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Bibliografická citace

0 (hodnocen0 x )
Fourth edition
Philadelphia : Elsevier, [2017]
xii, 617 stran : barevné ilustrace ;

ISBN 978-0-323-29616-8 (brožováno)
Terminologický slovník
Obsahuje bibliografie a rejstřík
CONTENTS // Part ONE // PRINCIPLES OF MOLECULAR STRUCTURE AND FUNCTION 1 // Chapter 1 // INTRODUCTION TO BIOMOLECULES 2 // Water Is the Solvent of Life 2 // Water Contains Hydronium Ions and Hydroxyl Ions 3 I  nizable Groups Are Characterized by Their pK Values 4 The Blood pH Is Tightly Regulated 4 Acidosis and Alkalosis Are Common in Clinical Practice 5 Bonds Are Formed by Reactions between Functional Groups 6 Isomeric Forms Are Common in Biomolecules 7 Properties of Biomolecules Are Determined by Their Noncovalent Interactions 8 // Triglycerides Consist of Fatty Acids and Glycerol 10 Monosaccharides Are Polyalcohols with a Keto Group or an Aldehyde Group 10 // Monosaccharides Form Ring Structures 11 // Complex Carbohydrates Are Formed by Glycosidic Bonds 11 // Polypeptides Are Formed from Amino Acids 14 // Nucleic Acids Are Formed from Nucleotides 14 // Most Biomolecules Are Polymers 15 // Summary 16 // Chapter 2 // INTRODUCTION TO PROTEIN STRUCTURE 18 // Amino Acids Are Zwitterions 18 // Amino Acid Side Chains Form Many Noncovalent Interactions 19 Peptide Bonds and Disulfide Bonds Form the Primary Structure of Proteins 20 // Proteins Can Fold Themselves into Many Shapes 22 a-Helix and ß-Pleated Sheet Are the Most Common Secondary Structures in Proteins 22 Globular Proteins Have a Hydrophobic Core 23 Proteins Lose Their Biological Activities When Their Higher-Order Structure Is Destroyed 24 The Solubility of Proteins Depends on pH and Salt Concentration 25 // Proteins Absorb
Ultraviolet Radiation 26 Proteins Can Be Separated by Their Charge or Their Molecular Weight 26 // Abnormal Protein Aggregates Can Cause Disease 27 Neurodegenerative Diseases Are Caused by Protein Aggregates 29 Protein Misfolding Can Be Contagious 30 Summary 31 // Chapter 3 // OXYGEN-BINDING PROTEINS: HEMOGLOBIN AND MYOGLOBIN 33 // The Heme Group Is the Oxygen-Binding Site of Hemoglobin and Myoglobin 33 // Myoglobin Is a Tightly Packed Globular Protein 34 Red Blood Cells Are Specialized for Oxygen Transport 34 The Hemoglobins Are Tetrameric Proteins 34 Oxygenated and Deoxygenated Hemoglobin Have Different Quaternary Structures 36 Oxygen Binding to Hemoglobin Is Cooperative 36 2,3-Bisphosphoglycerate Is a Negative Allosteric Effector of Oxygen Binding to Hemoglobin 37 Fetal Hemoglobin Has a Higher Oxygen-Binding Affinity Than Does Adult Hemoglobin 38 // The Bohr Effect Facilitates Oxygen Delivery 39 Most Carbon Dioxide Is Transported as Bicarbonate 39 Summary 40 // Chapter 4 // ENZYMATIC REACTIONS 41 // The Equilibrium Constant Describes the Equilibrium of the Reaction 41 // The Free Energy Change Is the Driving Force for Chemical Reactions 42 // The Standard Free Energy Change Determines the Equilibrium 43 Enzymes Are Both Powerful and Selective 43 The Substrate Must Bind to Its Enzyme before the Reaction Can Proceed 44 // Rate Constants Are Useful for Describing Reaction Rates 44 Enzymes Decrease the Free Energy of Activation 45 Many Enzymatic Reactions Can Be Described by Michaelis-Menten
Kinetics 46 ? and Vmax Can Be Determined Graphically 47 Substrate Half-Life Can Be Determined for First-Order but Not Zero-Order Reactions 48 // ? JKm Predicts the Enzyme Activity at Low Substrate Concentration 48 // Allosteric Enzymes Do Not Conform to Michaelis-Menten Kinetics 48 // Enzyme Activity Depends on Temperature and pH 49 Different Types of Reversible Enzyme Inhibition Can Be Distinguished Kinetically 49 // Covalent Modification Can Inhibit Enzymes Irreversibly 51 Enzymes Stabilize the Transition State 51 Chymotrypsin Forms a Transient Covalent Bond During Catalysis 52 Summary 53 // Chapter 5 COENZYMES 55 // Enzymes Are Classified According to