Biochemistry and molecular biology:
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| Main Authors: | , |
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| Format: | Book |
| Language: | English |
| Published: |
Oxford [u.a.]
Oxford Univ. Press
2009
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| Edition: | 4. ed. |
| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Item Description: | 5. ed. u.d.T.: Despo Papachristodoulou, ... : Biochemistry and molecular biology |
| Physical Description: | XXIX, 568 S. Ill., graph. Darst. |
| ISBN: | 9780199226719 |
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Record in the Search Index
| _version_ | 1804138596985208832 |
|---|---|
| adam_text | Brief contents
Diseases and medically relevant topics xxv
Abbreviations xxvii
Part l Basic concepts of life
1 The basic molecular themes of life 3
2 Cells and viruses 16
3 Energy considerations in biochemistry 27
Part 2 Structure and function of proteins
and membranes
4 The structure of proteins 45
5 Methods in protein investigation 71
6 Enzymes 87
7 The cell membrane and membrane proteins 101
8 Muscle contraction, the cytoskeleton, and
molecular motors 125
Part 3 Metabolism
9 Food digestion, absorption, distribution to the
tissues, and appetite control 145
10 Mechanisms of transport, storage, and mobilization
of dietary components 162
11 Principles of energy release from food 177
12 Glycolysis, the citric acid cycle, and the electron
transport system 188
13 Energy release from fat 216
14 Synthesis of fat and related compounds 223
15 Synthesis of glucose (gluconeogenesis) 236
16 Strategies for metabolic control and their
application to carbohydrate and fat metabolism 243
17 Why should there be an alternative pathway of
glucose oxidation? The pentose phosphate pathway 267
18 Raising electrons of water back up the energy
scale - photosynthesis 272
19 Amino acid metabolism 282
20 Nucleotide synthesis and metabolism 298
Part 4 Information storage and utilization
21 The genome 313
22 DNA synthesis, repair, and recombination 332
23 Gene transcription and control 353
24 Protein synthesis and controlled protein breakdown 380
25 The RNA world - RNA microgenes and RNA
interference 405
26 Protein sorting and delivery 411
27 Cell signalling 429
28 Manipulating DNA and genes 458
Part 5 Molecular biology in health and disease
29 Special topics: blood clotting, xenobiotic
metabolism, reactive oxygen species 483
30 The immune system 493
31 The cell cycle and its control 507
32 Apoptosis 512
33 Cancer 517
Figure acknowledgements 525
Answers to problems 527
Index of diseases and medically relevant topics 554
Index 555
Contents
Preface v
Acknowledgements viii
Diseases and medically relevant topics xxv
Abbreviations xxvii
H^B Parti Basic concepts of life
Chapter 1 The basic molecular themes of life 3
All life forms are similar at the molecular level 3
The energy cycle in life 4
The laws of thermodynamics deal with energy 4
Energy can be transformed from one state to another 5
ATP is the universal energy currency in life 5
Types of molecules found in living cells 6
• Small molecules 7
• Macromolecules are made by polymerization of smaller units 7
• Protein and nucleic acid molecules have information content 7
Proteins 8
• Catalysis of reactions by enzyme proteins is central to
the existence of life 8
• Why are enzymes needed? 8
Proteins work by molecular recognition 9
• Life is self-assembling due to molecular recognition
by proteins 9
• Many proteins are molecular machines 9
• How can one type of molecule do so many tasks? 9
Evolution of proteins 9
• Development of new genes 9
DNA 10
• DNA directs its own replication 10
• Genetic code 10
Organization of the genome 12
How did life start? 12
• The RNA world 13
Proteomics and genomics 13
Summary 14
Further reading 15
Problems 15
Chapter 2 Cells and viruses 16
Cells are the units of all living systems 16
• Why are cells microscopic in size? 16
Classification of organisms 16
• Prokaryotic cells 17
• Eukaryotic cells 18
• Basic types of eukaryotic cells 21
Box 2.1 Some of the organisms used in experimental
biochemical research 22
Viruses 23
Box 2.2 Structure of the drugazidothymidine 25
Summary 25
Further reading 26
Problems 26
Chapter 3 Energy considerations in
biochemistry 27
• Energy considerations determine whether a chemical
reaction is possible in the cell 27
• Reversible and irreversible reactions and AG values 28
• The importance of irreversible reactions in the strategy of
metabolism 29
• Why is this metabolic strategy used in the cell? 29
• How are AG values obtained? 30
• Standard free energy values and equilibrium constants 30
The release and utilization of free energy from food 30
ATP is the universal energy intermediate in all life 31
• What are the structural features of high-energy phosphate
compounds 31
Box 3.1 Henderson-Hasselbalch equation calculation 32
• The structure of ATP 33
• What transports the—©around the cell? 33
• How does ATP drive chemical work? 34
Box 3.2 Calculation of AG value 35
• How does ATP drive other types of work? 35
• High-energy phosphoryl groups are transferred by
kinase enzymes 35
¦Hi Contents
Energy considerations in covalent and noncovalent
bonds 36
• Noncovalent bonds are the basis of molecular recognition
and self-assembly of life forms 36
• Noncovalent bonds are also important in the structures of
individual protein molecules and other macromolecules 37
• Types of noncovalent bonds 37
Appendix: Buffers and p/f, values 38
• pKa values and their relationship to buffers 39
Summary 40
Further reading 41
Problems 41
p§«t7J Part 2 Structure and function
RgSji of proteins and membranes
Chapter 4 The structure of proteins 45
