Preface 1. Introduction / Vivtor 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 / Vivtor W.Rodwell, PhD ... 12 Introduction ... 12 Molecular Structure of Water ... 12 Macromolecular Structure of Water ... 12 Hydrogen Bonds ... 13 Dissociation of Water ... 13 The Concept of pH ... 14 Protonic Equilibria of Functional Groups That Are Weak Acids or Bases ... 15 The Henderson-Hasselbalch Equation ... 17 Buffers & Buffering ... 18 3. Amino Acids & Peptides / Vivtor W.Rodwell, PhD ... 20 Introduction ... 20 Amino Acids ... 20 Protonic Equilibria of Amino Acids ... 20 Structures of Amino Acids ... 22 Optical Isomers of Amino Acids ... 27 Physical Properties of Amino Acids ... 27 Chemical Reactions of Amino Acids ... 28 Peptides ... 30 Determination of the Primary Structure of Peptides ... 32 Technics Used in Determining Primary Peptide Structures ... 36 Conformation of Peptides in Solution ... 37 Synthesis of Peptides ... 37 Physiologically Active Peptides ... 38 4. Proteins / Vivtor W.Rodwell, PhD ... 40 Classification of Proteins ... 40 Size & Shape of Proteins ... 41 Bonds Responsible for Protein Structure ... 42 Orders of Protein Structure ... 43 Primary Structure of Proteins ... 45 Secondary & Tertiary Structure of Proteins ... 47 Quaternary Structure of Proteins ... 50 Denaturation of Proteins ... 51 Color Reactions of Proteins ... 51 5. General Properties of Enzymes / Vivtor W.Rodwell, PhD ... 52 Catalysis ... 52 Coenzymes ... 52 Enzyme Specificity ... 54 Enzyme Classification & Nomenclature ... 56 Quantitative Measurement of Enzyme Activity ... 58 Isolation of Enzymes ... 58 Intracellular Distribution of Enzymes ... 60 6. Kinetic Properties of Enzymes / Vivtor W.Rodwell, PhD ... 65 Kinetic Theory of Reaction ... 65 Effect of Reactant Concentration ... 66 Inhibition of Enzyme Activity ... 72 The Catalytic Site ... 76 Mechanism of Enzyme Action ... 81 Isozymes ... 84 7. Regulation of Enzyme Activity / Vivtor W.Rodwell, PhD ... 87 Physiologic Role of Metabolic Regulation ... 87 Available Options for Regulation of Enzymes ... 88 Regulation of Enzyme Quantity ... 88 Regulation of the Catalytic Efficiency of Enzymes ... 94 Regulation of Catalytic Efficiency : Availability of Reactants ... 95 Regulation of Catalytic Efficiency : Feedback Inhibition ... 97 Regulation of Catalytic Efficiency : Covalent Modification ... 103 8. Carbohydrates / Peter A.Mayes, PhD, DSc ... 104 Monosaccharides ... 107 Hexoses ... 107 Glycosides ... 108 Important Chemical Reactions of Monosaccharides ... 109 Deoxy Sugars ... 112 Amino Sugars(Hexosamines) ... 113 Disaccharides ... 113 Polysaccharides ... 113 Carbohydrates of Cell Membranes ... 116 9. Lipids / Peter A.Mayes, PhD, DSc ... 119 Fatty Acids ... 119 Triacylglycerols(Triglycerides) ... 121 Phospholipids ... 123 Cerebrosides(Glycolipids) ... 124 Steroids ... 125 The Plasma Lipoproteins ... 127 Characteristic Chemical Reactions & Properties of Lipids ... 128 The Cell Membranes ... 133 10. Nucleotides / Davis W.Martin, Jr.,MD ... 134 Nucleosides & Nucleotides ... 136 Naturally Occurring Nucleotides ... 139 Synthetic Derivatives ... 141 11. Nucleic Acids & Chromatin / Davis W.Martin, Jr.,MD ... 143 12. The Fat-Soluble Vitamins / Harold A.Harper, PhD ... 156 Vitamin A ... 156 The Vitamins D ... 159 The Vitamins E ... 162 The Vitamins K ... 164 13. The Water-Soluble Vitamins / Harold A.Harper, PhD ... 167 Vitamin C(Ascorbic Acid) ... 167 The Vitamins of the B Complex ... 168 Thiamin ... 169 Riboflavin ... 170 Niacin & Niacinamide ... 171 Pyridoxine ... 173 Pantothenic Acid ... 176 Lipoic Acid ... 177 Biotin ... 178 The Folic Acid Group ... 180 Inositol ... 183 Para-aminobenzoic Acid ... 183 Vitamin B₁₂ ... 184 Choline ... 188 14. The Blood, Lymph, & Cerebrospinal Fluid / Harold A.Harper, PhD ... 192 Blood ... 192 The Clotting of Blood ... 193 The Plasma Proteins ... 199 Hemoglobin ... 207 Metabolic Characteristics of the Erythrocyte ... 218 Blood(cont'd) The Anemias ... 221 Blood Chemistry ... 223 Lymph ... 224 Cerebrospinal Fluid ... 