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BK

Second edition

London ; San Diego ; Cambridge ; Oxford : Elsevier : Academic Press, [2022]

xvii, 863 stran : ilustrace (převážně barevné) ; 29 cm

ISBN 978-0-323-85718-5 (vázáno)

Obsahuje bibliografie a rejstřík

002002137

About the author // Preface // Introduction // 1. Organ Systems and Tissues 1 // Treatment of the Injured Knee: Use of // Stem Cells to Replace Damaged Cartilage 1 // Development of Organs 3 // Stem Cells 4 // Gross Structures and Functions of Organ // Systems 6 // Skin 6 // The Skeleton 8 // Cellular Composition of Tissues 13 // Summary 18 // Suggested Reading 19 // Multiple-Choice Questions 20 // 2. The Cell 23 // Cellular Trafficking in Alzheimer’s Disease 23 // The Effects of Amyloid Beta (Ap) on Synapse Function 26 // Cell Membrane 27 // Nucleus and Cell Division 28 // Cytoplasm and Cytoskeleton 32 // Endoplasmic Reticulum 35 // Golgi Apparatus 35 // Mitochondria 38 // Peroxisome 39 // Lysosome 40 // Summary 41 // Suggested Reading 42 // Multiple-Choice Questions 42 // 3. Introductory Discussion on Water, pH, Buffers, and General Features of // Receptors, Channels, and Pumps 45 // Diabetes Insipidus 45 // Thirst and Arginine Vasopressin 47 // Action of Arginine Vasopressin on the Distal // Kidney Tubule 48 // Water and Biological Roles 48 // The Photocatalytic Dissociation of the // Water Molecule Into Its Gaseous Atoms 49 // Water Channels: Aquaporins 51 // The Role of Water in Protein Folding 53 // Protein-Water Interactions in Enzymatic Reactions 56 // Metabolic Water 57 // Proton Transfer in Liquid Water 57 // The Concentration of Hydrogen Ions // (Protons) in Solution (pH) 58 // Buffers 59 // Receptors 63 // Ion Channels 65 // Enzymatic Pumping Mechanism 66 // Summary 66 // Suggested Reading 68 // Multiple-Choice Questions 69 // Proteins // 71 // Prion Disease, A Disease of Protein // Conformational Change 71 // Actions of Cellular Prion (PrP°) 73 // Binding to Amyloid Proteins 73 // Copper Binding to Cellular Prion Protein 73 // PrPc and Differentiation and Function of // Adipocytes 75 // Amino Acids 76 // Amino Acid-Related Diseases 76 //

Biochemistry of the Amino Acids 79 // Amino Acids Have Two or More Potential // Charges 83 // Numbering of Carbons in Amino Acids 83 // Charge State 83 // Synthesis of Nonessential Amino Acids and Amino Acid Degradation 85 // Proteins 88 // Amino Acid Sequence 89 // Secondary, Tertiary, and Quaternary Structures 89 // Protein Folding 91 // Protein Degradation 94 // Protein Classification 94 // Proteomics 95 // Protein Microarray 98 // Summary 100 // Cryo-Electron Microscopy at Near-Atomic // Resolution of Proteins and Macromolecular Complexes Without the Need for Crystals 102 // Suggested Reading 105 // Multiple-Choice Questions 106 // 5. Enzymes 109 // Diagnostic Enzymology 109 // Enzymes With Multiple Subunits: // Tissue-Specific Isozymes 109 // General Aspects of Catalysis 111 // Lineweaver—Burk Equation 114 // Michaelis—Menten Equation 115 // Inhibition of Enzymatic Activity 116 // Allosterism—Non-Michaelis—Menten Kinetics 123 // Classification 125 // Coenzymes 127 // Prosthetic Groups 134 // Enzyme Filamentation in Cellular Regulation 136 // Drugs That Operate as Enzyme Inhibitors 137 // Drug Resistance 138 // Rational Drug Design 141 // Enzyme Replacement Therapy —Gaucher // Disease 141 // Summary 143 // Suggested Reading 144 // Multiple-Choice Questions 145 // 6. Insulin and Sugars 147 // Diabetes 147 // Insulin 152 // The Pancreatic (3-Cell and Insulin Secretion 154 // Detrimental Effects of Diabetes 156 // Synthetic Sweeteners 156 // Chemistry of Simple Sugars 158 // Glucose Transport 162 // Pentose Phosphate Pathway 164 // Conversion of Ribose to Deoxyribose 167 // Carbohydrate Constituents of // Proteins—Glycoproteins 167 // Transfer of Nucleotide Sugars Into the Golgi // Cisternae 172 // Sugars in Blood Group Proteins 172 // Enzymatic Conversion of A and B Blood // Types to Type O (Universal Donor) 173 // Lactose Intolerance 174 //