Structures of the 20 amino acids used in protein
synthesis 45
The different levels of protein structure - primary,
secondary, tertiary, and quaternary 47
• Primary structure of proteins 48
• Secondary structure of proteins 49
• Tertiary structure of proteins 51
• Quaternary structure of proteins 54
Protein homologies and evolution $4
Protein domains 55
• Domain shuffling 55
• Membrane proteins 56
• Conjugated proteins and post-translationat modifications
of proteins 56
Extracellular matrix proteins 56
• Structure of collagens 57
Box 4.1 Genetic diseases of collagen 58
• Structure of elastin 58
• Structure of proteoglycans 58
Box 4.2 Smoking, elastin, emphysema, and proteinases 59
• Adhesion proteins of the extracellular matrix 60
• Integrins are important signalling proteins 60
• Cell adhesion proteins 61
Myoglobin and haemoglobin illustrate how protein
structure is related to function 62
• Myogtobin 62
• Structure of haemoglobin 63
• Binding of oxygen to haemoglobin 63
• Theoretical models to explain protein allosterism 64
• Mechanism oftheallosteric change in haemoglobin 65
• The essential role of 2:3-bisphosphoglycerate (BPG) in
haemoglobin function 65
• Effect of pH on oxygen binding to haemoglobin 66
Box 4.3 Sickle cell anaemia and thalassaemias 68
Summary 68
Further reading 69
Problems 70
Chapter 5 Methods in protein investigation 71
Purification of proteins 71
• Column chromatography 72
• SDS polyacrylamide gel electrophoresis 73
• Nondenaturing polyacrylamide gel electrophoresis 73
The principles of mass spectrometry 74
• Mass spectrometers consist of three principal components 75
• lonization methods for protein and peptide mass
spectrometry 75
• Types of mass analysers 76
• Types of mass spectrometers 76
• Identification of proteins using mass spectrometry without
sequencing 76
Identification of proteins by limited sequencing and
database searching 77
Methods of sequencing protein 77
• Classic methods 77
• Sequence analysis of proteins from gene DNA sequences 78
• Sequencing by mass spectrometry 78
• Molecular weight determination of proteins 78
• Analysis of post-translational modification of proteins 78
Determination of the three-dimensional structure
of proteins 78
• X-ray diffraction 78
• Nuclear magnetic resonance spectroscopy 79
• Homology modelling 79
• An exercise in obtaining a 3-D structure from a protein
database 79
Proteomics and mass spectrometry 79
Bioinformatics and databases 80
Box 5.1 Database of website addresses 80
• A bioinformatics overview 81
Appendix: Introduction to obtaining molecular structures
of proteins starting with data from the Protein Data Bank 81
• Steps in displaying the human haemoglobin molecule 82
Summary **
Further reading 85
Problems •
Chapter 6 Enzymes 87
Enzyme catalysis 87
• The nature of enzyme catalysis 88
• The induced-fit mechanism of enzyme catalysis 89
Enzyme kinetics 90
• Hyperbolic kinetics of a classical enzyme 90
• Allosteric enzymes 91
General properties of enzymes 92
• Nomenclature of enzymes 92
• Isozymes 92
• Enzyme cofactors and activators 92
• Effect of pH on enzymes 92
• Effect of temperature on enzymes 92
• Effect of inhibitors on enzymes 93
• Competitive and noncompetitive inhibitors 93
Mechanism of enzyme catalysis 94
• Mechanism of the chymotrypsin reaction 94
• The catalytic triad of the active centre 95
• The reactions at the catalytic centre of chymotrypsin 96
• What is the function of the aspartate residue of the
catalytic triad? 97
• Other serine proteases 97
• A brief description of other types of protease 98
Summary 98
Further reading 99
Problems 100
Chapter 7 The cell membrane and membrane
proteins 101
Basic lipid architecture of membranes 101
• The polar lipid constituents of cell membranes 101
• What are the polar groups attached to the phosphatidic acid? 103
• Membrane lipid nomenclature 105
• Why are there so many different types of membrane lipid? 105
• The fatty acid components of membrane lipids 106
• What is cholesterol doing in membranes? 106
• The self-sealing character of the lipid bilayer 106
Box 7.1 Trans fatty acids 107
• Permeability characteristics of the lipid bilayer 108
Membrane proteins and membrane design 108
Structures of integral membrane proteins 108
• Anchoring of peripheral membrane proteins to membranes no
• Glycoproteins 110
Functions of membranes no
• Membrane transport 110
Contents fl^^^J
Box 7.2 Calculation of energy required for transport 111
Box 7.3 Cardiac glycosid es 111
• Passive transport or facilitated diffusion 113
• Gated ion channels 113
• Mechanism of the selectivity of the potassium channel 115
• Nerve-impulse transmission 116
Box 7.4 Cholinesterase inhibitors and Alzheimer s disease 117
• Myelinated neurons permit more rapid nerve-impulse
transmission 120
Box 7.5 Membrane-targeted antibiotics 121
• Role of the cell membrane in maintaining the shape
of the cell 121
• Cell-cell interactions - tight junctions, gap junctions,
and cellular adhesive proteins 122
Summary 122
Further reading 123
Problems 124
Chapter 8 Muscle contraction, the cytoskeleton,
and molecular motors 125
Muscle contraction 125
• A reminder of conformational changes in proteins 125
Types of muscle cell and their energy supply 125
• Structure of skeletal striated muscle 126
• How does the myosin head convert the energy of ATP
hydrolysis into mechanical force on the actin filament? 127
Box 8.1 Muscular dystrophy 130
Control of voluntary striated muscle 131
Box 8.2 Malignant hyperthermia 131
• How does Ca2+trigger contraction? 131
Smooth muscle differs in structure and control from
striated muscle 132
• Control of smooth muscle contractions 132
The cytoskeleton 133
• The cytoskeleton is in a constant dynamic state 134
