Biochemistry

Biochemistry Second Edition**,** is a single-semester text designed for undergraduate non-biochemistry majors. Accessible, engaging, and informative, it is the perfect introduction to the subject for students who may approach chemistry with apprehension. Its unique emphasis on metabolism and its kinetic underpinnings gives the text up-to-the-minute relevance for students investigating current public health concerns, such as obesity and diabetes. __Biochemistry Second Edition__ will encourage students to explore the basics of chemistry and its influence on biological problems. Key Features: * Provides an understanding of (mostly) enzymatic reactions that are responsible for the function and maintenance of living things. * This innovative text for non-biochemistry majors includes introductory material at the beginning of each chapter that contextualizes chapter themes in real-life scenarios. * Online supporting materials with further opportunities for research and investigation. * Synthesis questions at the end of each chapter that encourage students to make connections between concepts and ideas, as well as develop critical-thinking skills. Raymond S. Ochs is a biochemist with a career-long specialty in metabolism spanning 30 years. Previously, he has written the textbook __Biochemistry__, contributed the metabolism chapters to another text, __Principles of Biochemistry__, and co-edited a collection of articles published as __Metabolic Regulation__, and the recent monograph __Metabolic Strucure and Regulation__. His research interests concern major pathways of liver and muscle, including glycolysis, gluconeogenesis, ureogenesis, fatty acid metabolism, glycogen metabolism, and control by cAMP, Ca^2+^, diacylglycerol, and AMPK. He is currently professor of pharmacy at St. John’s University in New York, teaching biochemistry, physiology, and medicinal chemistry. Cover Half Title Title Page Copyright Page Dedication Table of Contents Preface to the First Edition Preface to the Second Edition Acknowledgments Author Glossary Chapter 1 Foundations 1.1 Origins of Biochemistry 1.2 Some Chemical Ideas 1.2.1 Reactions and Their Kinetic Description 1.2.1.1 Equilibrium 1.2.2 The Steady-State 1.3 Acid–Base Reactions 1.4 Redox 1.5 Energy 1.6 Cell Theory 1.7 Species Hierarchy and Evolution 1.8 Biological Systems Key Terms Bibliography Chapter 2 Water 2.1 Structure of Water 2.1.1 Gas Phase Water 2.1.2 Partial Charges and Electronegativity 2.1.3 Condensed Phase Water: Hydrogen Bonding 2.1.4 Hydrogen Bonding in Condensed Phase Water 2.2 The Hydrophobic Effect 2.3 Molecules Soluble in Water 2.4 High Heat Retention: The Unusual Specific Heat of Liquid Water 2.5 Ionization of Water 2.6 Some Definitions for the Study of Acids and Bases 2.7 The pH Scale 2.8 The Henderson–Hasselbalch Equation 2.9 Titration and Buffering Summary Review Questions Chapter 2 Addendum: The Dielectric Key Terms Bibliography Chapter 3 Lipids 3.1 Significance 3.2 Fatty Acids 3.3 Triacylglycerols 3.4 Phospholipids 3.5 Cholesterol 3.6 Lipid–Water