Glycobiology 174 // Summary 176 // Suggested Reading 180 // Multiple-Choice Questions 181 // 7 Glycogen and Glycogenolysis 183 // Glycogen Storage Disease Type I, von Gierke Disease (and Others: At Least 11 Types of Glycogen Storage Disease) 183 // Glycogen-The Storage Carbohydrate 184 // Glucose Metabolism in Muscle 184 // Glycogenin and Formation of Glycogen 184 // Glycogenolysis (Releasing Glucose from // Glycogen) 187 // Hormonal Control of Glycogen Metabolism // and Blood Glucose Level 192 // Glucagon 192 // Epinephrine 195 // Insulin 198 // Glycogen Phosphorylase 199 // Different Glucose Transporters in Different Tissues 200 // Summary 201 // Suggested Reading 204 // Multiple-Choice Questions 204 // 8. Glycolysis and Gluconeogenesis 207 // Hemolytic Anemia: Glyceraldehyde-3Phosphate Dehydrogenase Deficiency (A Rare Disease) 207 // Hemolytic Anemia 207 // Methemoglobin Reductase Pathway 207 // Rapoport-Luebering Shunt 207 // The Pentose Phosphate Pathway 208 // Glycolysis, the Emden-Meyerhof Pathway 209 // Phosphofructokinase Enzymes Involved in // the Conversion of Fructose-6-Phosphate to // Fructose-1,6-Bisphosphate 214 // Cell Proliferation and Tumor Growth—The // Warburg Effect 216 // Gluconeogenesis 216 // Alanine Cycle 217 // Glucose Can Be Formed From Glycerol 217 // Small-Molecule Regulation of // Gluconeogenesis 218 // Glucose Transporters 222 // Glucose Transporter Structure/Function 222 // Summary 222 // Suggested Reading 223 // Multiple-Choice Questions 224 // 9. Lipids 227 // Hypercholesterolemia 227 // Autosomal Recessive Hypercholesterolemia // Protein 230 // ApoB-100 Protein Mutations 230 // Normal LDL Function at Tissue Cells 231 // Biosynthesis of Cholesterol 231 // Inhibition of Liver HMG-CoA Reductase by Drugs (Statins) 233 // The ARH Protein 235 // Bile Acids 236 // Fatty Acids and Fat 236 //

Glycerol and Its Substituents; Triglycerides 240 // Fat (Triglyceride) Digestion and Uptake 242 // Chylomicrons 244 // P-Oxidation 245 // Activation and Transport of Fatty Acids Into Mitochondria 246 // Unsaturated Fatty Acids 252 // Ketone Bodies 252 // Lipid Metabolism, Lipid Droplets, and Hormonal Control 255 // Fatty Acid Synthesis 259 // Phospholipids and Membranes 265 // Lipins 266 // Synthesis and Degradation of Ceramide 268 // Glycosphingolipids 271 // Properties of Lipoproteins 273 // Lipid Anchoring of Proteins to Membranes 276 // Summary 276 // Suggested Reading 281 // Multiple-Choice Questions 283 // Case Study 285 // Familial Hypercholesterolemia 285 // Learning Questions 285 // Suggested Reading 285 // 10. Nucleic Acids and Molecular Genetics 287 // Huntington’s Disease, A Single-Gene Mutation 287 // Purines and Pyrimidines 289 // Base Pairing 292 // The Structure of DNA 295 // Biosynthesis of Purines and Pyrimidines 295 // Purine Interconversions 299 // Catabolism of Purine and Pyrimidine // Nucleotides 299 // Salvage Pathway 302 // Pyrimidine Catabolism 303 // Deoxyribose-Containing Nucleotides 304 // Formation of Deoxyribose From Ribose // Only in Its Nucleotide Form 304 // Disorders of Purine and Pyrimidine // Metabolism 305 // Biosynthesis of Deoxyribonucleic // Acid in the Nucleus 306 // Mitochondrial DNA Synthesis 311 // DNA Mutations and Damage 312 // Epigenetics 314 // Restriction Enzymes 317 // Probing Libraries for Specific Genes 320 // Hybridization Techniques 321 // Amplification of DNA Sequences: Polymerase Chain Reaction 322 // Identification of a Specific Gene on a // Chromosome 323 // Determining DNA Sequence 323 // Inhibitors of DNA Synthesis 326 // DNA Editing 328 // RNA Interference 332 // Coding DNA 333 // Noncoding DNA 333 // Introns 334 // Transposons 335 // Alu Elements 335 //