The role of actin and myosin in nonmuscle cells 134
• Assembly and collapse of actin filaments 134
• The role of actin and myosin in intracellular transport
ofvesicles 135
Microtubules, cell movement, and intracellular transport 136
Box 8.3 Effects of drugs on the cytoskeleton 138
Intermediate filaments 138
Summary 139
Further reading 139
Problems 141
^^^^H Contents
^HJ Part 3 Metabolism
Chapter 9 Food digestion, absorption,
distribution to the tissues, and appetite control 145
Chemistry of foodstuffs 145
Digestion and absorption 146
• Anatomy of the digestive tract 146
• What are the energy considerations in digestion and
absorption? 146
• A major problem in digestion - why doesn t the body
digest itself? 146
Digestion of proteins 146
• HCI production in the stomach 147
• Pepsin, the proteolytic enzyme of the stomach 147
• Completion of protein digestion in the small intestine 147
• Activation of the pancreatic proenzymes 148
• Absorption ofamino acids into the bloodstream 148
Digestion of carbohydrates 148
• Structure of carbohydrates 148
• Digestion of starch 149
• Digestion of sucrose 150
• Digestion of lactose 150
• Absorption of monosaccharides 150
Digestion and absorption of fat 151
• ResynthesisofTAG in intestinal cells 152
• Chylomicrons 152
Digestion of other components of food 153
Storage of food components in the body 153
• How are the different food components stored in cells? 153
• Characteristics of different tissues in terms of energy
metabolism 155
• Overall control of fuel distribution in the body by hormones 156
• Postprandial condition 156
• Fasting condition 156
• Prolonged fasting or starvation 156
• The emergency situation - fight or flight 157
Regulation of food intake: appetite control 157
• Hormones that control appetite 157
• The hypothalamus integrates appetite control hormone
effects 158
Summary 159
Further reading 160
Problems 160
Chapter 10 Mechanisms of transport, storage,
and mobilization of dietary components 162
Glucose traffic in the body 162
• Mechanism of glycogen synthesis 162
• Breakdown of glycogen to release glucose into the blood 165
• Key issues in the interconversion of glucose and glycogen 167
• Why does liver have glucokinase and the other tissues,
hexokinase? 167
• What happens to other sugars absorbed from the intestine? 168
Box 10.1 Uridyltransferase deficiency and galactosaemia 169
Amino acid traffic in the body 0n terms of fuel logistics) 169
Fat and cholesterol traffic in the body 169
• Uptake of fat from chylomicrons into cells 169
Logistics of fat and cholesterol movement in the body 170
• An overview 170
• Utilization of cholesterol in the body 171
• Lipoproteins involved in fat and cholesterol movement
in the body 171
• Apolipoproteins 171
• Mechanism of TAG and cholesterol transport from the liver
and the reverse cholesterol transport in the body 171
Box 10.2 Inhibitors of cholesterol synthesis 174
• Release of FFA from adipose cells 174
• How are FFA carried in the blood? 174
Summary 175
Further reading 175
Problems 176
Chapter 11 Principles of energy release from
food 177
Overview of glucose metabolism 177
• Biological oxidation and hydrogen-transfer systems 177
Energy release from glucose 179
• The main stages of glucose oxidation 179
• Stage 1 in the release of energy from glucose: glycolysis 179
• Stage 2 of glucose oxidation: the citric acid cycle 180
• Stage 3 of glucose oxidation: electron transport to
oxygen 182
• The electron transport chain - a hierarchy of electron
carriers 182
Box ll.l Calculation of the relationship between AG0
value and the Rvalue 183
Energy release from oxidation of fat 185
Energy release from oxidation of amino acids 185
The interconvertibility of fuels 185
Box 11.2 A survey of vitamins 186
Summary 187
Problems 187
Chapter 12 Glycolysis, the citric acid cycle,
and the electron transport system 188
Stage 1 - glycolysis 188
• Glucose or glycogen? 188
• WhyuseATPhereatthebeginningofglycolysis? 188
• Interconversion of dihydroxyacetone phosphate and
gtyceraldehyde-3-phosphate 191
• Glyceraldehyde-3-phosphate dehydrogenase - an
oxidation linked to ATP synthesis 191
• The final steps in glycolysis 192
• Anaerobic glycolysis 193
• The ATP balance sheet from glycolysis 193
• Transport of pyruvate into the mitochondria 193
Conversion of pyruvate to acetyl-CoA - a preliminary
step before the citric acid cycle 193
• Components involved in the pyruvate dehydrogenase
reaction 194
Stage 2 - the citric acid cycle 194
• A simplified version of the citric acid cycle 195
• Mechanisms of the citric acid cycle reactions 195
• What determines the direction of the citric acid cycle? 198
• Stoichiometry of the cycle 198
• Topping up the citric acid cycle 198
Stage 3 - the electron transport chain that conveys
electrons from NADH and FADH2 to oxygen 200
• The electron transport chain 200
• Oxidative phosphorylation - the generation of ATP coupled
to electron transport 203
• How are protons ejected? 204
• ATP synthesis by ATP synthase is driven by the proton
gradient 206
• Structure of ATP synthase 206
• The F, unit and its role in the conversion of ADP+P,to ATP 206
• Structure oftheF0 unit and its role 208
• Mechanism by which proton flow causes rotation of Fo 209
• Transport ofADP into mitochondria and ATP out 210
• Reoxidation of cytoplasmic NADH from glycolysis by electron
shuttle systems 210
• The balance sheet of ATP production by electron
transport 212
• Yield of ATP from the oxidation of a molecule of glucose to
CO2andH2O 212
• Is ATP production the only use that is made of the potential
energy in the proton-motive force? 213
Box 12.1 Inhibitors and uncouplers of oxidative
phosphorylation 213
Contents HjHH
