Integrative Human Biochemistry. A Textbook for Medical Biochemistry

Description

Foreword to the First Edition Leopoldo De Meis’ Legacy: A Biochemistry Textbook with a Difference Foreword to the Second Edition Preface to the First Edition Presentation of Book Structure Preface to the Second Edition References Acknowledgments Contents Part I: The Molecules of Life Chapter 1: Introduction: Life Is Made of Molecules! 1.1 Selected Illustrative Example #1: The Molecular Origin of Life 1.1.1 The Replicator Hypothesis 1.1.2 The Metabolism Hypothesis 1.2 Selected Illustrative Example #2: Viruses—Molecular Machines Interfering with Life 1.3 Selected Illustrative Example #3: Molecules as Tools—Drug Discovery and Development Challenging Case 1.1: The Origin of Life and Panspermia Source Case Description Questions Biochemical Insights Final Discussion Challenging Case 1.2: Science in Fiction—Mighty Weakness vs. Micropower Source Case Description Questions Biochemical Insights Final Discussion Challenging Case 1.3: Mars—NASA’s Laboratory for the Origin of Life … On Earth! Source Case Description Questions Biochemical Insight Final Discussion Astrobiology Extraterrestrial Exporting of Life Selected Bibliography Chapter 2: The Chemistry and Physics of Life 2.1 The Basics of Chemistry in Cells and Tissues 2.1.1 Principal Biological Buffers 2.2 More than Only Chemistry: There Is Physics Too Challenging Case 2.1: Going Deep into Acidosis Source Case Description Questions Biochemical Insights Final Discussion Challenging Case 2.2: Reindeer Know the Color of UV Light Source Case Description Questions Biochemical Insight Final Discussion: Examples of Missing and Misplaced Colors in Literature and Music Challenging Case 2.3: Malacocephalus—The Strange Case of the Radioactive Fish from the Deep Sea Source Case Description A Modern Interpretation Questions Biochemical Insight Final Discussion Scientific Knowledge Through Time Luminescent Art Bioluminescent Bays Alternative Case Study: Marie Curie and the Radium Girls Selected Bibliography Chapter 3: The Families of Biological Molecules 3.1 Lipids and the Organization of Their Supramolecular Assemblies 3.1.1 The Structure of Biological Membranes 3.1.2 The Structure of Lipoproteins 3.2 Saccharides and Their Polymers and Derivatives 3.2.1 From Monomers to Polymers: Polysaccharides 3.2.2 Molecular Conjugates of Mono- and Oligosaccharides 3.2.3 Molecular Conjugates of Oligosaccharides 3.2.4 Polymers of Saccharide Conjugates: Nucleic Acids 3.3 Amino Acids and Their Polymers: Peptides and Proteins 3.3.1 From Monomers to Polymers: Peptides and Proteins 3.3.2 Structure and Function in Proteins 3.3.3 Cooperative Interplay Between Tertiary-Level and Quaternary-Level Structure 3.3.4 Enzymes 3.3.4.1 The Importance of Studying Enzymes 3.3.4.2 The Nomenclature of Enzymes Challenging Case 3.1: Biochemistry in Dali’s (he)art Source Case Description Questions Biochemical Insights Final Discussion Further Reading Challenging Case 3.2: From Best with Proteins to Worst with DNA Source Case Description 3.5.2.1 The Protein Vision The DNA Vertigo Questions Biochemical Insights Final Discussion Challenging Case 3.3: London Fatberg Analysis—Impact of Urban Obesity on the Metropolitan Vasculature Source Case Description Cooking Oil Forms the Matrix of the Fatberg Cultivating Superbugs Unraveling the Hidden Dimension of Drug (Ab)Use Fatberg by the Sea Questions Biochemical Insights Final Discussion Selected Bibliography Part II: The Interplay and Regulation of