5‘-Capping of RNA Containing Exons and Introns 335 // Polyadenylation of Pre-mRNA 337 // Overall Transcription-Translation Process 337 // Intron Exclusion From Pre-mRNA 339 // Coding RNA 339 // Noncoding RNAs 340 // RNA Components of the Spliceosome 345 // RNA Secondary Structures 345 // Genomics 345 // Next-Generation Sequencing 348 // Proteomics 349 // Gene Therapy 350 // Summary 352 // Suggested Reading 354 // Multiple-Choice Questions 355 // 11. Protein Biosynthesis // Defects in Mitochondrial Oxidative // Phosphorylation and Disease: Deficiency in Mitochondrial Translation 357 // Protein Synthesis in the Mitochondrion 357 // Mitochondrial Encephalomyopathy With // Lactic Acidosis and Stroke-Like Episodes 357 // Protein Synthesis Directed by the Nucleus 359 // The Ribosome 360 // Structure of Transfer RNA 366 // Initiation: Amino Acid Transfer RNA Synthase 366 // Elongation and Peptidyltransferase Ribozyme 368 // Termination 371 // Inhibitors of Protein Synthesis 371 // Proteins Synthesized in the Cytoplasm but // Destined for the Mitochondria 371 // Proteins Destined for the Nucleus 372 // Proteins Destined for Other Sites, Including // the Plasma Membrane and Secretion // from the Cell 373 // Summary 373 // x Contents // Suggested Reading // Multiple-Choice Questions // 12. Transcription // Congenital Heart Disease: Mutations of // Transcription Factors // Normal Heart Development // Transcription Factors Control Heart // Development // GATA4 // Nkx2.5 // Tbx5 // Transcription Factors Involved in Cardiac // Hypertrophy // Transcription Factors and the Transcription // Complex // Enhancers // Coactivators and Corepressors // The Glucocorticoid Receptor as a Model // Transcription Factor // The Inactive Glucocorticoid Receptor in the Cytoplasm and Its Activation // Classes of Nuclear Receptors // Cell Membrane Receptors // Receptor Isoforms //

Chromatin // Summary , Suggested Reading // Multiple-Choice Questions // Case Study // Li—Fraumeni Syndrome // Learning Questions // Suggested Reading // 13. Metabolism of Amino Acids // Urea Cycle-Related Disease: // Hyperammonemia // The Urea Cycle // Amino Acid Metabolism: Amino and Amide Group Transfers // Transamination // Transamidation // Deamination // Oxidation of Amino Acids // Amino Acid Racemization // L-Amino Acid Decarboxylation // Metabolism of Amino Acids to Active // Substances // Methionine // Phenylalanine and Tyrosine // Formation of Catecholamines DOPA // (Dopamine, Norepinephrine, and Epinephrine) // Melanin // Blockages in the Metabolism of // Phenylalanine and Tyrosine and Disease // Tryptophan // Arginine // Histidine // Glutamate // Serine // Catabolism of Amino Acids // Summary // Suggested Reading // Multiple-Choice Questions // 14. Metabolism of Fat, Carbohydrate, and Nucleic Acids // Gaucher’s Disease: Most Common Lipid // Storage Disease // Lipid Metabolism , Fatty Acid Degradation // Fat as Storage Energy // Joint Regulation of Lipid and Carbohydrate // Metabolism // Glucagon and Glucagon-Like Peptides // Metabolism of Cholesterol // Sunlight and Vitamin D // Metabolism of Steroid Hormones Formed From Cholesterol // Bile Acid Metabolism // Carbohydrate Metabolism // Glycolysis // Gluconeogenesis // Vigorous Exercise and Gluconeogenesis // The Tricarboxylic Acid Cycle, Citric Acid // Cycle, or Kreb’s Cycle // The Electron Transport Chain // Nucleic Acid Metabolism // RNA Degradation // DNA Degradation // DNA Damage and Repair // Overview of Metabolism // Metabolism in Stem Cells // Summary // Suggested Reading // Multiple-Choice Questions 415 // 15. Polypeptide Hormones // Panhypopituitarism: Malfunction of the // Hypothalamus—Pituitary-End Organ Axis // Hormonal Signaling Pathways //