Interactions of Amphipathic Molecules 3.7 Phospholipid Monolayers 3.8 Lipid Composition of Membranes 3.9 Water Permeability of Membranes and Osmosis Summary Review Questions Chapter 3 Addendum: Inverted Micelles Key Terms Bibliography Chapter 4 Carbohydrates 4.1 Monosaccharides 4.2 Ring Formation in Sugars 4.3 Disaccharides 4.4 Polysaccharides 4.4.1 Linear Polysaccharides 4.4.2 Branched Polysaccharides 4.5 Carbohydrate Derivatives 4.5.1 Simple Modifications 4.5.2 Substituted Carbohydrates Summary Review Questions Chapter 4 Addendum: The Discovery of Stereoisomerism Key Terms Bibliography Chapter 5 Amino Acids and Proteins 5.1 Common Structure of the Amino Acids 5.2 Biology of the Amino Acids 5.3 Amino Acid Individuality: The R Groups 5.3.1 Polarities 5.3.2 Functional Groups 5.4 Acid–Base Properties and Charge 5.4.1 Titration and Net Charge 5.4.2 Interactions between the α-Carboxylate and α-Amine Groups 5.4.2.1 Inductive Effect 5.4.2.2 Electric Field Effect 5.4.3 Multiple Dissociable Groups 5.5 The Peptide Bond 5.6 Peptides and Proteins 5.7 Levels of Protein Structure 5.7.1 Primary Structure 5.7.2 Secondary Structure 5.7.2.1 α-Helix 5.7.2.2 β-Sheet 5.7.3 Domains 5.7.4 Tertiary Structure 5.7.5 Quaternary Structure 5.8 Protein Folding 5.9 Oxygen Binding in Myoglobin and Hemoglobin 5.10 Other Binding Reactions Involving Proteins 5.10.1 Extracellular Binding Proteins 5.10.2 Cell Surface Binding Proteins 5.10.3 Intracellular Binding Proteins 5.11 Protein Purification and Analysis 5.11.1 Purification 5.11.2 Analysis Summary Review Questions Chapter 5 Addendum: Atomic Charged Forms Key Terms Bibliography Chapter 6 Enzymes 6.1 Energetics of Enzyme-Catalyzed Reactions 6.2 The Enzyme Assay and Initial Velocity 6.3 A Simple Kinetic Mechanism 6.3.1 Assumptions 6.3.2 The Michaelis–Menten Equation 6.4 How the Michaelis–Menten Equation Describes Enzyme Behavior 6.5 The Meaning of Km 6.6 Reversible Inhibition 6.6.1 Competitive Inhibition 6.6.2 Anticompetitive Inhibition (Uncompetitive) 6.6.3 Mixed Inhibition (Noncompetitive) 6.7 Double-Reciprocal or Lineweaver–Burk Plot 6.8 Allosteric Enzymes 6.9 Irreversible Inhibition 6.10 Enzyme Mechanisms 6.10.1 Nucleophilic Substitution 6.10.2 Acid–Base Catalysis 6.11 Enzyme Categories 6.12 Enzyme-Like Qualities of Membrane Transport Proteins Summary Review Questions Chapter 6 Addendum: The Haldane Relationship Key Terms Bibliography Chapter 7 Coenzymes 7.1 Coenzymes: Bound and Mobile 7.2 Coenzymes and Vitamins 7.3 Redox Coenzymes 7.3.1 Nicotinamides 7.3.2 Ubiquinone 7.3.3 Flavin Coenzymes 7.4 Acyl Transfers 7.4.1 CoA 7.4.2 Carnitine 7.4.3 Lipoic Acid 7.5 Carboxylation 7.5.1 Biotin 7.5.2 Vitamin K 7.6 Exchange Coenzymes 7.6.1 Thiamine Pyrophosphate 7.6.2 Pyridoxal Phosphate 7.7 Metal Ion Cofactors 7.7.1 Mg2+ 7.7.2 Iron 7.7.3 Copper 7.7.4 Co2+ 7.7.5 Mn2+and Zn2+ 7.7.6 Selenium 7.7.7 Dietary Essentials Review Questions Chapter 7 Addendum: The Vitamin K Cycle Key Terms Bibliography Chapter 8 Metabolism and Energy 8.1 Origins of Thermodynamics 8.2 First Law of Thermodynamics 8.2.1 Heat and Work 