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CONTENTS
Preface ... xiii
Authors ... xv
1. Introduction / Victor W. Rodwell, PhD ... 1
The Elements of The Second & Third Periods of the Periodic Table ... 1
Review of Organic Chemistry ... ...
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CONTENTS
Preface ... xiii
Authors ... xv
1. Introduction / Victor W. Rodwell, PhD ... 1
The Elements of The Second & Third Periods of the Periodic Table ... 1
Review of Organic Chemistry ... 2
Functional Groups Important in Physiologic Chemistry ... 8
2. Water / Victor W. Rodwell, PhD ... 11
Introduction ... 11
Molecular Structure of Water ... 11
Macromolecufar Structure of Water ... 11
Hydrogen Bonds ... 12
Dissociation of Water ... 12
The Concept of pH ... 13
Protonic Equilibria of Functional Groups That Are Weak Acids or Bases ... 14
The Henderson-Hasselbalch Equation ... 16
Buffers & Buffering ... 17
3. Amino Acids & Peptides / Victor W. Rodwell, PhD ... 18
Introduction ... 18
Amino Acids ... 18
Protonic Equilibria of Amino Acids ... 18
Structures of Amino Acids ... 20
Optical Isomers of Amino Acids ... 20
Physical Properties of Amino Acids ... 25
Chemical Reactions of Amino Acids ... 25
Peptides ... 28
Determination of the Primary Structure of Peptides ... 30
Technics Used in Determining Primary Peptide Structures ... 33
Conformation of Peptides in Solution ... 34
Synthesis of Peplides ... 34
Physiologically Active Peptides ... 35
4. Proteins / Victor W. Rodwell, PhD ... 37
Classification of Proteins ... 37
Size & Shape of Proteins ... 38
Bonds Responsible for Protein Structure ... 38
Orders of Protein Structure ... 39
Primary Structure of Proteins ... 41
Secondary & Tertiary Structure of Proteins ... 43
Quaternary Structure of Proteins ... 45
Denaturation of Proteins ... 46
Color Reactions of Proteins ... 47
5. General Properties of Enzymes / Victor W. Rodwell, PhD ... 48
Catalysis ... 48
Coenzymes ... 48
Enzyme Specificity ... 50
Enzyme Classification & Nomenclature ... 51
Quantitative Measurement of Enzyme Activity ... 53
Isolation of Enzymes ... 54
Intracellular Distribution of Enzymes ... 55
6. Kinetic Properties of Enzymes / Victor W. Rodwell, PhD ... 60
Kinetic Theory of Reaction ... 60
Effect of Reactant Concentration ... 61
Inhibition of Enzyme Activity ... 67
The Catalytic Site ... 70
Mechanism of Enzyme Action ... 74
Isozymes ... 77
Enzymes in Clinical Diagnosis ... 78
7. Regulation of Enzyme Activity / Victor W. Rodwell, PhD ... 82
Physiologic Role of Metabolic Regulation ... 82
Available Options for Regulation of Enzymes ... 83
Regulation of Enzyme Quantity ... 83
Regulation of the Catalytic Efficiency of Enzymes ... 88
Regulation of Catalytic Efficiency : Availability of Reactants ... 89
Regulation of Catalytic Efficiency : Feedback Inhibition ... 90
Regulation of Catalytic Efficiency : Covalent Modification ... 95
8. Carbohydrates / Peter A. Mayes, PhD, DSc ... 97
Monosaccharides ... 98
Hexoses ... 100
Glycosides ... 100
Important Chemical Reactions of Monosaccharides ... 101
Deoxy Sugars ... 105
Amino Sugars (Hexosamines) ... 105
Disaccharides ... 105
Polysaccharides ... 105
Carbohydrates of Cell Membranes ... 110
Tests for Carbohydrates ... 110