Metabolism Chapter 4: Introduction to Metabolism 4.1 Consecutive Reactions Without Enzymes 4.2 Consecutive Reactions with Enzymes 4.2.1 The Bases of Enzymatic Catalysis and Its Impact in Metabolism Challenging Case 4.1: The Dark Side of Caffeine Source Case Description Background Information on Caffeine Facts and Figures About Caffeine: Abundant in Nature, Used and Abused by Humans Pharmacokinetics of Caffeine: Absorption, Distribution, and Metabolization Questions Biochemical Insight Final Discussion: Facts and Fantasies About Energy Drinks Challenging Case 4.2: Missing the Obvious … Twice! The Devil Is in the Details, so Is Recognition by Peers Sources Description Questions Biochemical Insights Final Discussion Challenging Case 4.3: Building Models in Metabolism, Descriptive, Predictive … Useful! Source Case Description Questions Biochemical Insight Final Discussion Fructose, Obesity, and Insulin Resistance A Suitable Energetic Substrate for a Tireless Cell Selected Bibliography Chapter 5: Regulation of Metabolisms 5.1 Levels of Regulation: Impact and Time Scale 5.2 Inhibition and Activation of Enzymes by Ligands 5.2.1 Nomenclature of Ligands 5.3 The Availability of Primary Precursors in a Metabolic Pathway 5.3.1 Transport of Metabolites and Effectors Across Membranes 5.4 Slower (But Efficient!) Mechanisms of Controlling Enzyme Action 5.5 Key Molecules in Energy Metabolism Challenging Case 5.1: Mushroom Poisons Starring on Stage and Science Source Case Description Questions Biochemical Insights Final Discussion Challenging Case 5.2: The Biochemistry of Zombies Source Case Description Questions Biochemical Insights Final Discussion Selected Bibliography Chapter 6: Energy Conservation in Metabolism: The Mechanisms of ATP Synthesis 6.1 ATP Synthesis by Substrate-Level Phosphorylation 6.1.1 A Historical Perspective of the Fermentation Process Discovery 6.1.2 An Overview of the ATP Synthesis by Substrate-Level Phosphorylation During Fermentation 6.1.3 Glucose Fermentation Reactions 6.2 ATP Synthesis Through Oxidative Phosphorylation 6.2.1 A Historical Perspective of the Understanding of Cellular Respiration 6.2.2 An Overview of Oxidative Phosphorylation Process 6.2.3 The Electron Transport System 6.2.3.1 The Sequence of Electron Transfer Between the Electron Carrier Groups 6.2.3.2 The Organization of the Respiratory Complexes in the Inner Mitochondrial Membrane 6.2.3.3 The Structure of the Electron-Transferring Components 6.2.4 The ATP Synthesis Through Oxidative Phosphorylation 6.2.4.1 The Structure of ATP Synthase 6.2.4.2 The Mechanism of ATP Synthesis by the ATP Synthase 6.2.5 Regulation of Oxidative Phosphorylation 6.2.5.1 Uncoupling Proteins: The Physiological Uncouplers 6.2.5.2 Production of Reactive Oxygen Species in Mitochondria Challenging Case 6.1: The Tragic Matter in Energy Management Source Case Description Questions Biochemical Insight Final Discussion Challenging Case 6.2: The Force Comes from Within Source Case Description Questions Biochemical Insights Final Discussion Challenging Case 6.3: A Curious Girl Has Fallen into a Mad World Source Case Description Questions Biochemical Insights Final Discussion Selected Bibliography Chapter 7: Catabolism of the Major Biomolecules 7.1 An Overview of Catabolism 7.2 Citric Acid Cycle: The Central Pathway for the Oxidation of the Three Classes of Nutrient Molecules 7.2.1 Citric Acid Cycle Reactions 7.2.2 Citric Acid Cycle as a Dynamic Pathway 7.2.3 A Historical Overview of CAC Discovery 7.2.4 Regulation of Citric Acid