Their Reaction Type 55 Adenosine Triphosphate Has Two Energy-Rich Bonds 56 ATP DONATES Phosphate in Phosphorylation Reactions 58 ATP Hydrolysis Drives Endergonic Reactions 59 Cells Always Try to Maintain a High Energy Charge 59 Dehydrogenase Reactions Require Specialized Coenzymes 59 Coenzyme A Activates Organic Acids 60 5-Adenosyl Methionine Donates Methyl Groups 62 Many Enzymes Require a Metal Ion 62 Summary 63 // Part TWO // GENETIC INFORMATION: DNA, RNA, AND PROTEIN SYNTHESIS 65 // Chapter 6 // DNA, RNA, AND PROTEIN SYNTHESIS 66 // All Living Organisms Use DNA as Their Genetic Databank 66 // DNA Contains Four Bases 68 // DNA Forms a Double Helix 68 // DNA Can Be Denatured 69 // DNA Is Supercoiled 69 // DNA Replication Is Semiconservative 70 // DNA Is Synthesized by DNA Polymerases 70 // DNA Polymerases Have Exonuclease Activities
71 // viii // Contents // Unwinding Proteins Present a Single-Stranded Template to the DNA Polymerases 72 // One of the New DNA Strands Is Synthesized Discontinuously 74 RNA Plays Key Roles in Gene Expression 76 The a Subunit Recognizes Promoters 76 DNA Is Faithfully Copied into RNA 77 Some RNAs Are Chemically Modified After Transcription 79 The Genetic Code Defines the Structural Relationship between mRNA and Polypeptide 80 // Transfer RNA Is the Adapter Molecule in Protein Synthesis 81 Amino Acids Are Activated by an Ester Bond with the 3’ Terminus of the tRNA 82 // Many Transfer RNAs Recognize More Than One Codon 83 Ribosomes Are the Workbenches for Protein Synthesis 83 The Initiation Complex Brings Together Ribosome, Messenger RNA, and Initiator tRNA 85 // Polypeptides Grow Stepwise from the Amino Terminus to the Carboxyl Terminus 85 // Protein Synthesis Is Energetically Expensive 88 Gene Expression Is Tightly Regulated 88 // A Repressor Protein Regulates Transcription of the lac Operon in E. coli 88 // Anabolic Operons Are Repressed by the End Product of the Pathway 89 // Glucose Regulates the Transcription of Many Catabolic Operons 90 Transcriptional Regulation Depends on DNA-Binding Proteins 91 Summary 92 // Chapter 7 // THE HUMAN GENOME 94 // Chromatin Consists of DNA and Histones 94 The Nucleosome Is the Structural Unit of Chromatin 95 Covalent Histone Modifications Regulate DNA Replication and Transcription 95 // DNA Methylation Silences Genes 95 // All Eukaryotic Chromosomes
Have a Centromere, Telomeres, and Replication Origins 97 // Telomerase Is Required (but Not Sufficient) for Immortality 97 Eukaryotic DNA Replication Requires Three DNA Polymerases 99 Most Human DNA Does Not Code for Proteins 100 Gene Families Originate by Gene Duplication 100 The Genome Contains Many Tandem Repeats 101 Some DNA Sequences Are Copies of Functional RNAs 101 Many Repetitive DNA Sequences Are (or Were) Mobile 102 LI Elements Encode a Reverse Transcriptase 103 ALU Sequences Spread with the Help of LI Reverse Transcriptase 105 Mobile Elements Are Dangerous 105 Humans Have Approximately 20,000 Genes 105 Transcriptional Initiation Requires General Transcription Factors 106 Genes Are Surrounded by Regulatory Sites 107 Gene Expression Is Regulated by DNA-Binding Proteins 107 Long Noncoding RNAs Play Roles in Gene Expression 108 mRNA Processing Starts During Transcription 109 Translational Initiation Requires Many Initiation Factors 111 mRNA Processing and Translation Are Often Regulated 113 Small RNA Molecules Inhibit Gene Expression 115 Mitochondria Have Their Own DNA 116 Human Genomes Are Very Diverse 117 Human Genomes Have Many Low-Frequency Copy Number Variations 117 Summary 118 // Chapter 8 // PROTEIN TARGETING AND PROTEOSTASIS 120 // A Signal Sequence Directs Polypeptides to the Endoplasmic Reticulum 120 // Glycoproteins Are Processed in the Secretory Pathway 121 The Endocytic Pathway Brings Proteins into the Cell 124 Lysosomes Are Organelles of Intracellular Digestion