224 15. The Chemistry of Respiration / David W. Martin, Jr., MD ... 225 Chemical & Physiologic Events Affecting Diffusion of Oxygen & Carbon Dioxide ... 225 Transport of Oxygen in Blood ... 229 Transport of CO₂ in Blood ... 231 Respiratory Regulation of Acid-Base Balance ... 233 16. Prophyrins & Bile Pigments / David W. Martin, Jr., MD ... 237 17. Digestion & Absorption From the Gastrointestinal Tract / Peter A. Mayes, PhD, DSc ... 256 Digestion in the Mouth ... 256 Digestion in the Stomach ... 256 Pancreatic & Intestinal Digestion ... 257 The Bile ... 261 Intestinal Putrefaction & Fermentation ... 265 Absorption From the Gastrointestinal Tract ... 266 18. Bioenergetics / Peter A. Mayes, PhD, DSc ... 272 Introduction ... 272 Role of High-Energy Phosphates in Bioenergetics & Energy Capture ... 274 19. Biologic Oxidation / Peter A. Mayes, PhD, DSc ... 278 Enzymes & Coenzymes Involved in Oxidation & Reduction ... 279 The Respiratory Chain ... 284 The Role of the Respiratory Chain in Energy Capture ... 287 Mechanisms of Oxidative Phosphorylation ... 289 The Chemical Hypothesis ... 289 The Chemiosmotic Hypothesis ... 293 20. The Citric Acid Cycle-The Catabolism of Acetyl-CoA / Peter A. Mayes, PhD, DSc ... 299 21. Metabolism of Carbohydrate / Peter A. Mayes, PhD, DSc ... 308 Intermediary Metabolism of Carbohyfrate ... 308 Glycolysis ... 309 Oxidation of Pyruvate to Acetyl-CoA ... 313 Glycogen Formation & Degradation ... 314 Glycogenesis ... 315 Glycogenolysis ... 319 The Hexose Monophosphate Shunt or Pentose Phosphate Pathway ... 321 Gluconeogenesis ... 324 Metabolism of Hexoses ... 328 Other Pathways of Glucose Metabolism ... 328 The Uronic Acid Pathway ... 328 Metabolism of Fructose ... 330 Metabolism of Galactose ... 332 22. Metabolism of Lipids : I. Fatty Acids / Peter A. Mayes, PhD, DSc ... 336 Oxidation of Fatty Acids ... 337 Biosynthesis of Saturated Fatty Acids ... 342 Metabolism of Unsaturated Fatty Acids ... 345 The Essential Fatty Acids ... 348 Metabolism of Acylglycerols ... 351 Metabolism of Sphingolipids ... 356 Phospholipids & Sphingolipids in Disease(Lipidoses) ... 358 23. Metabolism of Lipids : Ⅱ. Role of Tissues / Peter A. Mayes, PhD, DSc ... 359 Metabolism of Adipose Tissue & the Mobilization of Fat ... 360 Metabolism of the Plasma Lipoproteins ... 365 Role of the Liver in Lipid Metabolism ... 370 Ketosis ... 374 Cholesterol Metabolism ... 377 24. Regulation of Carbohydrate & Lipid Metabolism / Peter A. Mayes, PhD, DSc ... 384 General Principles of Regulation of Metabolic Pathways ... 384 Identification of Nonequilibrium Reactions & Regulatory Enzymes ... 384 Metabolic Control of an Enzyme-Catalyzed Reaction ... 385 Regulation of Carbohydrate Metabolism ... 385 Regulation of Carbohydrate Metabolism at the Cellular & Enzymatic Level ... 385 Regulation of Carbohydrate Metabolism(cont'd) The Blood Glucose ... 391 Regulation of Lipid Metabolism ... 394 Regulation of Ketogenesis ... 395 Interconversion of Major Foodstuffs ... 399 The Economics of Carbohydrate & Lipid Metabolism in the Whole Body ... 400 25. Biosynthesis of Amino Acids / Victor W. Rodwell, PhD ... 402 Amino Acid Metabolism ... 402 Nutritionally Essential & Nutritionally Nonessential Amino Acids ... 402 Nutritionally Nonessential Amino Acids ... 403 Nutritionally Nonessential Amino Acids Formed From Amphibolic Intermediates ... 403 Nutritionally Nonessential Amino Acids Formed From Other Nutritionally Nonessential Amino Acids ... 408 Nutritionally Nonessential Amino Acids Formed From Nutritionally Essential Amino Acids ... 410 Nutritionally Essential Amino Acids ... 411 Biosynthesis of Nutritionally Essential Amino Acids From Glutamate ... 411 Biosynthesis of Nutritionally Essential Amino Acids From Aspartate ... 412 Biosynthesis of Nutritionally Essential Amino Acids From Amphibolic Intermediates ... 413 26. Catabolism of Amino Acid Nitrogen / Victor W. Rodwell, PhD ... 416 Overall View ... 416 Transamination ... 416 Oxidative Deamination ... 418 L-Glutamate Dehydrogenase ... 418 Formation of Ammonia ... 419 Transport of Ammonia ... 