8.2.2 Enthalpy 8.3 Entropy and the Second Law of Thermodynamics 8.3.1 Entropy as a Ratio of Heat to Temperature 8.3.2 Entropy as a Statistical Distribution of States 8.4 Free Energy 8.5 Standard Free Energy 8.6 Nonstandard Free Energy Changes 8.7 Near-Equilibrium and Metabolically Irreversible Reactions 8.8 ATP 8.9 Energy Coupling with ATP 8.9.1 Creatine Phosphokinase 8.9.2 NDP Kinase 8.9.3 Adenylate Kinase 8.10 Energy of Redox Reactions 8.10.1 Electricity Fundamentals 8.10.2 The Electrochemical Cell 8.10.3 Standard Reduction Potentials 8.10.4 Reduction Potentials and Free Energy 8.10.5 Reduction Potentials 8.11 Mobile Cofactors and the Pathway View Summary Review Questions Chapter 8 Addendum: Free Energy Derivation Key Terms Bibliography Chapter 9 Glycolysis 9.1 Glucose Transport 9.2 From Glucose to Pyruvate 9.2.1 Hexokinase 9.2.2 Glucose Phosphate Isomerase 9.2.3 Phosphofructokinase 9.2.4 Aldolase 9.2.5 Triose Phosphate Isomerase 9.2.6 Glyceraldehyde Phosphate Dehydrogenase 9.2.7 Phosphoglycerate Kinase 9.2.8 Phosphoglycerate Mutase 9.2.9 Enolase 9.2.10 Pyruvate Kinase 9.3 Completing the Pathway 9.3.1 Lactate Formation 9.3.2 Ethanol Formation 9.4 Energetics of Glycolysis 9.4.1 Pathway Thermodynamics 9.4.2 Red Blood Cell Shunt Pathway 9.4.3 Arsenate Poisoning 9.4.4 Fructose Metabolism 9.4.5 Energy Balance and Glycolytic Connections 9.5 Metabolic Connections to Glycolysis 9.5.1 Alternative Entry Points 9.5.2 Glycolytic Intermediates as Intersection Points 9.5.3 Alternative Endpoints of Glycolysis Summary Review Questions Chapter 9 Addendum: Alternatives to Glycolysis Key Terms Bibliography Chapter 10 The Krebs Cycle 10.1 A Cyclic Pathway 10.2 Acetyl-CoA: Substrate of the Krebs Cycle 10.3 Overview of Carbon Flow 10.4 Steps of the Pathway 10.4.1 Citrate Synthase 10.4.2 Aconitase 10.4.3 Cis-Aconitate as a Krebs Cycle Intermediate 10.4.4 Prochirality 10.4.5 The R/S System of Nomenclature 10.4.6 Fluoroacetate Poisoning 10.4.7 Isocitrate DH 10.4.8 α-Ketoglutarate DH Complex 10.4.9 Succinyl-CoA Synthetase 10.4.10 Succinate DH 10.4.11 Fumarase 10.4.12 Malate DH 10.5 Energy Balance 10.6 Regulation 10.7 Krebs Cycle as a Second Crossroad of Metabolic Pathways Summary Review Questions Chapter 10 Addendum: Cyclic Pathways Connected to the Krebs Cycle 1. Glyoxylate Cycle 2. Itaconate Pathway Key Terms Bibliography Chapter 11 Oxidative Phosphorylation 11.1 The Phenomenon 11.2 Mitochondrial Inner Membrane 11.3 Carriers of Electrons, Protons, or Both 11.3.1 Carriers of Electrons 11.3.2 Carriers of Protons 11.3.3 Carriers of Both Electrons and Protons 11.4 Membrane-Bound Complexes 11.5 The Electrochemical Cell and the Mitochondria 11.6 Electron Pathways 11.6.1 Sequence of Electron Flow 11.6.2 Energetics of Electron Flow 11.7 Mechanisms of the Mitochondrial Membrane Protein Complexes 11.7.1 Complex I: Proton Pump 11.7.2 Complex II: Succinate Dehydrogenase 11.7.3 Complex III: Loop Mechanism 11.7.4 Complex IV: Pump and Annihilation 11.7.5 Complex V: ATP Synthesis 11.7.5.1 The Stator 11.7.5.2 The Rotor 11.8 Proton-Motive Force 11.8.1 