Summary 213
Further reading 214
Problems 215
Chapter 13 Energy release from fat 216
Mechanism of acetyt-CoA formation from fatty acids 216
• Activation of fatty acids by formation of fatty acyl-CoA
derivatives 216
• Transport of fatty acyl-CoA derivatives into mitochondria 217
• Conversion of fatty acyl-CoA to acetyl-CoA molecules inside
the mitochondrion by 0-oxidation 217
• Energy yield from fatty acid oxidation 218
Oxidation of unsaturated fat 218
Oxidation of odd-numbered carbon-chain fatty acids 219
Ketogenesis in starvation and type 1 diabetes mellitis 219
• How is acetoacetate made from acetyl-CoA? 219
• Peroxisomalaxidation of fatty acids 220
• Where to now? 221
Summary 221
Further reading 221
Problems 221
Chapter 14 Synthesis of fat and related
compounds 223
Mechanism of fat synthesis 223
• General principles of the process 223
• Synthesis of malonyl-CoA is the first step 223
• The acyl carrier protein (ACP) and the /3-ketoacyl
synthase 224
• Mechanism of fatty acyl-CoA synthesis 224
• Organization of the fatty acid synthesis process 224
• The reductive steps in fatty acid synthesis 224
• Fatty acid synthesis takes place in the cytoplasm 226
Synthesis of unsaturated fatty acids 227
Box 14.1 Omega fatty acids and diet 227
Synthesis of TAG and membrane Upids from fatty acids 228
Synthesis of membrane Upidbilayer 228
• Synthesis of glycerophospholipids 229
• Synthesis of new membrane lipid bilayer 230
Synthesis of prostagtandins and related compounds 231
• The prostaglandins and thromboxanes 231
Box 14.2 Nonsteroidal anti-inflammatory drugs (NSAIDs) 232
• Leukotrienes 233
• Synthesis of cholesterol 233
• Conversion of cholesterol to steroid hormones 233
gfnHH Contents
Summary 234
Further reading 235
Problems 235
Chapter 15 Synthesis of glucose
(gluconeogenesis) 236
• Mechanism of glucose synthesis from pyruvate 236
• What are the sources of pyruvate used by the liver for
gluconeogenesis? 237
• Synthesis of glucose from glycerol 239
• Synthesis of glucose from propionate 239
• Effects of ethanol metabolism on gluconeogenesis 239
• Synthesis of glucose via the glyoxylate cycle in bacteria
and plants 240
Summary 241
Further reading 242
Problems 242
Chapter 16 Strategies for metabolic control
and their application to carbohydrate and
fat metabolism 243
Why are controls necessary? 243
• The potential danger of futile cycles in metabolism 243
How are enzyme activities controlled? 244
• Metabolic control by varying the amounts of enzymes is
relatively slow 244
• Metabolic control by regulation of the activities of
enzymes in the cell can be effectively instantaneous 245
• Which enzymes in metabolic pathways are regulated? 245
• The nature of control enzymes 245
Allosteric control of enzymes 245
• The mechanism of allosteric control of enzymes 246
• Aspartate transcarbamylase is the classical model of
an allosteric enzyme 247
• Reversibility of allosteric control 247
• Allosteric control is a tremendously powerful metabolic
concept 247
Control of enzyme activity by phosphorylation 248
• Protein kinases and phosphatases are key players in
control mechanisms 248
• Control by phosphorylation usually depends on
chemical signals from other cells 248
General aspects of the hormonal control of metabolism 249
• How do glucagon, epinephrine, and insulin work? 249
• What is a second messenger? 249
• The second messenger for gtucagon and epinephrine is
cyclic AMP 249
Control of carbohydrate metabolism 250
• Control of glucose uptake into cells 250
Control of glycogen metabolism 251
• Control of glycogen breakdown in muscle 252
• Mechanism of muscle phosphorylase activation by cAMP 253
• Control of glycogen breakdown in the liver 254
• Reversal of phosphorylase activation in muscle and liver 254
• The switchover from glycogen breakdown to gtycogen
synthesis 254
• Mechanism of insulin activation of glycogen synthase 255
• Control of glycolysis and gluconeogenesis 255
• Muscle and liver PFK2 enzymes are different 257
• Fructose metabolism and its control differs from that
of glucose 258
• Control of pyruvate dehydrogenase, the citric acid cycle,
and oxidative phosphorylation 258
Controls of fatty acid oxidation and synthesis 259
• Nonhormonal controls 259
• Breakdown of acetyl-CoA carboxylase is a new type of fat
metabolism control 260
• Hormonal controls on fat metabolism 260
Responses to metabolic stress 260
• Response to low ATP levels by AMP-activated protein kinase 261
• Response of cells to oxygen deprivation 261
• Mechanism ofthehypoxia response 261
Integration of fat and carbohydrate metabolism
controls in diabetes 262
Summary 263
Further reading 264
Problems 266
Chapter 17 Why should there be an alternative
pathway of glucose oxidation? The pentose
phosphate pathway 267
The pentose phosphate pathway has two main parts 267
• The oxidative section produces equal amounts of
ribose-5-phosphate and NADPH 268
• Conversion of surplus ribose-5-phosphate to
glucose-6-phosphate 268
• Conversion of glucose-6-phosphate to ribose-5-phosphate
without NADPH generation 270
• Generation of NADPH without net production of
ribose-5-phosphate 270
Box 17.1 Why do red blood cells have the pentose
phosphate pathway? 270
Summary 271
Further reading 271
Problems 271
Chapter 18 Raising electrons of water back up
the energy scale - photosynthesis 272
• Overview 272
• Site of photosynthesis -the chloroplast 272
The light-dependent reactions of photosynthesis 273
• The photosynthetic apparatus and its organization in
the thylakoid membrane 273
• How is tight energy captured? 274
• Mechanism of light-dependent reduction of NADP+ 275
• Photosystem II 275
• Photosystem I 276
• How is ATP generated? 276
The dark reactions of photosynthesis - the Calvin
