39. Functional Biochemistry In Health And Disease

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39. Functional Biochemistry In Health And Disease



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Preface xi
Abbreviations xiii
1 The Structural and Biochemical
Hierarchy of a Cell and a Human 3
Cell structure 3
Tissues 8
The whole human 10
The biochemical hierarchy 13
2 Energy: In the Body, Tissues and
Biochemical Processes 17
Energy transformations in the whole body 18
Energy transformations in tissues and organs 26
Energy transformation in biochemical reactions and
pathways 28
Adenosine triphosphate: its role in the cell 32
3 Enzymes: Activities, Properties,
Regulation and Physiology 35
Nomenclature and classifi cation 36
Basic facts 37
Mechanisms by which an enzyme enhances
the rate of a reaction 38
Cofactors and prosthetic groups 40
Factors that change the activity of an enzyme 41
Allosteric inhibition 48
The physiological signifi cance of Km and Vmax values 51
Enzymes as tools 54
Enzymes in diagnosis 58
Enzymes as therapeutic agents 59
Enzymes as targets for therapy 59

Kinetic structure of a biochemical pathway 61
Regulation of enzyme activity 63
4 Transport into the Body:
The Gastrointestinal Tract,
Digestion and Absorption 69
Gross structure of the gastrointestinal tract 70
Biochemistry of cooking and food preparation 73
Digestion and absorption 75
The gastrointestinal tract and disease 82
5 Transport into the Cell: Particles,
Molecules and Ions 85
Structure of the plasma membrane 85
Diffusion through membranes 87
Active transport 89
Endocytosis and exocytosis 91
Physiological importance of some transport systems 93
6 Carbohydrate Metabolism 97
Glycolysis 98
The biochemical and physiological importance of
anaerobic glycolysis 104
Regulation of the fl ux through glycolysis 107
Glycogen synthesis 108
Synthesis of Fructose and lactose 110
The pentose phosphate pathway 110
Gluconeogenesis: glucose formation from
non-carbohydrate sources 112
Role of the liver in the regulation of
the blood glucose concentration 117
Hormones and control of gluconeogenesis 123
Regulation of glycolysis and gluconeogenesis
by ATP/ADP concentration ratio in the liver 124
Hypoglycaemia 125
Hyperglycaemia 126

7 Fat Metabolism 127
Fats in nutrition 128
Fat fuels 128
Physiological importance of fat fuels 142
Limitations or drawbacks of fats as a fuel 145
Genetic defects in fatty acid oxidation 146
Pathological concentrations of fat fuels 146
8 Amino Acid and Protein Metabolism 149
Introduction 149
Sources of amino acids 151
Protein and amino acid requirements 155
Fate of amino acids 157
Central role of transdeamination 165
Amino acid metabolism in different tissues 167
Glutamine: an amino acid of central importance 172
Urea ‘salvage’ 177
9 Oxidation of Fuels and ATP
Generation: Physiological and
Clinical Importance 181
The Krebs cycle 181
The electron transfer chain 184
Oxidative phosphorylation 185
Coupling of electron transfer with oxidative
phosphorylation 186
Transport into and out of mitochondria 190
‘Energy’ transport in the cytosol:
the creatine/phosphocreatine shuttle 193
Regulation of fl uxes 194
The physiological importance of mitochondrial
ATP generation 200
The effect of ageing on ATP generation 206
10 Metabolism of Ammonia and
Nucleic Acids 211
Roles of ammonia 211
Urea synthesis 212
Degradation of nucleic acids, nucleotides,
nucleosides and bases: the generation of ammonia 217
Ammonia toxicity 219
Defi ciencies of urea cycle enzymes 220
11 Synthesis of Fatty Acids,
Triacylglycerol, Phospholipids and
Fatty Messengers: The Roles of
Polyunsaturated Fatty Acids 223
Synthesis of long-chain fatty acids 223
Unsaturated fatty acids 229
Essential fatty acids 233
Phospholipids 239
Fatty messenger molecules 243
Fatty acids in neurological and behavioural disorders 251

