transcription in mitochondria
393(1)
Summary
393(1)
Further reading
394(1)
Problems
394(1)
Chapter 25 Protein synthesis and controlled protein breakdown
395(23)
Essential basis of the process of protein synthesis
395(1)
The genetic code
396(1)
A preliminary simplified look at the chemistry of peptide synthesis
396(4)
ATP and GTP hydrolysis in translation
397(1)
How are the codons translated?
397(1)
Transfer RNA
398(1)
The wobble mechanism
398(1)
How are amino acids attached to tRNA molecules?
399(1)
Ribosomes
400(2)
Initiation of translation
402(2)
Initiation of translation in E. coli
402(1)
Initiation factors in E. coli
403(1)
Once initiation is achieved, elongation is the next step
404(2)
Elongation factors in E. coli
404(1)
Mechanism of elongation in E. coli
404(1)
How is accuracy of translation achieved?
405(1)
Mechanism of translocation on the E. coli ribosome
406(1)
Termination of protein synthesis in E. coli
407(1)
Physical structure of the ribosome
407(1)
What is a polysome?
408(1)
Protein synthesis in eukaryotes
408(2)
Incorporation of selenocysteine into proteins
410(1)
Protein synthesis in mitochondria
410(1)
Folding up of the polypeptide chain
410(1)
Chaperones (heat shock proteins)
410(1)
Mechanism of action of molecular chaperones
411(1)
Enzymes involved in protein folding
412(1)
Protein folding and prion diseases
412(1)
Programmed destruction of protein by proteasomes
413(2)
Introduction
413(1)
The structure of proteasomes
413(1)
Proteins destined for destruction in proteasomes are marked by ubiquitination
414(1)
The role of proteasomes in the immune system
415(1)
Summary
415(1)
Further reading
416(1)
Problems
416(2)
Chapter 26 Control of gene expression
418(22)
Levels of regulation
418(2)
Gene control in E. coli: the lac operon
418(1)
Structure of the E. coli lac operon
419(1)
Transcriptional regulation in eukaryotes
420(9)
A general overview of the differences in the initiation and control of gene transcription in prokaryotes and eukaryotes
420(1)
DNA elements involved in eukaryotic gene control
421(1)
Transcription factors can be classified by protein motifs that are involved in DNA binding
422(3)
How do eukaryotic transcription factors influence transcription?
425(1)
Most transcription factors are themselves regulated
426(1)
Transcription repressors
426(1)
The role of chromatin in eukaryotic gene control
427(2)
DNA methylation and epigenetic control
429(1)
Gene control after transcription is initiated: an overview
429(1)
Gene control post-transcription initiation in prokaryotes
430(1)
Attenuation in the E. coli trp operon
430(1)
Bacterial riboswitches
430(1)
mRNA stability and the control of gene expression
431(2)
Determinants of eukaryotic mRNA stability and their role in gene expression control
432(1)
Translational control mechanisms in eukaryotes
433(1)
Translational control in iron homeostasis and haem synthesis
433(1)
Regulation of globin synthesis by translation initiation factor elF2
434(1)
Small RNAs and RNA interference
434(4)
Classes and production of small RNAs in eukaryotes
434(2)
Molecular mechanism of gene silencing by RNAi
436(1)
In vivo functions and importance of noncoding RNA
437(1)
The potential medical and practical importance of RNAi
437(1)
Summary
438(1)
Further reading
439(1)
Problems
439(1)
Chapter 27 Protein sorting and delivery
440(17)
A preliminary overview of the field
440(2)
Structure and function of the ER and Golgi apparatus
441(1)
The importance of the GTP/GDP switch mechanism in protein targeting
442(1)
Translocation of proteins through the ER membrane
443(4)
Mechanism of cotranslational transport through the ER membrane
443(2)
Synthesis of integral membrane proteins
445(1)
Folding of the polypeptides inside the ER
445(1)
Glycosylation of proteins in the ER lumen and Golgi apparatus
446(1)
Proteins for lysosomes
446(1)
Proteins to be returned to the ER
446(1)
Proteins to be secreted from the cell
446(1)
Proteins are sorted, packaged, and dispatched from the ER and Golgi by vesicular transport
447(1)
Mechanism of COP-coated vesicle formation
447(1)
How does a vesicle find its target membrane?
447(1)
Clathrin-coated vesicles transport enzymes from the Golgi to form lysosomes
448(1)
Posttranslational transport of proteins into organelles
448(3)
Transport of proteins into mitochondria
448(1)
Mitochondrial matrix proteins are synthesized as preproteins
449(1)
Delivery of proteins to mitochondrial membranes and intermembrane space
450(1)
Nuclear-cytosolic traffic
451(1)
Why is there a nuclear membrane?