cycle 276
• How is CO2 converted to carbohydrate? 276
• Rubisco has an apparent efficiency problem 278
• The C4 pathway 279
Summary 280
Further reading 280
Problems 280
Chapter 19 Amino acid metabolism 282
Nitrogen balance of the body 283
General metabolism of amino acids 283
• Aspects of amino acid metabolism 283
• Glutamate dehydrogenase has a central rote in the
deamination of amino acids 284
• Fate of the keto acid or carbon skeletons of deaminated
amino acids 285
• Genetic errors in amino acid metabolism cause diseases 286
• Methionine and transfer of methyl groups 287
Synthesis of amino acids 288
• Synthesis of glutamic acid 288
• Synthesis ofaspartic acid and alanine 288
• Synthesis of serine 289
• Synthesis of gtycine 289
Haem and its synthesis from glycine 289
Box 19.1 Acute intermittent porphyria 291
• Destruction of haem 291
• Synthesis of epinephrine and norepinephrine 292
The urea cycle 292
• Mechanism of arginine synthesis 293
• Conversion of citrulline to arginine 293
• Transport of the amino nitrogen from extrahepatic
tissues to the liver 294
Contents ^^^|
• Diseases due to urea cycle deficiencies 295
• Alternatives to urea formation exist in different animals 295
Summary 295
Further reading 296
Problems 296
Chapter 20 Nucleotide synthesis and
metabolism 298
Structure and nomenclature of nucleotides 298
• The sugar component of nucleotides 298
• The base component of nucleotides 299
• Attachment of the bases in nucleotides 299
Synthesis of purine and pyrimidine nucleotides 300
• Purine nucleotides 300
• The purine salvage pathway 304
• Formation of uric acid from purines 305
• Control of purine nucleotide synthesis 305
• Synthesis of pyrimidine nucleotides 305
• How are deoxyribonucleotides formed? 306
Medical effects of folate deficiencies 307
• Thymidylate synthesis is targeted by anticancer agents
such as the antifolate, methotrexate 307
Summary 308
Further reading 309
Problems 309
I f I Part 4 Information storage
li^NiJ and utilization
Chapter 21 The genome 313
• A brief overview 313
• The prokaryotic genome 313
• The eukaryotic genome 313
The structures of DNA and RNA 314
• DNA is chemically a very simple molecule 314
• DNA and RNA are both nucleic acids 314
The primary structure of DNA 314
• There are four different nucleotide bases in DNA 315
• Attachment of the bases to deoxyribose 315
• The physical properties of the polynucleotide
components 315
• Structure of the polynucleotide of DNA 315
SK wKjjfS Contents
• Why is deoxyribose used in DNA rather than ribose? 316
• Why does RNA have uracil and DNA thymine? 317
The DNA double helix 317
• Complementary base-pairing 317
• DNA chains are antiparallel; what does this mean? 320
How is the DNA packed into a nucleus? 321
• The packing of the prokaryotic genome is different from
that in eukaryotes 322
The packing of DNA in the eukaryotic nucleus changes
during the cell life cycle 323
• The tightness of DNA packing is the initial control on
gene activity 324
• The mitochondrial genome 325
The structure of protein-coding genes 326
• Protein-coding regions of genes in eukaryotes are split
up into different sections 326
Box 21.1 Size of genomes related to complexity of
organisms 327
• Multiple gene copies facilitate evolution of new genes 327
Views on so-called junk DNA have changed dramatically 327
• The newly discovered microRNA genes of junk DNA are
revolutionizing important concepts of gene control 327
• Transposons 328
• Repetitive DNA sequences 328
• Pseudogenes 328
Summary 329
Further reading 329
Problems 330
Chapter22 DNA synthesis, repair, and
recombination 332
Overall principle of DNA repUcation 332
Control of initiation of DNA replication in £ coli 333
Initiation and regulation of DNA replication in
eukaryotes 333
Unwinding the DNA double helix and supercoiling 334
• How are positive supercoils removed ahead of the
replicative fork? 335
The basic enzymic reaction catalysed by DNA
polymerases 336
How does a new strand get started? 337
The polarity problem in DNA replication 337
Mechanism of Okazaki fragment synthesis 338
• Enzyme complex at the replicative fork inf. coli 338
• Processing the Okazaki fragments 340
The machinery in the eukaryotic replicative fork 341
How is fidelity achieved in DNA replication? 342
• Exonucleolytic proofreading 342
• Methyl-directed mismatch repair 343
Repair of DNA damage in Lcoli 344
Tetomeres solve the problem of replicating the ends
of eukaryotic chromosomes 345
• How is telomeric DNA synthesized? 346
• Telomere shortening correlates with ageing 347
• Telomeres stabilize the ends of linear chromosomes 347
DNA damage repair in eukaryotes 347
Replication of mitochondrial DNA 347
DNA synthesis by reverse transcription in retroviruses 347
Homologous recombination 348
• Mechanism of homologous recombination in E. coli 348
• Recombination in eukaryotes 350
Summary 350
Further reading 351
Problems 352
Chapter 23 Gene transcription and control 353
Messenger RNA 353
• The structure of RNA 353
• How is mRNA synthesized? 353
• Some general properties of mRNA 354
• Some essential terminology 355
Gene transcription in £ coli 355
• What do we mean by the 5 end of a gene? 355
• Phases of gene transcription 356
• The rate of gene transcription initiation in prokaryotes 357
• Control of transcription by different sigma factors 357
• Gene control inf. coli: the tocoperon 357
• Structure of the £ coli tocoperon 358
Gene transcription in eukaryotic cells 359
• Capping the RNA transcribed by RNA polymerase II 360
• Split genes 360
Ribozymes and self-splicing of RNA 361
Mechanism of initiation of eukaryotic gene transcription
and its control 362
• Unpacking of the DNA for transcription 362
