Integrative Human Biochemistry: A Textbook for Medical Biochemistry

Description

This book covers in detail the mechanisms for how energy is managed in the human body. The basic principles that elucidate the reactivity and physical interactions of matter are addressed and quantified with simple approaches. Three-dimensional representations of molecules are presented throughout the book so molecules can be viewed as unique entities in their shape and function. The book is focused on the molecular mechanisms of cellular processes in the context of human physiological situations such as fasting, feeding and physical exercise, in which metabolic regulation is highlighted. Furthermore the book uses key historical experiments that opened up new concepts in Biochemistry to further illustrate how the human body functions at molecular level, helping students to appreciate how scientific knowledge emerges. This book also: · Elucidates the foundations of the molecular events of life · &nb sp; Uses key historical experiments that opened up new concepts in Biochemistry to further illustrate how the human body functions at molecular level, helping students to appreciate how scientific knowledge emerges · Provides realistic representations of molecules throughout the book Advance Praise for Integrative Human Biochemistry “This textbook provid es a modern and integrative perspective of human biochemistry and will be a faithful companion to health scie nce students following curricula in which this discipline is addressed. This textbook will be a most useful tool for the teaching community.” –Joan Guinovart Director of the Institute for Research in Biomedicine, Barcelona, Spain President-elect of the International Union of Biochemistry and Molecular Biology, IUBMB Dedication Foreword: Leopoldo De Meis’ Legacy—A Biochemistry Textbook with a Difference Preface Presentation of Book Structure 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 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 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 Monosaccharides 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 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 Basis of Enzymatic Catalysis and Its Impact in Metabolism Selected Bibliography Chapter 5: The 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 Slow (But Efficient!) Mechanisms of Controlling Enzyme Action 5.5 Key Molecules in Energy Metabolism Selected Bibliography Chapter 6: Energy Conservation in Metabolism: The Mechanisms of ATP Synthesis 6.1 Fermentation: The Anaerobic Pathway for ATP Synthesis 6.1.1 A Historical Perspective of the Discovery of the Fermentation Process 6.1.2 An Overview of the ATP Synthesis by Substrate-Level Phosphorylation During Fermentation 6.1.3 Glucose Fermentation Reactions 6.2 Oxidative Phosphorylation: The Main Mechanism of ATP Synthesis in Most Human Cells 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 Selected Bibliography Chapter 7: Catabolism of the Major Biomolecules 7.1 An Overview of Catabolism 7.2 Tricarboxylic Acid Cycle: The Central Pathway for the Oxidation of the Three Classes of Nutrient Molecules 7.2.1 TCA Cycle Reactions 7.2.2 TCA Cycle as a Dynamic Pathway 7.2.3 A Historical Overview of the TCA Cycle Discovery 7.2.4 Regulation of the TCA 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 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 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 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 the Skeletal Muscle 10.4.2.3 Glycogen Degradation in the Skeletal Muscle 10.4.2.4 Glycolysis in the 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 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 Selected Bibliography Credits Index