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