• A general overview of the differences in the initiation
and control of gene transcription in prokaryotes and
eukaryotes 363
• Types of eukaryotic genes and their controlling regions 364
• Most transcription factors themselves are regulated 366
• How do transcription factors promote transcriptional
initiation? 367
• How is transcription initiated on the opened promoter? 368
• Transcription repressors 369
Discovery of the mediator 369
The RNA polymerase II of eukaryotic cells 370
• Termination of transcription in eukaryotic cells 371
• Switching off the gene 371
DNA methylation affects gene transcription 371
• Possible roles of DNA methylation in gene silencing 372
mRNA stability and the control of gene expression 372
• Determinants of mRNA stability and their role in gene
expression control 372
Gene transcription in mitochondria 373
• Editing of mRNAs 373
Transcription of noncoding genes 373
DNA-binding proteins 374
Summary 376
Further reading 377
Problems 379
Chapter 24 Protein synthesis and controlled
protein breakdown 380
Essential basis of the process of protein synthesis 380
• The genetic code 381
A preliminary simplified look at the chemistry of peptide
synthesis 381
• How are the codons translated? 383
• Transfer RNA 383
• The wobble mechanism 384
• How are amino acids attached to tRNA molecules? 384
Ribosomes 386
Initiation of translation 386
• Initiation of translation in f. coli 387
Once initiation is achieved, elongation is the next step 388
• Cytoplasmic elongation factors in E.coli 388
• Mechanism of elongation in E.coli 388
• How is accuracy of translation achieved? 390
Mechanism of translocation on the £ coli ribosome 390
Box 24.1 Effects of antibiotics and toxins on protein
synthesis 391
Termination of protein synthesis in £ coli 391
Physical structure of the ribosome 392
• What is a polysome? 392
Riboswitches 392
Contents aSHS
Protein synthesis in eukaryotes 393
• Incorporation of selenocysteine into proteins 393
Protein synthesis in mitochondria 394
Folding up of the polypeptide chain 395
• Chaperones (heat shock proteins) 395
Mechanism of action of molecular chaperones 395
• Enzymes involved in protein folding 397
Protein folding and priori diseases 397
Translational control mechanisms 397
• Regulation of globin synthesis 397
• Transtational control of proteins involved in haem
synthesis and iron metabolism 398
Programmed destruction of protein by proteasomes 399
• The structure of proteasomes 399
• Proteins destined for destruction in proteasomes are
marked by ubiquitination 399
• The rote of proteasomes in the immune system 400
Summary 401
Further reading 402
Problems 404
Chapter 25 The RNA world - RNA microgenes
and RNA interference 405
• A general overview 405
• MicroRNAs and the functioning of the human genome 405
RNA interference (RNAi) is a method of gene silencing
triggered by double-stranded RNA 406
• MicroRNAs are double-stranded hairpin molecules 407
• Molecular mechanism of gene silencing by RNAi 407
The potential medical and practical importance of RNAi 407
• MicroRNAs may orchestrate expression of protein-coding
genes in eukaryotes 408
Summary 409
Further reading 409
Problems 410
Chapter 26 Protein sorting and delivery 411
A preliminary overview of the field 411
• Structure and function oftheER and Golgi apparatus 413
The importance of the GTP/GDP switch mechanism in
protein targeting 414
Translocation of proteins through the ER membrane 414
• Folding ofthepolypeptides inside the ER 415
• Glycosylation of proteins in the ER lumen and Golgi apparatus 415
H^^B Contents
• Vesicles involved in protein translocation from the ER
and Golgi 416
• Proteins for lysosomes 416
Box 26.1 Lysosomal storage disorders 416
Proteins are sorted, packaged, and despatched from
the Golgi to various destinations 416
• Clathrin-coated vesicles transport enzymes from the
Golgi to lysosomes 416
• Proteins to be returned to the ER 417
• Proteins to be secreted from the cell 417
Mechanism of COP-coated vesicle formation 418
• How does a vesicle find its target membrane? 418
Synthesis of integral membrane proteins and their
transport 418
Posttranslational transport of proteins into organelles 420
• Transport of proteins into mitochondria 420
• Mitochondrial matrix proteins are synthesized as
preproteins 420
• Delivery of proteins to mitochondrial membranes and
intermembrane space 421
Nuclear-cytoplasmic traffic 421
The nuclear pore complex 422
Nuclear localization signals 423
• Where does the energy for nuclear transport come from? 424
• Regulation of nuclear transport by cell signals and its role
in gene control 425
Summary 426
Further reading 426
Problems 428
Chapter 27 Celt signalling 429
Overview 429
• Organization of this chapter 431
What are the signalling molecules? 431
• Neurotransmitters 431
• Hormones 431
• Cytokines and growth factors 432
• Vitamin D and retinoic acid 433
Responses mediated by intracellular receptors 433
Box 27.1 The glucocorticoid receptor and anti-inflammatory
drugs 434
Responses mediated by receptors in the cell membrane 435
• There are two types of membrane-bound receptors 435
General concepts in cell signalling mechanisms 436
• Protein phosphorylation 436
• Binding domains of signal transduction proteins 436
• Terminating signals 437
Examples of signal transduction pathways 437
Signal transduction pathways from tyrosine kinase
receptors 437
• The Ras pathway 437
Box 27.2 Some deadly toxins work by increasing or
inhibiting dephosphorylation of proteins 440
• Signal sorting 441
• The phosphatidylinositide 3-kinase (PI 3-kinase) pathway
and insulin signalling 441
• The JAK/STAT pathways: another type of tyrosine
kinase-associated signalling system 443