9. Lipids / Peter A. Mayes, PhD, DSc ... 112
Fatty Acids ... 112
Triacylglycerols (Triglycerides) ... 114
Phospholipids ... 115
Cerebrosides (Glycolipids) ... 117
Steroids ... 118
The Plasma Lipoproteins ... 119
Characteristic Chemical Reactions & Properties of Lipids ... 121
The Cell Membranes ... 123
10. Nucieotides / David W. Martin, Jr. MD ... 126
Nucleosides & Nucleotides ... 128
Naturally Occurring Nucleotides ... 131
Synthetic Derivatives ... 133
11. Nucleic Acids &, Chromatin / David W. Martin, Jr. MD ... 135
12. The Fat-Soluble Vitamins / Harold A. Harper, PhD ... 147
Vitamin A ... 147
The Vitamins D ... 151
The Vitamins E ... 153
The Vitamins K ... 156
13. The Water-Soluble Vitamins / Harold A. Harper, PhD ... 159
Vitamin C (Ascorbic Acid) ... 159
The Vitamins of the B Complex ... 161
Thiamin ... 161
Riboflavin ... 162
Niacin & Niacinamide ... 163
Pyridoxine ... 165
Pantothenic Acid ... 169
Lipoic Acid ... 170
Biotin ... 171
The Folic Acid Group ... 172
Inositol ... 178
Para-aminobenzoic Acid ... 178
Vitamin B1 2 ... 178
Choline ... 184
14. The Blood, Lymph, & Cerebrospinal Fluid / Harold A. Harper, PhD ... 188
Blood ... 188
The Clotting of Blood ... 189
The Plasma Proteins ... 194
Hemoglobin ... 201
Metabolic Characteristics of the Erythrocyte ... 210
The Anemias ... 213
Blood Chemistry ... 213
Lymph ... 215
Cerebrospinal Fluid ... 216
15. The Chemistry of Respiration / David W. Martin, Jr. MD ... 217
Chemical & Physiologic Events Affecting Diffusion of Oxygen & Carbon Dioxide ... 217
Transport of Oxygen in Blood ... 220
Transport of C O2 in Blood ... 222
Respiratory Regulation of Acid-Base Balance ... 224
16. Porphyrins & Bile Pigments / David W. Martin, Jr. MD ... 228
17. Digestion & Absorption From the Gastrointestinal Tract / Peter A. Mayes, PhD, DSc ... 245
Digestion in the Mouth ... 245
Digestion in the Stomach ... 245
Pancreatic & Intestinal Digestion ... 246
The Bile ... 250
Intestinal Putrefaction & Fermentation ... 253
Absorption From the Gastrointestinal Tract ... 254
18. Bioenergetics / Peter A. Mayes, PhD, DSc ... 260
Introduction ... 260
Role of High-Energy Phosphates in Bioenergetics & Energy Capture ... 262
19. Biologic Oxidation / Peter A. Mayes, PhD, DSc ... 266
Enzymes & Coenzymes Involved in Oxidation, & Reduction ... 267
The Respiratory Chain ... 272
The Role of the Respiratory Chain in Energy Capture ... 274
Mechanisms of Oxidative Phosphorylation ... 276
The Chemical Hypothesis ... 276
The Chemiosmotic Hypothesis ... 279
20. The Citric Acid Cycle-The Catabolism of Acetyl-CoA / Peter A. Mayes, PhD, DSc ... 285
21. Metabolism of Carbohydrate / Peter A. Mayes, PhD, DSc ... 294
Intermediary Metabolism of Carbohydrate ... 294
Glycolysis ... 295
Oxidation of Pyruvale to Acetyl-CoA ... 299
Glycogen Formation & Degradation ... 299
Glycogenesis ... 301
Glycogenolysis ... 304
The Hexose Monophosphate Shunt or Pentose Phosphate Pathway ... 307
Gluconeogenesis ... 311
Metabolism of Hexoses ... 314
Other Pathways of Glucose Metabolism ... 314
The Uronie Acid Pathway ... 314
Metabolism of Fructose ... 314
Metabolism of Galactose ... 317
22. Metabolism of Lipids : I. Fatty Acids / Peter A. Mayes, PhD, DSc ... 321
Oxidation of Fatty Acids ... 322