419 Circadian Changes in Plasma Amino Acid Levels ... 421 Urea Synthesis ... 422 Regulation of Urea Synthesis ... 423 Metabolic Disorders Involving the Urea Cycle ... 423 27. Catabolism of the Carbon Skeletons of Amino Acids / Victor W. Rodwell, PhD ... 425 Conversion of Carbon Skeletons of Common L-α-Amino Acids to Amphibolic Intermediates ... 425 Amino Acids Forming Oxaloacetate ... 426 Amino Acids Forming α-Ketoglutarate ... 426 Amino Acids Forming Pyruvate ... 428 Amino Acids Forming Acetyl-Coenzyme A ... 430 Amino Acids Forming Succinyl-Coenzyme A ... 438 28. Conversion of Amino Acids to Specialized Products / Victor W. Rodwell, PhD ... 444 Glycine ... 444 Alanine ... 445 Serine ... 446 Threonine ... 446 Mrthionine ... 446 Cysteine ... 447 Arginine ... 447 Histidine ... 447 Tryptophan ... 449 Phenylalnine & Tyrosine ... 451 Metabolism of Creatine & Creatinine ... 452 29. Metabolism of Purine & Pyrimidine Nucleotides / David W. Martin, Jr., MD ... 455 30. Metabolism of Nucleic Acids / David W. Martin, Jr., MD ... 472 The Nature of DNA ... 472 Genetic Organization of the Mammalian Genome ... 474 DNA Metabolism ... 477 Alteration & Rearrangement of Genetic Meterial ... 482 Biologic Function of Ribonucleic Acid(RNA) ... 486 RNA Metabolism ... 486 Inhibitors of DNA & RNA Synthesis ... 493 Nucleases ... 493 31. Protein Synthesis & the Genetic Code / David W. Martin, Jr., MD ... 494 32. Regulation of Gene Expression / David W. Martin, Jr., MD ... 511 33. General Characteristics of Hormones / Gerold M. Grodsky, PhD ... 519 34. Chemistry & Functions of the Hormones : Ⅰ. Thyroid, Pancreas, Adrenal, & Gastrointestinal Tract / Gerold M. Grodsky, PhD ... 526 The Thyroid ... 526 The Parathyroids ... 531 The Pancreas ... 535 Insulin ... 535 Glucagon ... 546 Somatostatin ... 548 The Adrenals ... 548 The Adrenal Medulla ... 548 The Adrenal Cortex ... 553 The Organs Producing Sex Hormones ... 564 Male Hormones ... 564 Female Hormones ... 566 The Gastrointestinal Hoemones ... 569 35. Chemistry & Functions of the Hormones : Ⅱ. Pituitary & Hypothalamus / Gerold M. Grodsky, PhD ... 574 36. Water & Mineral Metabolism / Davis D. Tyler, MA, PhD ... 588 Water Metabolism ... 588 Mineral Metabolism ... 593 Calcium ... 594 Phosphorus ... 595 Magnesium ... 596 Sodium ... 597 Potassium ... 598 The Sodium-Potassium Pump ... 599 Lithium ... 600 Chlorine ... 600 Sulfur ... 601 Trace Elements ... 601 Essential Trace Elements ... 601 Iron ... 601 Copper ... 604 Trace Elements(cont'd) Iodine ... 606 Manganese ... 606 Cobalt ... 606 Zinc ... 607 Fluorine ... 608 Molybdenum ... 608 Selenium ... 608 Chromium ... 610 Possibly Essential Trace Elements ... 610 Nonessential Trace Elements ... 610 Aluminum ... 610 Boron ... 610 Cadmium ... 610 Other Nonessential Trace Elements ... 611 37. Calorimetry : Elements of Nutrition / Harold A. Harper, PhD ... 612 Basal Metabolism ... 614 Measurement of Energy Requirements ... 616 Specific Dynamic Action(SDA) ... 616 The Elements of Nutrition ... 617 38. Immunochemistry / Kent R. Cochrum, DVM ... 629 Structure of Immunoglobulins ... 630 Electrophretic Determination of Immunoglobulins ... 633 Quantitative Immunoglobulin Determinations(Radial Diffusion Technic) ... 635 Antigens ... 636 Antigenic Determinants ... 638 Immunopotency ... 640 39. The Kidney & the Urine / John David Wallin, MD ... 642 Formation of Urine ... 642 Acidification of the Urine ... 654 Abnormalities of Acid-Base Regulation by the Kidney ... 655 Mechanism of Action of Diuretics ... 657 Tests of Renal Function ... 658 Composition of Urine ... 660 Hormones of the Kidney ... 664 40. Muscle Tissue / Harold A. Harper, PhD ... 669 Muscle Structure ... 669 The Proteins in Muscle ... 670 Molecular Events in Muscle Contraction ... 673 Muscle Metabolism ... 673 Muscle Phosphagens ... 674 Inorganic Constituents of Muscle ... 675 41. Epithelial, Connective, & Nerve Tissues / Harold A. Harper, PhD ... 676 Epithelial Tissue ... 676 Connective Tissue ... 676 Nerve Tissue ... 684 Abbreviations Encountered in Physiologic Chemistry ... 689