G-protein-coupled receptors and associated signal
transduction pathways 444
• cAMP as second messenger: epinephrine signalling -
a G-protein pathway 444
• The phosphatidylinositot cascade: another example of a
G-protein-coupled receptor which works via a different
second messenger 447
• Other control roles of calcium 448
• Vision: a process dependent on a G-protein-coupled
receptor 448
Signal transduction pathway using cGMP as second
messenger 451
• Membrane receptor-mediated pathways 451
• Nitric oxide signalling - activation of a soluble cytoplasmic
guanylate cyclase 451
Summary 453
Further reading 454
Problems 457
Chapter 28 Manipulating DNA and genes 458
Basic methodologies 458
• Some preliminary considerations 458
• Cutting DNA with restriction endonucleases 459
• Separating DNA pieces 459
• Visualizing the separated pieces 460
• Detection of specific DNA fragments by nucleic acid
hybridization probes 460
• Southern blotting 460
Sequencing DNA 460
• The principle of DNA sequencing by the chain termination
method 460
Amplification of DNA by the polymerase chain reaction 462
• Analysis of multiple gene expression in celts using DNA
microarrays 463
Joining DNA to form recombinant molecules 464
Cloning DNA 465
• Cloning in ptasmids 465
• Cloning using bacteriophage A as vector 466
• Cloning very large pieces of DNA 467
Applications of recombinant DNA technology 468
• Production of human and other proteins 468
• Preparation ofacDNA library 468
• Expressing the cDNA in E. coli 468
• Site-directed mutagenesis 469
• PCR in forensic science 470
• Locating disease-producing genes 470
Box 28.1 Repetitive DNA sequences 471
• Knockout mice 472
• The embryonic stem (ES) cell system 473
• Gene targeting 473
• Stem cells and potential therapy for human diseases 475
• Transgenic animals and gene therapy 476
DNA databases and genomics 476
Summary 477
Further reading 478
Problems 479
• Part 5 Molecular biology in
health and disease
Chapter 29 Special topics: blood clotting,
xenobiotic metabolism, reactive oxygen species 483
Blood clotting 483
• What are the signals that clot formation is needed? 484
• How does thrombin cause thrombus (clot) formation? 484
• Keeping clotting in check 485
• Rat poison, blood clotting, and vitamin K 485
Protection against ingested foreign chemicals
(xenobiotics) 486
• Cytochrome P450 486
• Secondary modification - addition of a polar group to
products oftheP450 attack 487
• Medical significance of P450s 487
• Muttidrug resistance 488
Protection against reactive oxygen species 488
• Formation of the superoxide anion and other reactive
oxygen species 488
Box 29.1 Red wine and cardiovascular health 489
• Mopping up oxygen free radicals with vitamins C and E 490
• Enzymic destruction of superoxide by superoxide dismutase 490
Contents fl|^|
The glutathione peroxidase-glutathione reductase
strategy 490
Summary 490
Further reading 491
Problems 492
Chapter 30 The immune system 493
Overview 493
• The innate immune system 493
• The adaptive immune response 493
• The problem of autoimmune reactions 494
• The cells involved in the immune system 494
• There are two arms to the adaptive immune response 494
• Where is the immune system located in the body? 494
Antibody-based or humoral immunity 495
• Structure of antibodies (immunoglobulins) 495
• What are the functions of antibodies? 495
• The different classes of antibodies 495
• Generation of antibody diversity 496
Activation of B cells to produce antibodies 497
• Deletion of potentially self-reacting B cells in the bone
marrow 497
• The theory of clonal selection 497
• B cells must be activated before they can develop into
antibody-secreting cells 498
• Affinity maturation of antibodies 499
• Memory cells 499
Cell-mediated immunity (killer T cells) 499
• Mechanism of action of killer T cells 501
• The role of the major histocompatibility complexes (MHCs)
in the displaying of peptides on the cell surface 501
• CD proteins reinforce the selectivity of T cell receptors for
the two classes of MHCs 502
Why does the human immune system reject transplanted
human cells? 502
Monoclonal antibodies 502
• Humanized monoclonal antibodies 503
Summary 504
Further reading 505
Problems 506
Chapter 31 The cell cycle and its control 507
The eukaryotic cell cycle 507
• The cell cycle is divided into separate phases 507
• The celt cycle phases are tightly controlled 507
¦frUm Contents
Cell cycle controls 508
• Cytokines and growth factor control in the cell cycle 508
• Cell cycle checkpoints 508
• Cell cycle controls depend on the synthesis and
destruction of cyclins 508
Controls in G, are complex 509
• The Gj checkpoint 509
• How is DNA damage detected? 510
Progression to S phase 510
Progression to M phase 510
Mitosis phase 510
Summary 511
Further reading 511
Problems 511
Chapter 32 Apoptosis 512
Overview 512
• What is the purpose of apoptosis? 512
There are two broad methods of initiating apoptosis 513
• Mechanism of an intrinsic pathway of apoptosis 513
• Regulation of the intrinsic pathway of apoptosis 513
• Mechanism of the extrinsic pathway of apoptosis 514
Summary 515
Further reading 515
Problems 516
Chapter 33 Cancer 517
General concepts 517
Malignant Darwinism: cancer development involves an
evolutionary progression of mutations 518
• Development of colorectal cancer 519
Mutations cause cancer 519
Tumour promoters 519
The types of genetic change involved in cancer 520
Oncogenes 520
• How are oncogenes acquired? 520
Tumour-suppression genes 521
• Mechanism of protection by the p53 gene 522
• Mechanism of protection by the retinoblastoma gene 522
Molecular biology advances have potential for
development of new cancer therapies 522
Summary 523