Signaling From Hypothalamus to Posterior Pituitary // Hormonal Signaling From the Hypothalamus to the Anterior Pituitary 475 // Models of Hormone Action of Anterior // Pituitary Hormones 484 // Adrenocorticotropic Hormone 484 // o-Melanocyte-Stimulating Hormone; // Melanotropin, Intermedin 484 // Growth Hormone 488 // Prolactin 488 // Thyroid-Stimulating Hormone, Thyrotropin 488 // The Gonadotropins: Luteinizing Hormone // and Follicle-Stimulating Hormone 490 // Overview of the Release and Functioning // of the Arginine Vasopressin and Oxytocin // Hormones From the Posterior Pituitary 493 // Orexins (Hypocretins): Hypothalamic // Hormones Controlling Sleep and Feeding 494 // Adiponectin From Adipose (Fat) Tissue 495 // Hormones of the Gastrointestinal Tract 497 // Gastrin 498 // Food Intake and Hormones 499 // Hormones Affecting Food Intake 509 // Summary 509 // Suggested Reading 514 // Multiple-Choice Questions 515 // 16. Steroid Hormones 517 // Stress 517 // Nociceptin 517 // Responses to Stress / 518 // Production of High Levels of Cortisol (Cushing’s Disease) and Subnormal Levels of Cortisol (Addison’s Disease) 522 // Adrenal Cortex 523 // Structures of Steroid Hormone Receptors 526 // Coactivators and Corepressors 534 // Physiological Functions of Steroid Hormones // From Specific Receptor Knockouts 535 // Steroid Transporting Proteins in Plasma 538 // Enzymatic Inactivation of Cortisol 538 // Cortisol and Aldosterone 538 // Dehydroepiandrosterone 541 // Structural Considerations of Steroid Hormones 544 // Receptor Activation 545 // Vitamin D Hormone 547 // Thyroid Hormone 548 // Environmental Xenobiotics That Agonize or // Antagonize the Estrogen Receptor 549 // Cross talk Between Steroid Receptors and Peptide Hormones 549 // Sex Hormones 550 // Peroxisome Proliferators and Their Receptors 551 // Glucocorticoid Induction of Programmed //

Cell Death (Apoptosis) 552 // Summary 554 // Suggested Reading 557 // Multiple-Choice Questions 558 // 17. Growth Factors and Cytokines 559 // Prospects for Cytokine Tumor Necrosis // Factor—Related Apoptosis-Inducing // Ligand and Ovarian Cancer 559 // Tumor Necrosis Factor-Related ApoptosisInducing Ligand and Its Mechanism 560 // The Tumor Necrosis Factor Superfamily 562 // Growth Factors 563 // Platelet-Derived Growth Factor 568 // Epidermal Growth Factor 572 // Transforming Growth Factor 574 // Fibroblast Growth Factor 577 // Neurotrophins and Nerve Growth Factor 579 // Colony-Stimulating Factor 583 // Erythropoietin 587 // Interferon 591 // Insulin-Like Growth Factors (IGF-I, IGF-II) 594 // Interleukins 596 // Overview 597 // Summary 597 // Suggested Reading 604 // Multiple-Choice Questions 605 // 18. Membrane Transport 607 // Cystic Fibrosis (Mucoviscidosis) and Aberrant Ion Transport 607 // Types of Membrane Transport 611 // Absorption of Large Molecules Binding to // Receptors on the Cell Surface 611 // Exocytosis 611 // Passive Diffusion (Osmosis) 613 // Facilitated Diffusion 614 // Active Transport Requiring Energy 616 // Simple and Coupled Transporters 617 // Ions and Gradients 619 // Entry of Magnesium and Divalent Ions Into // Cells 624 // Proton (H ’) Transport 625 // Monocarboxylate Transporter: // A Cotransporter (Symporter) 628 // Citrate Transporters in Mitochondria and Plasma Membrane 629 // Intestinal Transport of Di- and Tripeptides 629 // Amino Acid Transporters 630 // The Glutamate Synapse and Excitatory // Amino Acid Transporters 632 // Fatty Acid Transport Proteins 633 // Voltage-Gated Sodium Channels 635 // Epithelial Sodium Conductance Channel 636 // Multidrug Resistance Channel (MDR): A Member of the Adenosine Triphosphate-Binding Cassette Transporter Superfamily 638 // Blood-Brain Barrier 639 // Summary 639 //