126 Autophagy Recycles Cellular Proteins and Organelles 127 Poorly Folded Proteins Are Either Repaired or Destroyed 127 Ubiquitin Marks Proteins for Destruction 127 // The Proteostatic System Protects Cells from Abnormal Proteins 129 Summary 131 // Chapter 9 // INTRODUCTION TO GENETIC DISEASES 132 // Four Types of Genetic Disease 132 // Mutations Occur in the Germline and in Somatic Cells 133 Mutations Are an Important Cause of Poor Health 134 Small Mutations Lead to Abnormal Proteins 134 Most Mutations Are Caused by Replication Errors 135 Mutations Can Be Induced by Radiation and Chemicals 135 Mismatch Repair Corrects Replication Errors 136 Missing Bases and Abnormal Bases Need to Be Replaced 138 Nucleotide Excision Repair Removes Bulky Lesions 139 Repair of DNA Double-Strand Breaks Is Difficult 139 Hemoglobin Genes Form Two Gene Clusters 141 Many Point Mutations in Hemoglobin Genes Are Known 142 Sickle Cell Disease Is Caused by a Point Mutation in the ß-Chain Gene 143 // SA Heterozygotes Are Protected from Tropical Malaria 144 «-Thalassemia Is Most Often Caused by Large Deletions 145 Many Different Mutations Can Cause ß-Thalassemia 146 Fetal Hemoglobin Protects from the Effects of ß-Thalassemia and Sickle Cell Disease 147 // Polygenic Diseases Have Multiple Genetic Risk Factors 147 Genetic Risk Factors Are Discovered in Genome-Wide Association Studies 148 Summary 149 // Chapter 10 // VIRUSES 152 // Viruses Can Replicate Only in a Host Cell 152 Bacteriophage T4 Destroys Its
Host Cell 153 DNA Viruses Substitute Their Own DNA for the Host Cell DNA 153 A, Phage Can Integrate Its DNA into the Host Cell Chromosome 154 // RNA Viruses Require an RNA-Dependent RNA Polymerase 157 Retroviruses Replicate through a DNA Intermediate 157 Plasmids Are Small “Accessory Chromosomes” or “Symbiotic Viruses” of Bacteria 160 // Bacteria Can Exchange Genes by Transformation and Transduction 160 // Jumping Genes Can Change Their Position in the Genome 162 Summary 164 // Chapter 11 // DNA TECHNOLOGY 165 // Restriction Endonucleases Cut Large DNA Molecules into Smaller Fragments 165 // Large Probes Are Used to Detect Copy Number Variations 165 Small Probes Are Used to Detect Point Mutations 166 Southern Blotting Determines the Size of Restriction Fragments 167 DNA Can Be Amplified with the Polymerase Chain Reaction 168 PCR Is Used for Preimplantation Genetic Diagnosis 169 Allelic Heterogeneity Is the Greatest Challenge for Molecular Genetic Diagnosis 170 // Normal Polymorphisms Are Used as Genetic Markers 170 Tandem Repeats Are Used for DNA Fingerprinting 171 DNA Microarrays Can Be Used for Genetic Screening 172 DNA Microarrays Are Used for the Study of Gene Expression 174 DNA Is Sequenced by Controlled Chain Termination 174 Massively Parallel Sequencing Permits Cost-Efficient Whole-Genome Genetic Diagnosis 175 Gene Therapy Targets Somatic Cells 177 Viruses Are Used as Vectors for Gene Therapy 177 Retroviruses Can Splice a Transgene into the Cell’s Genome 178 Genome
Editing Is Based on the Making and Healing of DNA Double Strand Breaks 179 // Designer Nucleases Are Used for Genome Editing 180 Antisense Oligonucleotides Can Block the Expression of Rogue Genes 181 // Contents // On Be Altered in Animals 181 // ~ s - _r-4recific Gene Expression Can Be Engineered into Animals 183 Hsman Germline Genome Editing Is Technically Possible 184 // Summary 184 // Rart THREE // CELL AND TISSUE STRUCTURE 187 // Chapter 12 // BIOLOGICAL MEMBRANES 188 // Membranes Consist of Lipid and Protein 188 7 • ’rhoglycerides Are the Most Abundant Membrane Lipids 188 M Sphingolipids Are Glycolipids 190 - ’esterol Is the Most Hydrophobic Membrane Lipid 191 Membrane Lipids Form a Bilayer 192 ??? Lipid Bilayer Is a Two-Dimensional Fluid 192 The Lipid Bilayer Is a Diffusion Barrier 193 Membranes Contain Integral and Peripheral Membrane Proteins 194 // \Irmbranes Are Asymmetrical 194 Membranes Are Fragile 196 // Membrane Proteins Carry Solutes Across the Lipid Bilayer 196 ~’insport against an Electrochemical Gradient Requires Metabolic Energy 198 // Active Transport Consumes ATP 199 > cium Cotransport Brings Molecules into the Cell 199 Summary 201 // Chapter 13 // THE CYTOSKELETON 203 // The Erythrocyte Membrane Is Reinforced by a Spectrin Network 203 // Keratins Give Strength to Epithelia 204 Actin Filaments Are Formed from Globular Subunits 206 Striated Muscle Contains Thick and Thin Filaments 207 Myosin Is a Two-Headed Molecule with ATPase Activity 207 Muscle Contraction