451(1)
The nuclear pore complex
451(1)
Nuclear localization signals
452(3)
Importins combine with nuclear localization signals on proteins to be transported into the nucleus
453(1)
GTP/GDP exchange imparts directionality to nuclear-cytosolic transport
453(1)
Regulation of nuclear transport by cell signals and its role in gene control
454(1)
Summary
455(1)
Further reading
456(1)
Problems
456(1)
Chapter 28 Manipulating DMA and genes
457(28)
Basic methodologies
457(4)
Some preliminary considerations
457(1)
Cutting DNA with restriction enclonucleases
458(1)
Separating DNA pieces
458(1)
Visualizing the separated pieces
459(1)
Detection of specific DNA fragments by nucleic acid hybridization probes
459(1)
Southern blotting
460(1)
Chemical synthesis of DNA
460(1)
Sequencing DNA
461(3)
The principle of DNA sequencing by the chain-termination method
461(3)
Amplification of DNA by the polymerase chain reaction
464(2)
Analysis of multiple gene expression in cells using DNA microarrays
465(1)
Joining DNA to form recombinant molecules
466(1)
Cloning DNA
466(4)
Cloning in plasmids
467(1)
Cloning libraries
468(1)
Cloning vectors for larger pieces of DNA
469(1)
Applications of recombinant DNA technology
470(10)
Working with RNA and cDNA to study gene expression
470(1)
Production of human proteins and proteins from other sources
470(1)
Expressing the cDNA in E. coli
471(1)
Site-directed mutagenesis
472(1)
PCR in forensic science
472(1)
Locating disease-producing genes
473(2)
Knockout mice
475(1)
The embryonic stem (ES) cell system
475(1)
Gene targeting
475(1)
Stem cells and potential therapy for human diseases
476(1)
Gene therapy
477(1)
Genome editing using CRISPR
478(1)
Transgenic organisms
478(1)
DNA databases and genomics
479(1)
Summary
480(1)
Further reading
480(1)
Problems
481(4)
Part 5 Cells And Tissuses
Chapter 29 Cell signaling
485(30)
Overview
485(2)
Organization of this chapter
487(1)
What are the signalling molecules?
487(2)
Neurotransmitters
487(1)
Cytokines and growth factors
488(1)
Vitamin D and retinoic acid
489(1)
How do cells detect signals and how do they transmit that information to the interior of the cell?
489(1)
Responses mediated by intracellular receptors
489(1)
Responses mediated by receptors in the cell membrane
490(3)
There are three main types of membrane-bound receptors
490(3)
General concepts in cell signalling mechanisms
493(1)
Protein phosphorylation
493(1)
Binding domains of signal transduction proteins
493(1)
Terminating signals
494(1)
Signalling mechanisms in greater detail
494(1)
Examples of signal transduction pathways
494(1)
Signal transduction pathways from tyrosine kinase receptors
494(10)
The Ras pathway
494(5)
The phosphatidylinositide 3-kinase (PI 3-kinase) pathway and insulin signalling
499(4)
The JAK/STAT pathways: another type of tyrosine kinase-associated signalling system
503(1)
G-protein-coupled receptors and associated signal transduction pathways
504(7)
Overview
504(1)
cAMP as second messenger: adrenaline signalling: a G-protein pathway
504(3)
The phosphatidylinositol cascade: another example of a G-protein-coupled receptor that works via a different second messenger
507(1)
Other roles of calcium in regulation of cellular processes
508(1)
Vision: a process dependent on a G-protein-coupled receptor
509(2)
Signal transduction pathway using cGMP as a second messenger
511(1)
Membrane receptor-mediated pathways
511(1)
Nitric oxide signalling: activation of a soluble cytosolic guanylate cyclase
511(1)
Overview and summary
512(1)
Summary
513(1)
Further reading
514(1)
Problems
514(1)
Chapter 30 The cell cycle, cell division, cell death, and cancer
515(22)
The eukaryotic cell cycle
515(1)
The cell cycle is divided into separate phases
515(1)
The cell cycle phases are tightly controlled
516(1)
Cell cycle controls
516(2)
Cytokines and growth factor control in the cell cycle
516(1)
Cell cycle checkpoints
517(1)
Cell cycle controls depend on the synthesis and destruction of cyclins
517(1)
Controls in G1 are complex
518(1)
The G1 checkpoint
518(1)
How is DNA damage detected?