Multiple-Choice Questions 642 // Case Study 643 // Cystic Fibrosis 643 // Learning Questions 644 // Suggested Reading 644 // Suggested Reading 644 // 19. Micronutrients (Metals and Iodine) 647 // Iron-deficiency Anemia 647 // Uptake of Iron During Digestion 650 // Hepcidin, A Peptide Hormone, is the Principal // Regulator of Iron Homeostasis 654 // Hemojuvelin, An Anchored Membrane // Protein Stimulates Hepcidin Transcription // Through Bone Morphogenic // (Morphogenetic) Proteins and Smad 655 // Heme Synthesis 658 // Hemoglobin Formation 659 // Trace Elements 667 // Trace Metals 667 // Copper 667 // Magnesium (Mg2+) 674 // Zinc (Zn2+) ’ 678 // Molybdenum (Mo2+) 680 // Selenium (Se2-) 682 // Selenodeiodinases 682 // Selenophosphate Synthase 683 // Calcium (Ca2*) 684 // Iodine (1) 694 // Summary 697 // Suggested Reading 698 // Multiple-Choice Questions 700 // 20. Vitamins and Nutrition 703 // Vitamin D Deficiency 703 // Vitamins 703 // Water-Soluble Vitamins 703 // Thiamine (Vitamin B1, Aneurine) 705 // Riboflavin (Vitamin B2) 707 // Niacin (Vitamin B3) 708 // Pantothenic Acid (Vitamin B5, Pantothenate) 709 // Pyridoxine, Pyridoxal, and Pyridoxamine // (Vitamin B6) 711 // Biotin (Vitamin H) 715 // Cobalamin (Vitamin B12) 716 // Folic Acid (Vitamin B9, Pteroylglutamic Acid) 720 // Ascorbic Acid (Vitamin C) 723 // Addiction 725 // Alcoholism 725 // Drugs 725 // Fat-Soluble Vitamins 726 // Vitamin A (3-Carotene) 726 // Vitamin D (1,25-Dihydroxyvitamin D3, Active Form) 729 // Vitamin E (a-Tocopherol) 732 // Vitamin K 733 // Balanced Nutrition 736 // Nutrient Intake 737 // Eye Health 737 // The Vegan Diet 737 // The Ketogenic (Keto) Diet and Weight Loss 738 // The Mediterranean Diet: Probably the // Healthiest Diet 739 // Dietary Considerations in Chronic Kidney // Disease 741 // Summary 744 // Suggested Reading 744 // Multiple-Choice Questions 745 //

Case Study 746 // Diet and Fatty Liver Disease 746 // Learning Questions 747 // Suggested Reading 747 // 21. Blood and Lymphatic System 749 // Deep Vein Thrombosis 749 // Factor V Leiden 749 // Blood-Clotting Mechanism 750 // Blood 752 // Transport of Oxygen 754 // Glycation of Proteins 761 // Carbon Dioxide 764 // Degradation of the Red Blood Cell 766 // Bilirubin 767 // Blood Cells 767 // Blood Proteins 768 // Blood Type and Rh Factor 768 // Origin of Nonself Blood Type Antibodies 771 // Rh Antigen 772 // Lymphatic System 772 // Thymosin 776 // Summary 777 // Suggested Reading 779 // Multiple-Choice Questions 780 // List of Abbreviations 783 // Appendix 1: Abbreviations of the Common // Amino Acids 793 // Appendix 2: The Genetic Code 795 // Appendix 3: Weights and Measures 797 // Appendix 4: Answer Key for Chapter Questions 799 // Index 831