Further reading 523
Problems 524
Figure acknowledgements 525
Answers to problems 527
Index of diseases and medically relevant topics 554
Index 555
Diseases and
topics
Box 2.1 Some of the organisms used in experimental
biochemical research 22
Box 2.2 Structure of the drug azidothymidine 25
Box 3.1 Henderson-Hasselbalch equation calculation 32
Box 3.2 Calculation of AC value 35
Box 4.1 Genetic diseases of collagen 58
Box 4.2 Smoking, elastin, emphysema, and proteinases 59
Box 4.3 Sickle cell anaemia and thalassaemias 68
Box 5.1 Database of website addresses 80
Box 7.1 Trans fatty acids 107
Box 7.2 Calculation of energy required for transport 111
Box 7.3 Cardiac glycosides 111
Box 7.4 Cholinesterase inhibitors and Alzheimer s disease 117
Box 7.5 Membrane-targeted antibiotics 121
Box 8.1 Muscular dystrophy 130
Box 8.2 Malignant hyperthermia 131
Box 8.3 Effects of drugs on the cytoskeleton 138
Box 10.1 Uridyltransferase deficiency and galactosaemia 169
medically relevant
Box 10.2 Inhibitors of cholesterol synthesis 174
Box 11.1 Calculation of the relationship between AG° value
and the E o value 183
Box 11.2 A survey of vitamins 186
Box 12.1 Inhibitors and uncouplers of oxidative
phosphorylation 213
Box 14.1 Omega fatty acids and diet 227
Box 14.2 Nonsteroidal anti-inflammatory drugs (NSAIDs) 232
Box 17.1 Why do red blood cells have the pentose phosphate
pathway? 270
Box 19.1 Acute intermittent porphyria 291
Box 21.1 Size of genomes related to complexity of organisms 327
Box 24.1 Effects of antibiotics and toxins on protein synthesis 391
Box 26.1 Lysosomal storage disorders 416
Box 27.1 The glucocorticoid receptor and anti-inflammatory
drugs 434
Box 27.2 Some deadly toxins work by increasing or
inhibiting dephosphorylation of proteins 440
Box 28.1 Repetitive DNA sequences 471
Box 29.1 Red wine and cardiovascular health 489
|
| any_adam_object | 1 |
| author | Elliott, William H. Elliott, Daphne C. |
| author_facet | Elliott, William H. Elliott, Daphne C. |
| author_role | aut aut |
| author_sort | Elliott, William H. |
| author_variant | w h e wh whe d c e dc dce |
| building | Verbundindex |
| bvnumber | BV035297946 |
| callnumber-first | Q - Science |
| callnumber-label | QP514 |
| callnumber-raw | QP514.2 |
| callnumber-search | QP514.2 |
| callnumber-sort | QP 3514.2 |
| callnumber-subject | QP - Physiology |
| classification_rvk | WD 4010 WD 4150 WE 2400 |
| classification_tum | BIO 210f CHE 800f BIO 780f BIO 220f |
| ctrlnum | (OCoLC)244177280 (DE-599)BVBBV035297946 |
| dewey-full | 572 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 572 - Biochemistry |
| dewey-raw | 572 |
| dewey-search | 572 |
| dewey-sort | 3572 |
| dewey-tens | 570 - Biology |
| discipline | Biologie Chemie |
| edition | 4. ed. |
| format | Book |
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| genre_facet | Lehrbuch |
| id | DE-604.BV035297946 |
| illustrated | Illustrated |
| indexdate | 2024-07-09T21:30:43Z |
| institution | BVB |
| isbn | 9780199226719 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-017102870 |
| oclc_num | 244177280 |
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| physical | XXIX, 568 S. Ill., graph. Darst. |
| publishDate | 2009 |
| publishDateSearch | 2009 |
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| publisher | Oxford Univ. Press |
| record_format | marc |
| spelling | Elliott, William H. Verfasser aut Biochemistry and molecular biology William H. Elliott and Daphne C. Elliott 4. ed. Oxford [u.a.] Oxford Univ. Press 2009 XXIX, 568 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier 5. ed. u.d.T.: Despo Papachristodoulou, ... : Biochemistry and molecular biology Biochemistry Molecular Biology Molecular biology Molekularbiologe (DE-588)1023071983 gnd rswk-swf Biochemie (DE-588)4006777-4 gnd rswk-swf Molekularbiologie (DE-588)4039983-7 gnd rswk-swf 1\p (DE-588)4123623-3 Lehrbuch gnd-content Biochemie (DE-588)4006777-4 s Molekularbiologie (DE-588)4039983-7 s 2\p DE-604 Molekularbiologe (DE-588)1023071983 s 3\p DE-604 Elliott, Daphne C. Verfasser aut HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=017102870&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 2\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 3\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk |
| spellingShingle | Elliott, William H. Elliott, Daphne C. Biochemistry and molecular biology Biochemistry Molecular Biology Molecular biology Molekularbiologe (DE-588)1023071983 gnd Biochemie (DE-588)4006777-4 gnd Molekularbiologie (DE-588)4039983-7 gnd |
| subject_GND | (DE-588)1023071983 (DE-588)4006777-4 (DE-588)4039983-7 (DE-588)4123623-3 |
| title | Biochemistry and molecular biology |
| title_auth | Biochemistry and molecular biology |
| title_exact_search | Biochemistry and molecular biology |
| title_full | Biochemistry and molecular biology William H. Elliott and Daphne C. Elliott |
| title_fullStr | Biochemistry and molecular biology William H. Elliott and Daphne C. Elliott |
| title_full_unstemmed | Biochemistry and molecular biology William H. Elliott and Daphne C. Elliott |
| title_short | Biochemistry and molecular biology |
| title_sort | biochemistry and molecular biology |
| topic | Biochemistry Molecular Biology Molecular biology Molekularbiologe (DE-588)1023071983 gnd Biochemie (DE-588)4006777-4 gnd Molekularbiologie (DE-588)4039983-7 gnd |
| topic_facet | Biochemistry Molecular Biology Molecular biology Molekularbiologe Biochemie Molekularbiologie Lehrbuch |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=017102870&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT elliottwilliamh biochemistryandmolecularbiology AT elliottdaphnec biochemistryandmolecularbiology |