Requires Calcium and ATP 210 The Cytoskeleton of Skeletal Muscle Is Linked to the Extracellular Matrix 211 // Microtubules Consist of Tubulin 213 Eukaryotic Cilia and Flagella Contain a 9 + 2 Array of Microtubules 214 // Cells Form Specialized Junctions with Other Cells and with the Extracellular Matrix 214 Summary 216 // Chapter 14 // THE EXTRACELLULAR MATRIX 218 // Collagen Is the Most Abundant Protein in the Human Body 218 The Tropocollagen Molecule Forms a Long Triple Helix 220 Collagen Fibrils Are Staggered Arrays of Tropocollagen Molecules 220 // Collagen Is Subject to Extensive Posttranslational Processing 220 Collagen Metabolism Is Altered in Aging and Disease 222 Many Genetic Defects of Collagen Structure and Biosynthesis Are Known 223 // Elastic Fibers Contain Elastin and Fibrillin 224 The Amorphous Ground Substance Contains Hyaluronic Acid 225 Sulfated Glycosaminoglycans Are Covalently Bound to Core Proteins 226 // Cartilage Contains Large Proteoglycan Aggregates 227 Proteoglycans Are Synthesized in the ER and Degraded in Lysosomes 228 // Mucopolysaccharidoses Are Caused by Deficiency of Glycosaminoglycan-Degrading Enzymes 229 Bone Consists of Calcium Phosphates in a Collagenous Matrix 230 Basement Membranes Contain Type IV Collagen, Laminin, and Heparan Sulfate Proteoglycans 230 Fibronectin Glues Cells and Collagen Fibers Together 231 Summary 232 // Part FOUR // MOLECULAR PHYSIOLOGY 235 // Chapter 15 // EXTRACELLULAR MESSENGERS 236 // Steroid Hormones Are Made from
Cholesterol 236 Progestins Are the Biosynthetic Precursors of All Other Steroid Hormones 238 // Thyroid Hormones Are Synthesized from Protein-Bound Tyrosine 242 // T4 Becomes Activated to T3 in the Target Tissues 243 Both Hypothyroidism and Hyperthyroidism Are Common Disorders 244 // Insulin Is Released Together with the C-Peptide 245 Proopiomelanocortin Forms Several Active Products 245 Angiotensin Is Formed from Circulating Angiotensinogen 246 Immunoassays Are Used for Determination of Hormone Levels 247 // Catecholamines Are Synthesized from Tyrosine 249 Indoleamines Are Synthesized from Tryptophan 249 Histamine Is Produced by Mast Cells and Basophils 251 Neurotransmitters Are Released at Synapses 251 Acetylcholine Is the Neurotransmitter of the Neuromuscular Junction 252 // There Are Many Neurotransmitters 252 Summary 254 // Chapter 16 // INTRACELLULAR MESSENGERS 256 // Receptor-Hormone Interactions Are Noncovalent, Reversible, and Saturable 256 // Many Neurotransmitter Receptors Are Ion Channels 257 Steroid and Thyroid Hormones Bind to Transcription Factors 258 Seven-Transmembrane Receptors Are Coupled to G Proteins 258 Adenylate Cyclase Is Regulated by G Proteins 260 Hormones Can Both Activate and Inhibit the cAMP Cascade 261 Cytoplasmic Calcium Is an Important Intracellular Signal 263 Phospholipase C Generates Two Second Messengers 263 Both cAMP and Calcium Regulate Gene Transcription 264 Muscle Contraction and Exocytosis Are Triggered by Calcium 265 Atrial Natriuretic