Cycle 7.3 Catabolism of Carbohydrates 7.3.1 Carbohydrate Oxidation Reactions 7.3.2 Regulation of Pyruvate Conversion to Acetyl-CoA 7.4 Catabolism of Lipids 7.4.1 TAG Mobilization and Fatty Acid Transport in the Bloodstream 7.4.2 Activation of Fatty Acids 7.4.3 Fatty Acid Transport into Mitochondria 7.4.4 β-Oxidation: The Pathway for Fatty Acid Degradation 7.4.4.1 Oxidation of Saturated Fatty Acids with Even Number of Carbons Atoms 7.4.4.2 Oxidation of Odd-Chain Fatty Acids 7.4.4.3 Oxidation of Unsaturated Fatty Acids 7.4.5 Regulation of Fatty Acid Oxidation 7.4.6 Fatty Acid Conversion to Ketone Bodies 7.5 Catabolism of Amino Acids 7.5.1 An Overview of the Amino Acid Catabolism 7.5.2 Amino Acid Metabolism in the Liver 7.5.2.1 Oxidative Deamination of the Amino Acids 7.5.2.2 Amino Acid Interconversion: The Transamination Reactions 7.5.2.3 Pathways for the Metabolism of the Amino Acid Carbon Skeletons 7.5.2.4 Synthesis of Urea for Nitrogen Excretion 7.5.3 Amino Acid Metabolism in Other Tissues Challenging Case 7.1: Into the Wilderness of Metabolic Deregulation Source Case Description Questions 7.6.4 Biochemical Insights Final Discussion Challenging Case 7.2: A Mystic Man with an Aura of Flowers Source Case Description Questions Biochemical Insights Final Discussion Selected Bibliography Chapter 8: Metabolic Responses to Hyperglycemia: Regulation and Integration of Metabolism in the Absorptive State 8.1 Glucose Sensing by Cells 8.2 Biosynthesis of Glycogen 8.2.1 Formation of UDP-Glucose 8.2.2 Reactions for the Initiation of Glycogen Synthesis from UDP-Glucose 8.2.3 Reactions for the Elongation of Glycogen Chain 8.2.4 Regulation of Glycogen Synthesis 8.3 Biosynthesis of Lipids 8.3.1 Synthesis of Fatty Acids 8.3.1.1 Reactions for Fatty Acid Synthesis 8.3.1.2 Origin of the Acetyl-CoA for the Fatty Acid Synthesis 8.3.1.3 Origin of NADPH for the Fatty Acid Synthesis 8.3.1.4 Regulation of Fatty Acid Synthesis 8.3.2 Synthesis of Triacylglycerols 8.4 Hormonal Responses to Hyperglycemia: Role of Insulin 8.4.1 Discovery of Insulin 8.4.2 Mechanisms of Insulin Action 8.4.3 Effects of Insulin on Energy Metabolism 8.4.3.1 Effects of Insulin on Glucose Uptake by Muscle and Adipose Tissue 8.4.3.2 Effects of Insulin on Metabolic Pathways 8.5 Metabolic Interplay in Response to Hyperglycemia Challenging Case 8.1: Beyond the Enigmatic Smile—The Occult Hyperlipidemia of Mona Lisa Source Case Description Questions Biochemical Insights Final Discussion Alcoholic Fatty Liver (AFL) HCV Infection Challenging Case 8.2: Dolores Bothered to Kill Her Dying Husband Source Case Description Questions Biochemical Insights Final Discussion Insulin as Weapon Insulin Concentration: Activity vs. Molar Concentration Insulin Sources Over Time Beyond Hyperinsulinemia-Induced Hypoglycemia Selected Bibliography Chapter 9: Regulation and Integration of Metabolism During Hypoglycemia 9.1 Overview of Metabolism During Fasting: Exemplifying with Studies on Therapeutic Starvation 9.2 Glycogen Degradation in the Liver 9.2.1 Reactions of Glycogen Degradation 9.2.2 Regulation of Glycogen Degradation in the Liver 9.3 Gluconeogenesis 9.3.1 Gluconeogenesis Reactions 9.3.2 Precursors for the Synthesis of Glucose 9.3.3 Regulation of Gluconeogenesis 9.3.4 Dynamic Utilization of Gluconeogenesis Precursors 9.4 Hormonal Responses to Hypoglycemia 9.4.1 Glucagon: Mechanism of Action and Effects on Energy Metabolism 9.4.1.1 Effects of Glucagon on Liver Metabolism 9.4.1.2 Effects of Glucagon on the Adipose Tissue 9.4.2 Glucocorticoids: Mechanism of Action and Effects on Energy Metabolism 9.4.2.1 Effects of Glucocorticoids on Muscle Metabolism 9.4.2.2 Effects of Glucocorticoids on Liver Metabolism Challenging Case 9.1: Kenny Faced the Fa(s)t Source Case Description Questions Biochemical Insight Final Discussion Challenging Case 9.2: The Lychee Paradox: Deliciously Sugary, Dangerously Hypoglycemiant Sources Description Questions Biochemical Insights Final Discussion Lychee Breeding and Lychee Overeating Challenging Case 9.3: The Bizarre Death of Elaine Robinson Source Case Description Questions Biochemical Insight Final Discussion Selected Bibliography Chapter 10: Regulation and Integration of Metabolism During Physical Activity 10.1 Muscle Contraction 10.1.1 Structural Organization of the Contractile Apparatus 10.1.1.1 The Main Proteic Components of the Contractile Apparatus 10.1.2 Mechanism of Muscle Contraction 10.1.2.1 The Sliding Filaments Model 10.1.3 Regulation of Muscle Contraction 10.2 Different Metabolic Profiles of the Skeletal Muscle Fibers 10.3 Overview of ATP Synthesis in the Muscle Cells 10.4 Muscle Cell Metabolism During Physical Activity 10.4.1 Role of the Cellular Energy Charge in the Muscle Cell Metabolism 10.4.1.1 The AMP-Activated Protein Kinase: A Cellular Energy Sensor 10.4.2 Metabolic Pathways for ATP Synthesis in the Skeletal Muscle 10.4.2.1 Fatty Acid Oxidation in Skeletal Muscle 10.4.2.2 Insulin-Independent Glucose Uptake in Skeletal Muscle 10.4.2.3 Glycogen Degradation in Skeletal Muscle 10.4.2.4 Glycolysis in Skeletal Muscle 10.5 Hormonal Regulation During Physical Activity: Role of Adrenaline 10.5.1 Molecular Mechanisms of Adrenaline Action 10.5.1.1 Cellular Receptors for Adrenaline 10.5.2 Effects of Adrenaline on Energy Metabolism 10.5.2.1 Effects of Adrenaline on the Adipose Tissue Metabolism 10.5.2.2 Effects of Adrenaline on the Liver Metabolism 10.5.2.3 Effects of Adrenaline on Muscle Metabolism Challenging Case 10.1: Iron Muscles—Men of Steel Source Case Description Questions Biochemical Insights Final Discussion Challenging Case 10.2: Armstrong’s Race to the Sun Sources Case Description Questions Biochemical Insights Final Discussion Challenging Case 10.3: K. V. Switzer’s Run for Rights Source Case Description Questions Biochemical Insights Final Discussion Selected Bibliography Chapter 11: Control of Body Weight and the Modern Metabolic Diseases 11.1 Humoral Control of Food Ingestion 11.1.1 A Historical Perspective of the Role of Hypothalamus in Food Intake 11.1.2 Leptin: A Hormone Indicative of Adiposity 11.1.3 Intestinal Peptides: Triggers of Postprandial Satiety 11.1.4 Ghrelin: The Main Orexigenic Hormone 11.1.5 The Arcuate Nucleus and the Melanocortin System 11.2 Control of Energy Expenditure 11.2.1 Adaptive Thermogenesis 11.2.1.1 Cold-Induced Thermogenesis 11.2.1.2 Diet-Induced Thermogenesis 11.2.2 Role of Thyroid Hormones 11.3 Obesity and the Metabolic Syndrome 11.3.1 Chronic Inflammation and Insulin Resistance in Obesity 11.3.2 Origin of Inflammation in Obesity Challenging Case 11.1: The Capsules of (H)eating Beauty Source Case Description Questions Biochemical Insights Final Discussion Anti-obesity Medications: Pharmacological Strategies for Obesity Control Challenging Case 11.2: Running to Eternity in Between Suet and Sweat Sources Case Description Questions Biochemical Insights Final Discussion Challenging Case 11.3: Malthus Meets Metabolism Sources Case Description Questions Biochemical Insights Final Discussion Selected Bibliography Credits Index