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Table of Contents


	Preface	xi
	List of Contributors	xiii
	Dedication	xvii
	Acknowledgments	xix
	Abbreviations	xxi
1	Introduction J W Baynes and M H Dominiczak	1
	Biochemistry and Clinical Medicine	1
	Entire Biochemistry on Two Pages	1
	The Final Word	3
2	Amino Acids and Proteins N Taniguchi	5
	Introduction	5
	Amino Acids	5
	Buffers	10
	Peptides and Proteins	11
	Purification and Characterization of Proteins	14
	Analysis of Protein Structure	17
3	Carbohydrates and Lipids J W Baynes	23
	Introduction	23
	Carbohydrates	23
	Lipids	26
	Structure of Biomembranes	29
4	Blood: Cells and Plasma Proteins W D Fraser	33
	Introduction	33
	Plasma and Serum	33
	Formed Elements of Blood	33
	Plasma Proteins	34
	The Acute Phase Response and C-Reactive Protein	40
5	Oxygen Transport G M Helmkamp	43
	Introduction	43
	Characteristics of Mammalian Globin Proteins	43
	Allosteric Modulation of the Oxygen Affinity of Hemoglobin	49
	Selected Topics	52
6	Catalytic Proteins � Enzymes J Fujii	59
	Introduction	59
	Enzymatic Reactions	59
	Enzyme Kinetics	62
	Mechanism of Enzyme Action	64
	Enzyme Inhibition	65
	Regulation of Enzyme Activity	68
	Enzymatic Measurement of Blood Glucose	70
7	Hemostasis and Thrombosis G Lowe	73
	Introduction	73
	Hemostasis	73
	The Vessel Wall	75
	Prostacyclin and Nitric Oxide	75
	Platelets	76
	Coagulation	78
	Fibrinolysis	83
8	Membranes and Transport M Maeda	87
	Introduction	87
	Types of Transport Processes	87
9	Bioenergetics and Oxidative Metabolism L W Stillway	97
	Introduction	97
	Oxidation as a Source of Energy	97
	Free Energy	98
	Conservation of Energy by Coupling with Adenosine Triphosphate	99
	Mitochondrial Synthesis of Adenosine Triphosphate from Reduced Coenzymes	99
	The Mitochondrial Electron Transport System	101
	Transfer of Electrons from NADH into Mitochondria	104
	Synthesis of Adenosine Triphosphate � The Chemiosmotic Hypothesis	107
	Inhibitors of Oxidative Metabolism	111
	Regulation of Oxidative Phosphorylation	113
10	Function of the Gastrointestinal Tract U V Kulkarni and I Broom	115
	Introduction	115
	The Gastrointestinal Tract	115
	Digestion	117
	Digestion and Absorption of Carbohydrates	118
	Digestion and Absorption of Lipids	121
	Digestion and Absorption of Proteins	124
11	Micronutrients: Vitamins and Minerals M H Dominiczak and I Broom	129
	Introduction	129
	Fat-Soluble Vitamins	129
	Water-Soluble Vitamins	133
	Trace Elements	140
12	Anaerobic Metabolism of Glucose in the Red Blood Cell J W Baynes	143
	Introduction	143
	The Erythrocyte	143
	Glycolysis	144
	Synthesis of 2,3-Bisphosphoglycerate	150
	The Pentose Phosphate Pathway	150
13	Carbohydrate Storage and Synthesis in Liver and Muscle J W Baynes	155
	Introduction	155
	Structure of Glycogen	156
	Pathway of Glycogenesis from Blood Glucose in Liver	156
	Pathway of Glycogenolysis in Liver	157
	Hormonal Regulation of Hepatic Glycogenolysis	158
	Mechanism of Action of Glucagon	158
	Mobilization of Hepatic Glycogen by Epinephrine	161
	Glycogenolysis in Muscle	163
	Regulation of Glycogenesis	164
	Gluconeogenesis	165
14	The Tricarboxylic Acid Cycle L W Stillway	173
	Introduction	173
	Functions of the Tricarboxylic Acid Cycle	173
	Pyruvate Carboxylase	175
	The Pyruvate Dehydrogenase Complex	175
	Enzymes and Reactions of the Tricarboxylic Acid Cycle	177
	Energy Yield from the Tricarboxylic Acid Cycle	182
	Regulation of the Tricarboxylic Acid Cycle	183
	Anaplerotic (�Building Up�) Reactions	183
15	Oxidative Metabolism of Lipids in Liver and Muscle J W Baynes	185
	Introduction	185
	Activation of Fatty Acids for Transport into the Mitochondrion	185
	Oxidation of Fatty Acids	186
	Ketogenesis � A Metabolic Pathway Unique to Liver	189
16	Biosynthesis and Storage of Fatty Acids U V Kulkarni and I Broom	195
	Introduction	195
	Fatty Acid Synthesis	195