Factor Acts Through a Membrane-Bound Guanylate Cyclase 265 // Nitric Oxide Stimulates a Soluble Guanylate Cyclase 267 cGMP Is a Second Messenger in Retinal Rod Cells 268 Receptors for Insulin and Growth Factors Are Tyrosine-Specific Protein Kinases 269 // Growth Factors and Insulin Trigger Multiple Signaling Cascades 271 // Cytokine Receptors Use the JAK-STAT Pathway 271 // Many Receptors Become Desensitized After Overstimulation 273 // Summary 273 // Chapter 17 // PLASMA PROTEINS 275 // Plasma Proteins Are Both Synthesized and Destroyed in the ’ // Liver 275 // Albumin Prevents Edema 275 Albumin Binds Many Small Molecules 277 Some Plasma Proteins Are Specialized Carriers of Small Molecules 277 // Deficiency of oq-Anti trypsin Causes Lung Emphysema 278 Levels of Plasma Proteins Are Affected by Many Diseases 279 Blood Components Are Used for Transfusions 280 Blood Clotting Must Be Tightly Controlled 281 Platelets Adhere to Exposed Subendothelial Tissue 281 Insoluble Fibrin Is Formed from Soluble Fibrinogen 283 Thrombin Is Derived from Prothrombin 284 Factor X Can Be Activated by the Extrinsic and Intrinsic Pathways 284 // Negative Controls Are Necessary to Prevent Thrombosis 286 Plasmin Degrades the Fibrin Clot 287 // Contents // Heparin and Vitamin ? Antagonists Are Used as Anticoagulants 288 Clotting Factor Deficiencies Cause Abnormal Bleeding 289 Tissue Damage Causes Release of Cellular Enzymes into Blood 289 Summary 292 // Chapter 18 // DEFENSE MECHANISMS 294 // Lipophilic
Xenobiotics Are Metabolized to Water-Soluble Products 294 // Cytochrome P-450 Is Involved in Phase I Metabolism 294 Phase II Metabolism Makes Xenobiotics Water-Soluble for Excretion 296 // Phase HI Metabolism Excretes Xenobiotic Metabolites 297 Drug-Metabolizing Enzymes Are Inducible 298 The Innate Immune System Uses Pattern Recognition Receptors 298 Infection Triggers Inflammation 299 Lymphocytes Possess Antigen Receptors 300 ? Lymphocytes Produce Immunoglobulins 301 Antibodies Consist of Two Light Chains and Two Heavy Chains 301 Different Immunoglobulin Classes Have Different Properties 303 Adaptive Immune Responses Are Based on Clonal Selection 305 Immunoglobulin Genes Are Rearranged during B-Cell Development 306 // The ?-Cell Receptor Recruits Cytosolic Tyrosine Protein Kinases 309 Mediators of Inflammation Are Produced from Arachidonic Acid 310 Prostaglandins Are Synthesized in All Tissues 311 Prostanoids Participate in Many Physiological Processes 312 Leukotrienes Are Produced by the Lipoxygenase Pathway 312 Antiinflammatory Drugs Inhibit the Synthesis of Eicosanoids 312 Summary 314 // Chapter 19 // CELLULAR GROWTH CONTROL AND CANCER 316 // The Cell Cycle Is Controlled at Checkpoints 316 Cells Can Be Grown in Culture 317 Cyclins Play Key Roles in Cell Cycle Control 317 Retinoblastoma Protein Guards the Gj Checkpoint 317 Cell Proliferation Is Triggered by Mitogens 318 Mitogens Regulate Gene Expression 319 Cells Can Commit Suicide 320 Cancers Are Monoclonal in Origin 322
Cancer Is Caused by Activation of Growth-Promoting Genes and Inactivation of Growth-Inhibiting Genes 323 Some Retroviruses Contain an Oncogene 324 Retroviruses Can Cause Cancer by Inserting Themselves Next to a Cellular Proto-Oncogene 325 // Many Oncogenes Code for Components of Mitogenic Signaling Cascades 326 // Cancer Susceptibility Syndromes Are Caused by Inherited Mutations in Tumor Suppressor Genes 329 Many Tumor Suppressor Genes Are Known 330 Components of the Cell Cycle Machinery Are Abnormal in Most Cancers 331 // DNA Damage Causes Either Growth Arrest or Apoptosis 332 Most Spontaneous Cancers Are Defective in p53 Action 333 The PI3K/protein Kinase ? Pathway Is Activated in Many Cancers 334 The Products of Some Viral Oncogenes Neutralize the Products of Cellular Tumor Suppressor Genes 334 Tumors Become More Malignant through Darwinian Selection 336 Intestinal Polyps Are Benign Lesions 336 Intestinal Polyps Can Evolve into Colon Cancer 337 Summary 338 // Part FIVE // METABOLISM 341 // Chapter 20 // DIGESTIVE ENZYMES 342 // Saliva Contains a-Amylase and Lysozyme 342 Protein and Fat Digestion Start in the Stomach 343 The Pancreas Is a Factory for Digestive Enzymes 344 Fat Digestion Requires Bile Salts 344 // Some Digestive Enzymes Are Anchored to the Surface of the Microvilli 346 // Poorly Digestible Nutrients Cause Flatulence 347 // Many Digestive Enzymes Are Released as Inactive Precursors 348 // Summary 349 // Chapter 21 // INTRODUCTION TO METABOLIC PATHWAYS 351 // Alternative