Biosynthesis of Saturated Fatty Acids ... 327
Metabolism of Unsaturated Fatty Acids ... 330
The Essential Fatty Acids ... 333
The Essential Fatty Acids ... 333
Metabolism of Acylglycerols ... 335
Metabolism of Sphingolipids ... 339
Phospholipids & Sphingolipids in Disease (Lipidoses) ... 341
23. Metabolism of Lipids : II. Role of Tissues / Peter A. Mayes, PhD, DSc ... 343
Metabolism of Adipose Tissue & the Mobilization of Fat ... 344
Metabolism of the Plasma Lipoproteins ... 348
Role of the Liver in Lipid Metabolism ... 353
Ketosis ... 356
Cholesterol Metabolism ... 359
24. Regulation of Carbohydrate & Lipid Metabolism / Peter A. Mayes, PhD, DSc ... 367
General Principles of Regulation of Metabolic Pathways ... 367
Identification of Nonequilibrium Reactions & Regulatory Enzymes ... 367
Metabolic Control of an Enzyme-Catalyzed Reaction ... 368
Regulation of Carbohydrate Metabolism ... 368
Regulation of Carbohydrate Metabolism at the Cellular & Enzymatic Level ... 368
The Blood Glucose ... 373
Regulation of Lipid Metabolism ... 376
Regulation of Kelogenesis ... 378
Interconversion of Major Foodsluffs ... 381
The Economics of Carbohydrate & Lipid Metabolism in the Whole Body ... 382
25. Biosynthesis of Amino Acids / Victor W. Rodwell, PhD ... 384
Amino Acid Metabolism ... 384
Nutritionally Essential & Nutritionally Nonessential Amino Acids ... 384
Nutritionally Nonessential Amino Acids ... 385
Nutritionally Nonessential Amino Acids Formed From Amphibolic Intermediates ... 385
Nutritionally Nonessenlial Amino Acids Formed From Other Nutritionally Nonessential Amino Acids ... 389
Nutritionally Nonessenlial Amino Acids Formed From Nutritionally Essential Amino Acids ... 392
Nutritionally Essential Amino Acids ... 392
Biosynthesis of Nutritionally Essential Amino Acids From Glutamate ... 392
Biosynthesis of Nutritionally Essential Amino Acids From Aspartate ... 393
Biosynthesis of Nutritionally Essential Amino Acids From Amphibolic Intermediates ... 394
26. Catabolism of Amino Acid Nitrogen / Victor W. Rodwell, PhD ... 397
Overall View ... 397
Transamination ... 397
Oxidative Deaminaiion ... 399
L-Glutamate Dehydrogenase ... 399
Formation of Ammonia ... 400
Transport of Ammonia ... 400
Circadian Changes in Plasma Amino Acid Levels ... 401
Urea Synthesis ... 401
Regulation of Urea Synthesis ... 403
Metabolic Disorders Involving the Urea Cycle ... 404
27. Catabolism of the Carbon Skeletons of Amino Acids / Victor W. Rodwell, PhD ... 406
Conversion of Carbon Skeletons of Common L-a-Amino Acids to Amphibolic Intermediates ... 406
Amino Acids Forming Oxaloacetate ... 407
Amino Acids Forming α-Ketoglutarate ... 407
Amino Acids Forming Pyruvate ... 409
Amino Acids Forming Acetyl-Coenzyme A ... 411
Amino Acids Forming Succinyl-Coenzyme A ... 418
Metabolic Defects in Amino Acid Metabolism ... 423
28. Conversion of Amino Acids to Specialized Products / Victor W. Rodwell, PhD ... 430
Glycine ... 430
Alanine ... 431
Serine ... 431
Threonine ... 432
Methionine ... 432
Cysteine ... 433
Arginine ... 433
Histidine ... 434
Tryptophan ... 434
Phenylalanine & Tyrosine ... 437
Metabolism of Creatine & Creatinine ... 437
29. Metabolism of Purine & Pyrimidine Nucleotides / David W. Martin, Jr. MD ... 440