	Fatty Acid Elongation	199
	Desaturation of Fatty Acids	199
	Essential Fatty Acids	200
	Storage and Transport of Fatty Acids: the Synthesis of Triacylglycerols	200
	Regulation of Total Body Fat Stores	201
17	Biosynthesis of Cholesterol and Steroids M H Dominiczak and A M Wallace	205
	Introduction	205
	Structure of Cholesterol	206
	Free and Esterified Cholesterol	206
	Intestinal Absorption of Cholesterol	206
	Biosynthesis of Cholesterol	206
	Bile Acids	211
	Steroid Hormones	214
	Vitamin D₃	216
18	Lipoproteins and Lipid Transport M H Dominiczak	219
	Introduction	219
	Lipoproteins	219
	Lipoprotein Receptors	221
	Enzymes and Transfer Proteins that Participate in Lipoprotein Metabolism	222
	Pathways of Lipoprotein Metabolism	222
	Dyslipidemias	225
	Atherogenesis	226
	Assessment of Cardiovascular Risk	232
	Clinical Management of Dyslipidemias	234
19	Biosynthesis and Degradation of Amino Acids Allen B Rawitch	237
	Introduction	237
	Metabolism of Dietary and Endogenous Proteins	237
	Amino Acid Degradation	239
	Metabolism of the Carbon Skeletons of Amino Acids	245
	Biosynthesis of Amino Acids	247
	Inherited Diseases of Amino Add Metabolism	248
20	Muscle: Energy Metabolism and Contraction J A Carson and J W Baynes	253
	Introduction	253
	Muscle Structure	254
	The Contractile Process	257
	Muscle Energy Metabolism	259
	Development and Regeneration of Muscle	261
21	Glucose Homeostasis and Fuel Metabolism M H Dominiczak	265
	Glucose Homeostasis	266
	Insulin	266
	Hypoglycemia	274
	Feed�Fast Cycle	274
	Metabolism during Stress	278
	Diabetes Mellitus	279
	Laboratory Assessment of Fuel Metabolism and Diabetes Mellitus	284
	Treating Diabetes	287
22	Nutrition and Energy Balance M H Dominiczak	291
	Introduction	291
	Regulation of Food Intake	291
	Regulation of Energy Balance	292
	Definitions in Nutrition Science	294
	Nutrigenomics	295
	Main Classes of Nutrients	296
	Essential (Limiting) Nutrients	298
	Minerals	298
	Nutritional Assessment	299
	Malnutrition	301
	Obesity	302
	Diet in Health and Disease	303
	Nutrition and Chronic Disease	305
23	Water and Electrolyte Homeostasis M H Dominiczak and M Szczepanska-Konkel	307
	Introduction	307
	Water	307
	Osmolality	310
	Kidneys	312
	Assessment of Renal Function	316
	Potassium	317
	Renin-Angiotensin System	317
	Integration of Water and Sodium Homeostasis	322
24	Regulation of Hydrogen Ion Concentration (Acid-Base Balance) M H Dominiczak and M Szczepanska-Konkel	325
	The Body Buffer Systems	325
	Lungs: the Gas Exchange	328
	Handling of Bicarbonate by the Kidneys	331
	Disorders of the Acid�Base Balance	332
25	Calcium and Bone Metabolism W D Fraser and M H Dominiczak	337
	Bone Structure and Bone Remodelling	337
	Calcium Metabolism	339
	Disorders of Calcium and Bone Metabolism	343
	Metabolic Bone Disease	347
26	Complex Carbohydrates: Glycoproteins A D Elbein	351
	Introduction	351
	Structures and Linkages	351
	Interconversions of Dietary Sugars	355
	Other Pathways of Sugar Nucleotide Metabolism	358
	Biosynthesis of Oligosaccharides	360
	Functions of the Oligosaccharide Chains of Glycoproteins	363
27	Complex Lipids A D Elbein	367
	Introduction	367
	Synthesis and Turnover of Glycerophospholipids	367
	Sphingolipids	370
	Lysosomal Storage Diseases Resulting from Defects in Glycolipid Degradation	372
	ABO Blood Group Antigens	374
	Other Blood Group Substances	374
28	The Extracellular Matrix G P Kaushal, A D Elbein and W M Carver	377
	Introduction	377
	Collagens	377
	Noncollagenous Proteins in the Extracellular Matrix	381
	Proteoglycans	384
29	Role of the Liver in Metabolism A F Jones	389
	Introduction	389
	Structure of the Liver	389
	Liver and Carbohydrate Metabolism	391
	Liver and Protein Metabolism	391
	Hemesynthesis	393
	Bilirubin Metabolism	393
	Drug Metabolism	395
	Pharmacogenomics	398
	Genomics of Liver Disease	399
	Biochemical Tests of Liver Function	399