Substrates Can Be Oxidized in the Body 351 Metabolic Processes Are Compartmentalized 352 Free Energy Changes in Metabolic Pathways Are Additive 352 Most Metabolic Pathways Are Regulated 353 Feedback Inhibition and Feedforward Stimulation Are the Most Important Regulatory Principles 353 Metabolism Is Regulated to Ensure Homeostasis 354 Inherited Enzyme Deficiencies Cause Metabolic Diseases 354 Vitamin Deficiencies, Toxins, and Endocrine Disorders Can Disrupt Metabolic Pathways 355 Summary 356 // Chapter 22 // GLYCOLYSIS, TRICARBOXYLIC ACID CYCLE, AND OXIDATIVE PHOSPHORYLATION 357 // Glucose Uptake into the Cells Is Regulated 357 Glucose Degradation Begins in the Cytoplasm and Ends in the Mitochondria 358 // Glycolysis Begins with ATP-Dependent Phosphorylations 359 Most Glycolytic Intermediates Have Three Carbons 360 Phosphofructokinase Is the Most Important Regulated Enzyme of Glycolysis 361 // Lactate Is Produced under Anaerobic Conditions 362 Pyruvate Is Decarboxylated to Acetyl-CoA in the Mitochondria 363 The TCA Cycle Produces Two Molecules of Carbon Dioxide for Each Acetyl Residue 363 // Reduced Coenzymes Are the Most Important Products of the TCA Cycle 366 // Oxidative Pathways Are Regulated by Energy Charge and [NADH]/[NAD+] Ratio 366 // The TCA Cycle Provides a Pool of Metabolic Intermediates 367 Antiporters Transport Metabolites across the Inner Mitochondrial Membrane 369 // The Respiratory Chain Channels Electrons from NADH and FADH2 to Molecular Oxygen 370 The Standard
Reduction Potential Is the Tendency to Donate Electrons 371 // The Respiratory Chain Contains Flavoproteins, Iron-Sulfur Proteins, Cytochromes, Ubiquinone, and Protein-Bound Copper 372 The Respiratory Chain Contains Large Multiprotein Complexes 372 The Respiratory Chain Creates a Proton Gradient 373 The Proton Gradient Drives ATP Synthesis 374 The Efficiency of Glucose Oxidation Is Close to 40% 375 Oxidative Phosphorylation Is Limited by the Supply of ADP 376 Brown Adipose Tissue Contains an Uncoupling Protein 376 Mutations in Mitochondrial DNA Can Cause Disease 377 Summary 378 // Chapter 23 // OXYGEN DEFICIENCY AND OXYGEN TOXICITY 380 // Ischemia Leads to Infarction 380 // Oxidative Phosphorylation Is Inhibited by Many Poisons 381 Hypoxia Inducible Factor Adjusts Cell Metabolism to Hypoxia 383 Reactive Oxygen Derivatives Are Formed During Oxidative Metabolism 384 // The Respiratory Chain Is a Major Source of Superoxide 384 Cells Have Specialized Enzymes to Destroy Reactive Oxygen Species 385 // Free Radical Formation Is Affected by Energy Supply and Energy Consumption 386 // Some Vitamins and Phytochemicals Can Scavenge Free Radicals 387 The NRF2 Transcription Factor Coordinates Defenses Against Reactive Oxygen Species 388 // Phagocytic Cells Use Reactive Oxygen Species for Intracellular Killing 389 Summary 390 // Contents // Chapter 24 // CARBOHYDRATE METABOLISM 392 // - - equate Blood Glucose Level Must Be Maintained at All // Tiroes 392 // C .. neogenesis Bypasses the Three
Irreversible Reactions of Glycolysis 392 // Fz~ Ae:ds Cannot Be Converted into Glucose 393 C . iysis and Gluconeogenesis Are Regulated by Honnones 394 // L . • sis and Gluconeogenesis Are Fine Tuned by Allosteric // -"ectors and Hormone-Induced Enzyme Phosphorylations 394 f >e-2,6-Bisphosphate Switches the Liver from Z -coneogenesis to Glycolysis 396 < cic vmase Is Regulated by Two Regulatory Proteins 396 i hydrate Is Stored as Glycogen 398 . :qen Is Synthesized from Glucose 398 €5y : qen Is Degraded by Phosphorolytic Cleavage 399 t- - Dgcn Metabolissm Is Regulated by Hormones and Metabolites 400 // . cen Accumulates in Several Enzyme Deficiencies 403 "-er Is Channeled into Glycolysis/Gluconeogenesis 404 Excess Fructose Is Problematic 404 // c cess Galactose Is Channeled into the Pathways of Glucose Metabolism 406 // —: Pentose Phosphate Pathway Supplies