12 Hormones: From Action in the Cell
to Function in the Body 253
Endocrine hormones: traditional and novel 253
The action, effects and functions of a hormone 256
Action of hormones 257
The biochemical and physiological effects of a hormone 258
Pheromones 264
Kinetic principles that apply to hormone action 266
13 Physical Activity: In Non-Athletes,
Athletes and Patients 275
The mechanical basis of movement by skeletal muscle 275
Structure of muscle 276
Proteins involved in muscle action 279
Mechanism of contraction: the cross-bridge cycle 282
Regulation of contraction 282
Fuels for muscle 286
Fuels for various athletic events and games 291
Fatigue 294
Fatigue in patients 299
Physical training 300
Development of muscle 301
Health benefi ts of physical activity 303
Health hazards of physical activity 303
Skeletal muscle diseases 305
14 Mental Activity and Mental Illness 307
Mental activity 307
Cells in the brain 308
Electrical communication 310
Chemical communication 311
Fuels and energy metabolism in the brain 319
Mental illnesses: biochemical causes 320
Recreational drugs 325
15 Nutrition: Biochemistry,
Physiology and Pathology 331
Basic information required for discussion of
some biochemical aspects of nutrition 331
Vitamins 332
Minerals 345
A healthy diet 350
Nutrition for specifi c activities or conditions 351
Overnutrition 355
Malnutrition 356
Functional foods and nutraceuticals 358
Nutrition for patients with genetic disorders 359
Vegetarian diets 359
Eating disorders 360

16 Starvation: Metabolic Changes,
Survival and Death 363
Mechanisms for the regulation of the blood glucose
concentration 365
Metabolic responses to starvation 367
Sequence of metabolic changes from intermediate
starvation to death 372
Progressive decrease in protein degradation
in starvation 373
17 Defence Against Pathogens:
Barriers, Enzymes and
the Immune System 375
When the physical barrier is breached 375
The immune system 377
Adaptive immunity 380
Cytokines 390
Mechanisms for killing pathogens 391
Killing of intracellular bacteria and large parasites in
the extracellular fl uid 396
Allergy 398
Fuels and generation of ATP in immune cells:
consequences for a patient 400
Essential fatty acids and proliferation 402
The lymph nodes 402
Tolerance 404
Chronic infl ammation and autoimmunity 405
Immunosuppressive agents 406
Conditions that reduce the effectiveness
of the immune system 406
Factors that increase the effectiveness
of the immune system 407
Return of the ‘old’ infectious diseases 408
New infectious diseases 411
Defence in the intestine 415
18 Survival after Trauma:
Metabolic Changes and Response
of the Immune System 417
Physiological and metabolie responses the ebb &
fl ow phases 417
Nutrition 420
Mobilisation of triacylglycerol and protein in trauma 422
Metabolic changes in trauma and in starvation 423
Fever 424
Summary of the effects of trauma on the immune
system and the whole body 426

19 Sexual Reproduction 429
Male reproductive system 429
Female reproductive system 433
The menstrual cycle 434
Ovulation 435
Chemical communication in male and female
reproduction 436
Coitus and the sexual response in the male and female 440
Fertilisation 442
Pregnancy 444
Parturition 445
Contraception 446
The menopause 448
Sexually transmitted diseases 448
20 Growth and Death of Cells
and Humans: The Cell Cycle,
Apoptosis and Necrosis 451
Introduction to cell proliferation 451
The cell cycle 452
Death 477
21 Cancer: Genes, Cachexia and Death 485
Basic information 486
Oncogenes and proto-oncogenes 488
Proteins expressed by oncogenes 489
Processes by which proto-oncogenes can be activated
or converted to oncogenes 492
Tumour suppressor genes 493
Telomeres and telomerase in tumour cells 495
Metastasis 495
Metabolic changes in cancer patients 496
Overview of cancer 500
Cancer-causing agents or conditions 500
Chemotherapy 505
Radiotherapy 507
22 Atherosclerosis, Hypertension and
Heart Attack 509
Atherosclerosis 509
Hypertension 521
Heart attack (myocardial infarction) 524
Index 529



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