	Classification of Liver Disorders	400
30	Biosynthesis and Degradation of Nucleotides A Gugliucci and R Thornburg	403
	Introduction	403
	Purine Metabolism	403
	Pyrimidine Metabolism	408
	Formation of Deoxynucleotides	409
31	Deoxyribonucleic Acid R Thornburg and A Gugliucci	413
	Introduction	413
	Structure of Deoxyribonucleic Acid	413
	The Cell Cycle in Eukaryotes	416
	DNA Repair	419
32	Ribonucleic Acid G A Bannon and R Thornburg	423
	Molecular Anatomy of Ribonucleic Acid Molecules	424
	Ribonucleic Acid Polymerases	426
	Messenger Ribonucleic Acid: Transcription	426
	Posttranscriptional Processing of Ribonucleic Acids	428
	Selective Degradation or Inactivation of Ribonucleic Acid	432
33	Protein Synthesis and Turnover J R Patton and G A Bannon	435
	Introduction	435
	The Genetic Code	435
	The Machinery of Protein Synthesis	436
	The Process of Protein Synthesis	439
	Protein Folding	441
	Protein Targeting and Posttranslational Modifications	442
34	Regulation of Gene Expression J R Patton, D M Hunt and A Jamieson	447
	Introduction	447
	Basic Mechanisms of Gene Expression	447
	Steroid Receptors	452
	Alternative Approaches to Gene Regulation in Humans	454
	The Human Genome Project	458
35	Recombinant DNA Technology W S Kistler, R G Best and A Jamieson	461
	Introduction	461
	Hybridization	461
	Deoxyribonucleic Acid Amplification and Cloning	467
	Specific Methods Used in the Analysis of Deoxyribonucleic Acid	472
	Deoxyribonucleic Acid Sequencing	477
36	Genomics, Proteomics and Metabolomics A Pitt and W Kolch	481
	Introduction	481
	Genomics	482
	Proteomics	490
	Metabolomics	494
37	Oxygen and Life J W Baynes	499
	Introduction	499
	The Inertness of Oxygen	499
	Reactive Oxygen Species and Oxidative Stress	500
	Reactive Nitrogen Species	502
	The Nature of Oxygen Radical Damage	502
	Antioxidant Defenses	503
	The Beneficial Effects of Reactive Oxygen Species	505
38	The Immune Response J A Grade and A Farrell	509
	Introduction	509
	Innate Immune Response	509
	Adaptive Immune Response	512
	Lymphocytes	513
	Molecules Involved in Antigen Recognition	513
	Major Histocompatibility Complex	514
	Lymphoid Tissues	515
	Antigen-Presenting Cells	516
	Reaction With, the Response to and the Elimination of Antigens	517
	T Cell Response	518
	Humoral Specific Immune Response	519
	Vaccination	520
39	Biochemical Endocrinology R K Simple and F F Bolander Jr	525
	Introduction	525
	Hormones	525
	Principles of Hormone Action	526
	Biochemical Assessment of Hormone Action	529
	Major Types of Endocrine Pathology	529
	The Hypothalamo�Pituitary Regulatory System	531
	The Hypothalamo�Pituitary�Thyroid Axis	532
	The Hypothalamo�Pituitary�Adrenal Axis	536
	The Hypothalamo�Pituitary�Gonadal Axis	540
	The Growth Hormone Axis	545
	The Prolactin Axis	547
40	Membrane Receptors and Signal Transduction M M Harnett and H S Goodridge	551
	Introduction	551
	Hormone Receptors	551
	Receptor Coupling to Intracellular Signal Transduction	553
	Second Messengers	554
41	Neurochemistry E J Thompson	569
	Introduction	569
	Brain and Peripheral Nerve	569
	Cells of the Nervous System	570
	Synaptic Transmission	572
	The Mechanism of Vision	575
42	Neurotransmitters S Heals	579
	Introduction	579
	Definition of a Neurotransmitter	579
	Classification of Neurotransmitters	579
	Neurotransmission	580
	Classes of Neurotransmitters	583
43	Cellular Homeostasis: Cell Growth, Differentiation and Cancer M M Harnett and H S Goodridge	593
	Introduction	593
	The Cell Cycle	593
	Growth Factors	594
	Regulation of the Cell Cycle	597
	Apoptosis	600
	Cancer	603
44	Aging J W Baynes	609
	Introduction	609
	Theories of Aging	611
	Genetic Models of Increased Lifespan	615
	Anti-Aging Interventions � What Works and What Doesn�t	617
Appendix	Selected Clinical Laboratory Reference Ranges Yee Ping Teoh and M H Dominiczak	621
	Index	629