NADPH and Ribose-5-Phosphate 407 // h-ucr >e Is the Principal Sugar in Seminal Fluid 409 // " Sugars and Sugar Acids Are Made from Glucose 409 // Sumary 410 // Chapter 25 // THE METABOLISM OF FATTY ACIDS AND TRIGLYCERIDES 412 // • z~ Acids Differ in Chain Length and Number of Double // Bonds 412 // * microns Transport Triglycerides from the Intestine to Other Tissues 414 // Vi rose Tissue Is Specialized for the Storage of Triglycerides 415 // * :* Metabolism in Adipose Tissue Is Under Hormonal // Control 416 // - Acids Are Transported into the Mitochondrion 417 Pxidation Produces Acetyl-CoA, NADH, and FADH2 418 // special
Fatty Acids Require Special Reactions 419 // Tr ? Liver Converts Excess Fatty Acids to Ketone Bodies 420 // - Acids Are Synthesized from Acetyl-CoA 423 // - cctyl-CoA Is Shuttled into the Cytoplasm as Citrate 424 // - iny Acid Synthesis Is Regulated by Hormones and // Metabolites 424 // - MP-Activated Protein Kinase Adapts Metabolic Pathways to // Cellular Energy Status 426 // M >t Fatty Acids Can Be Synthesized from Palmitate 427 // - • Acids Regulate Gene Expression 428 // F • unsaturated Fatty Acids Can Be Oxidized Nonenzymatically 429 nummary 429 // Chapter 26 // THE METABOLISM OF MEMBRANE LIPIDS 432 // : ¦ sphatidic Acid Is an Intermediate in Phosphoglyceride Synthesis 432 // PL sphoglycerides Are Remodeled Continuously 432 ’"ingolipids Are Synthesized from Ceramide 433 l rnciencies of Sphingolipid-Degrading Enzymes Cause Lipid Storage Diseases 434 // Cholesterol Is the Least Soluble Membrane Lipid 438 Cholesterol Is Derived from Both Endogenous Synthesis and the Diet 438 // Cholesterol Biosynthesis Is Regulated at the Level of HMG-CoA Reductase 439 // 5 le Acids Are Synthesized from Cholesterol 440 : le Acids Are Subject to Extensive Enterohepatic Circulation 441 Most Gallstones Consist of Cholesterol 443 // Mimmary 443 // Chapter 27 // LIPID TRANSPORT 445 // Most Plasma Lipids Are Components of Lipoproteins 445 Lipoproteins Have Characteristic Lipid and Protein Compositions 446 // Dietary Lipids Are Transported by Chylomicrons 447 VLDL Is a Precursor of LDL 447 LDL
Is Removed by Receptor-Mediated Endocytosis 449 Cholesterol Regulates Its Own Metabolism 450 HDL Is Needed for Reverse Cholesterol Transport 451 Lipoproteins Can Initiate Atherosclerosis 452 Lipoproteins Respond to Diet and Lifestyle 454 Hyperlipoproteinemias Are Grouped into Five Phenotypes 456 Hyperlipidemias Are Treated with Diet and Drugs 459 Summary 461 // Chapter 28 // AMINO ACID METABOLISM 463 // Amino Acids Can Be Used for Gluconeogenesis and Ketogenesis 463 // The Nitrogen Balance Indicates the Net Rate of Protein Synthesis 463 // The Amino Group of Amino Acids Is Released as Ammonia 464 Ammonia Is Detoxified to Urea 465 Urea Is Synthesized in the Urea Cycle 465 Hyperammonemia Can Be Treated with Diet and Drugs 467 Some Amino Acids Are Closely Related to Common Metabolic Intermediates 470 // Glycine, Serine, and Threonine Are Glucogenic 470 Proline, Arginine, Ornithine, and Histidine Are Degraded to Glutamate 472 // Methionine and Cysteine Are Metabolically Related 473 Valine, Leucine, and Isoleucine Are Degraded by Transamination and Oxidative Decarboxylation 475 Phenylalanine and Tyrosine Are Both Glucogenic and Ketogenic 477 // Melanin Is Synthesized from Tyrosine 477 Lysine and Tryptophan Have Lengthy Catabolic Pathways 480 The Liver Is the Most Important Organ of Amino Acid Metabolism 481 // Glutamine Participates in Renal Acid-Base Regulation 483 Summary 484 // Chapter 29 // METABOLISM OF IRON AND HEME 486 // Iron Is Conserved Very Efficiently in the Body 486 Iron