30. Metabolism of Nucleic Acids / David W. Martin, Jr. MD ... 460
The Nature of DNA ... 460
Genetic Organization of the Mammalian Genome ... 462
DNA Metabolism ... 465
Alteration & Rearrangement of Genetic Material ... 470
Biologic Function of Ribonucleic Acid (RNA) ... 473
RNA Metabolism ... 474
Inhibitors of DNA & RNA Synthesis ... 480
Nucleases ... 480
31. Protein Synthesis & the Genetic Code / David W. Martin, Jr. MD ... 481
32. Regulation of Gene Expression / David W. Martin, Jr. MD ... 497
33. General Characteristics of Hormones / Gerold M. Grodsky, PhD ... 505
34. Chemistry & Functions of the Hormones : Ⅰ. Thyroid, Pancreas, Adrenal, & Gastrointestinal Tract / Gerold M. Grodsky, PhD ... 511
The Thyroid ... 511
The Parathyroids ... 517
The Pancreas ... 519
Insulin ... 519
Glucagon ... 529
Somatostatin ... 530
The Adrenals ... 531
The Adrenal Medulla ... 531
The Adrenal Cortex ... 535
The Organs Producing Sex Hormones ... 546
Male Hormones ... 547
Female Hormones ... 548
The Gastrointestinal Hormones ... 552
35. Chemistry & Functions of the Hormones : Ⅱ. Pituitary & Hypothalamus / Gerold M. Grodsky, PhD ... 556
36. Water & Mineral Metabolism / David D. Tyier, MA, PhD ... 569
Water Metabolism ... 569
Mineral Metabolism ... 574
Calcium ... 575
Phosphorus ... 577
Magresium ... 578
Sodium ... 579
Potassium ... 581
The Sodium-Potassium Pump ... 582
Lithium ... 583
Chlorine ... 583
Sulfur ... 584
Trace Elements ... 584
Essential Trace Elements ... 584
Iron ... 584
Copper ... 588
Iodine ... 589
Manganese ... 589
Cobalt ... 590
Zinc ... 590
Fluorine ... 591
Molybdenum ... 592
Selenium ... 592
Chromium ... 593
Possibly Essential Trace Elements ... 593
Nonessential Trace Elements ... 594
Aluminum ... 594
Boron ... 594
Cadmium ... 594
Other Nonessenlial Trace Elements ... 594
37. Calorimetry : Elements of Nutrition / Harold A. Harper, PhD ... 596
Basal Metabolism ... 598
Measurement of Energy Requirements ... 599
Specific Dynamic Action (SDA) ... 600
The Elements of Nutrition ... 600
Recommended Dietary Allowances ... 609
38. Immunochemistry / Kent R. Cochrum, DVM ... 613
Structure of Immunoglobulins ... 614
Electrophoretic Determination of Immunoglobulins ... 616
Quantitaiive Immunoglobulin Determinations (Radial Diffusion Technic) ... 619
Antigens ... 620
Antigenic Determinants ... 621
Immunopotency ... 624
39. The Kidney &. the Urine / John David Wallin, MD ... 626
Formation of Urine ... 626
Acidification of the Urine ... 637
Abnormalities of Acid-Base Regulation by the Kidney ... 638
Mechanism of Action of Diuretics ... 640
Tests of Renal Function ... 640
Composition of Urine ... 642
Hormones of the Kidney ... 646
40. Muscle Tissue / Harold A. Harper, PhD ... 650
Muscle Structure ... 650
The Proteins in Muscle ... 651
Molecular Events in Muscle Contraction ... 653
Muscle Metabolism ... 654
Muscle Phosphagens ... 655
Inorganic Constituents of Muscle ... 656
41. Epithelial, Connective, & Nerve Tissues / Harold A. Harper, PhD ... 657
Epithelial Tissue ... 657
Connective Tissue ... 657
Nerve Tissue ... 663
Abbreviations Encountered in Physiologic Chemistry ... 667
Index ... 669
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