519(1)
Progression to S phase
519(1)
Progression to M phase
519(1)
M phase
520(1)
Cell division
520(2)
Mitosis
520(1)
Meiosis
521(1)
Apoptosis
522(1)
What is the function of apoptosis?
522(1)
There are two main pathways that initiate apoptosis
523(2)
Caspase enzymes are the effectors of apoptosis
523(1)
The intrinsic pathway of apoptosis involves mitochondria
524(1)
Regulation of the intrinsic pathway of apoptosis by Bcl-2 proteins
524(1)
The extrinsic pathway of apoptosis involves death receptors on the cell surface
525(1)
Cancer
525(1)
Telomere shortening limits the number of times most normal cells can divide
525(1)
Cancer development involves a progression of mutations
526(2)
Development of colorectal cancer
527(1)
Genetic changes in cancer involve oncogenes and tumour-suppressor genes
528(1)
Oncogenes frequently activate signalling pathways
528(2)
How are oncogenes acquired?
529(1)
Retroviruses can activate or acquire cellular Protooncogenes
529(1)
Tumour-suppressor genes are cell cycle control genes
530(1)
Mechanism of protection by the p53 gene
530(1)
Mechanism of protection by the retinoblastoma gene
530(1)
Molecular biology advances have potential for development of new cancer therapies
531(1)
Summary
532(1)
Further reading
533(1)
Problems
533(4)
Part 6 Protective mechanisms against disease
Chapter 31 Blood clotting, xenobiotic metabolism, and reactive oxygen spades
537(10)
Blood clotting (coagulation, thrombus formation)
537(3)
What signals the necessity for clot formation?
538(1)
How does thrombin cause thrombus formation?
538(1)
Keeping clotting in check
539(1)
Rat poison, blood clotting, and vitamin K
539(1)
Protection against ingested foreign chemicals (xenobiotics)
540(2)
Cytochrome P450
540(1)
Secondary modification: addition of a polar group to products of the P450 attack
541(1)
Medical significance of P450s
542(1)
Multidrug resistance
542(1)
Protection against reactive oxygen species (ROS)
542(2)
Formation of the superoxide anion and other reactive oxygen species
542(1)
Mopping up oxygen free radicals with vitamins C and E
543(1)
Enzymatic destruction of superoxide by superoxide dismutase
544(1)
The glutathione peroxidase-glutathione reductase system
544(1)
Summary
545(1)
Further reading
545(1)
Problems
545(2)
Chapter 32 The immune system
547(16)
Overview
547(2)
The innate immune response
547(1)
The adaptive immune response
547(1)
The problem of autoimmune reactions
548(1)
The cells involved in the immune system
548(1)
What does the adaptive immune response achieve?
548(1)
Where is the adaptive immune system located?
548(1)
Antibody-based or humoral immunity
549(3)
Structure of antibodies (immunoglobulins)
549(1)
What are the functions of antibodies?
550(1)
There are different classes of antibodies
550(1)
Generation of antibody diversity
550(2)
Activation of B cells to produce antibodies
552(3)
Deletion of potentially self-reacting B cells in the bone marrow
552(1)
The theory of clonal selection
552(1)
B cells must be activated before they can develop into antibody-secreting cells
552(2)
Affinity maturation of antibodies
554(1)
Memory cells
555(1)
Cell-mediated immunity (cytotoxic T cells)
555(2)
Mechanism of action of cytotoxic T cells
556(1)
The role of the major histocompatibility complexes (MHCs) in the displaying of peptides on the cell surface
556(1)
CD proteins reinforce the selectivity of T cell receptors for the two classes of MHCs
557(1)
The immune system needs to be tightly regulated
557(1)
Why does the human immune system reject transplanted human cells?
558(1)
Monoclonal antibodies
558(1)
Humanized monoclonal antibodies
559(1)
Summary
559(1)
Further reading
560(1)
Problems
561(2)
Answers to problems 563(28)
Index of diseases and medically relevant topics 591(2)
Index 593
Dr Despo Papachristodoulou is a Reader in Biochemistry and Medical Education at Kings College London. Her interests include metabolism and nutrition, obesity, diabetes and diabetic complications, medical education and curriculum development. Dr Papachristodoulou has a long experience of teaching Biochemistry and Nutrition to Medical, Dental and Biomedical undergraduates and is lead of the Professional/Graduate Entry to Medicine programme at Kings College.

Dr Alison Snape is Senior Lecturer and Head of the Teaching Department of Biochemistry at King's College London. Her interests include regulation of gene expression and differentiation in early embryonic development. Dr Snape has extensive experience of teaching biochemistry and molecular biology to undergraduates and organises modules that are taken by first year students in bioscience and nutrition programmes.