Uptake by Cells Is Regulated 487 Dietary Iron Is Absorbed in the Duodenum 487 Iron Deficiency Is the Most Common Micronutrient Deficiency Worldwide 490 // Bone Marrow and Liver Are the Most Important Sites of Heme Synthesis 491 // Heme Is Synthesized from Succinyl-CoA and Glycine 492 Porphyrias Are Caused by Deficiencies of Heme-Synthesizing Enzymes 493 // Heme Is Degraded to Bilirubin 494 Bilirubin Is Conjugated and Excreted by the Liver 495 Elevations of Serum Bilirubin Cause Jaundice 496 Many Diseases Can Cause Jaundice 497 Summary 499 // Chapter 30 // THE METABOLISM OF PURINES AND PYRIMIDINES 501 // Purine Synthesis Starts with Ribose-5-Phosphate 501 Purines Are Degraded to Uric Acid 502 Free Purine Bases Can Be Salvaged 503 Pyrimidines Are Synthesized from Carbamoyl Phosphate and Aspartate 503 // DNA Synthesis Requires Deoxyribonucleotides 504 Many Antineoplastic Drugs Inhibit Nucleotide Metabolism 504 Uric Acid Has Limited Water Solubility 506 Hyperuricemia Causes Gout 508 // xii // Contents // Abnormalities of Purine-Metabolizing Enzymes Can Cause Gout 509 Gout Can Be Treated with Drugs 509 Summary 510 // Chapter 31 // MICRONUTRIENTS 511 // Riboflavin Is a Precursor of Flavin Mononucleotide and Flavin Adenine Dinucleotide 511 Niacin Is a Precursor of NAD and NADP 512 Thiamine Deficiency Causes Weakness and Amnesia 514 Vitamin Plays a Key Role in Amino Acid Metabolism 515 Pantothenic Acid Is a Building Block of Coenzyme A 516 Biotin Is a Coenzyme in Carboxylation Reactions
516 Folic Acid Deficiency Causes Megaloblastic Anemia 517 Vitamin B12 Requires Intrinsic Factor for Its Absorption 519 Vitamin C Is a Water-Soluble Antioxidant 521 Retinol, Retinal, and Retinoic Acid Are the Active Forms of Vitamin A 523 // Vitamin D Is a Prohormone 525 // Vitamin E Prevents Lipid Oxidation 526 // Many Vitamins and Phytochemicals Are Antioxidants 527 // Vitamin ? Is Required for Blood Clotting 528 // Zinc Is a Constituent of Many Enzymes 528 // Copper Participates in Reactions of Molecular Oxygen 529 // Some Trace Elements Serve Very Specific Functions 530 // Summary 531 // Chapter 32 // INTEGRATION OF METABOLISM 533 // Insulin Is Released in Response to Elevated Glucose 533 Insulin Stimulates the Utilization of Nutrients 534 Protein Synthesis Is Coordinated by the mTOR Complex 535 Glucagon Maintains the Blood Glucose Level 536 Catecholamines Mediate the Flight-or-Fight Response 536 Glucocorticoids Are Released in Chronic Stress 537 Energy Is Expended Continuously 538 Stored Fat and Glycogen Are Degraded between Meals 539 Adipose Tissue Is the Most Important Energy Depot 540 The Liver Converts Dietary Carbohydrates to Glycogen and Fat after a Meal 541 // The Liver Maintains the Blood Glucose Level During Fasting 541 Ketone Bodies Provide Lipid-Based Energy During Fasting 544 Obesity Is Common in All Affluent Countries 544 Appetite Control Is the Most Important Determinant of Obesity 546 // Obesity Is Related to Insulin Resistance 547 // Diabetes Is Caused by Insulin
Deficiency or Insulin Resistance 549 // In Diabetes, Metabolism Is Regulated as in Starvation 550 Diabetes Is Diagnosed with Laboratory Tests 551 Diabetes Leads to Late Complications 552 Many Drugs Are Available for Diabetes Treatment 553 Contracting Muscle Has Three Energy Sources 553 Catecholamines Coordinate Metabolism during Exercise 555 Physical Exercise Leads to Adaptive Changes 557 Ethanol Is Metabolized to Acetyl-CoA in the Liver 558 Liver Metabolism Is Deranged by Alcohol 560 Alcohol Abuse Leads to Fatty Liver and Liver Cirrhosis 561 Most “Diseases of Civilization” Are Caused by Aberrant Lifestyles 561 // Aging Is the Greatest Challenge for Medical Research 564 Antiaging Treatments Are Being Investigated 565 Summary 566 // ANSWERS TO QUESTIONS 569 GLOSSARY 571 CREDITS 590 INDEX 591 // EXTRA ONLINE-ONLY CASE STUDIES // The Mafia Boss Viral Gastroenteritis Death in Installments A Mysterious Death To Treat or Not to Treat? // Yellow Eyes // An Abdominal Emergency Shortness of Breath Itching // Abdominal Pain Rheumatism // A Bank Manager in Trouble Kidney Problems Gender Blender Man Overboard! // Spongy Bones Blisters // The Sunburned Child Too Much Ammonia // ANSWERS TO CASE STUDIES

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