Electric Circuit Analogy to the Proton Gradient 11.8.2 Utilization of Δp beyond ATP Synthesis 11.9 Mitochondrial Membrane Transport 11.9.1 Adenine Nucleotide Translocase 11.9.2 Phosphate Exchange 11.9.3 Other Transport Proteins 11.9.4 Coupling of Oxidation and Phosphorylation 11.10 Uncoupling 11.10.1 Physiological Uncoupling: Brown Fat 11.11 Superoxide Formation by Mitochondria 11.12 Control of Mitochondria 11.13 How Mitochondria Can Utilize Cytosolic NADH 11.13.1 Glycerol Phosphate Shuttle 11.13.2 Malate/Aspartate Shuttle Summary Review Questions Chapter 11 Addendum: Supercomplexes Key Terms Bibliography Chapter 12 Photosynthesis 12.1 Light and Carbon Reactions 12.2 Chloroplasts 12.2.1 Orientations: N and P Sides of the Membrane 12.2.2 Light Reactions of Photosynthesis as a Reversed Oxidative Phosphorylation 12.2.3 Carbon Reactions of Photosynthesis: CO2 Fixation 12.3 Harnessing Light Energy 12.3.1 Light Absorption and the Antennae 12.3.2 Electron Transfer at Reaction Centers 12.4 Proton and Electron Flow for the Light Reactions 12.5 Cyclic Electron Transfer and Other Variations 12.6 The Calvin Cycle 12.6.1 Ribulose Bisphosphate Carboxylase 12.6.2 Reaction Steps Following Carbon Fixation to Glyceraldehyde-P: Energy Consuming Portion 12.6.3 From GAP to the RuBP: Overview 12.6.4 From GAP to the RuBisCo Step: Reactions 12.7 Variations in CO2 Handling: C3, C4, and CAM Plants 12.8 Pathway Endpoints: Sucrose and Starch Summary Review Questions Chapter 12 Addendum: Dark vs Carbon Reactions Key Terms Bibliography Chapter 13 Carbohydrate Pathways Related to Glycolysis 13.1 Glycogen Metabolism 13.1.1 Glycogen Synthesis 13.1.2 Glycogenolysis 13.1.3 Physiological Context of Glycogen Metabolism 13.1.4 Regulation of Glycogen Metabolism by Glucagon 13.1.5 Regulation of Glycogen Metabolism by Epinephrine 13.1.6 Regulation of Glycogen Metabolism by Insulin 13.1.7 Regulation of Glycogen Metabolism by AMP Kinase 13.2 Gluconeogenesis 13.2.1 Lactate Dehydrogenase as a Gluconeogenic Enzyme 13.2.2 Pyruvate to PEP 13.2.3 Indirect Transport of Oxaloacetate from Mitochondria to Cytosol 13.2.4 Fructose-1,6-P2 to Fructose-6-P 13.2.5 Glucose-6-P to Glucose 13.2.6 Pathway Integration: Glycolysis, Glycogen Metabolism, and Gluconeogenesis 13.2.6.1 The Feeding–Fasting Transition 13.2.6.2 The Resting–Exercise Transition 13.3 The Pentose Phosphate Shunt 13.3.1 Oxidative Stage 13.3.2 Nonoxidative Stage 13.3.2.1 Reactions of the Nonoxidative Stage 13.3.2.2 A Pseudo Three-Dimensional View and Comparison to the Calvin Cycle 13.3.3 Distribution Between NADPH Production and Ribose-5-P 13.4 Galactose Utilization Summary Review Questions Chapter 13 Addendum: Phosphorylation of Glycogen Key Terms Bibliography Chapter 14 Lipid Metabolism 14.1 Absorption of Dietary Lipids 14.2 Fatty Acid Oxidation 14.2.1 Activation 14.2.2 Transport 14.2.3 β-Oxidation 14.2.3.1 Unsaturated Fatty Acids 14.2.3.2 Odd Carbon-Numbered Fatty Acids 14.2.3.3 Shorter and Longer Fatty Acids 14.3 Ketone Body Metabolism 14.4 Fatty Acid Biosynthesis 14.4.1 Export of Acetyl-CoA to the Cytosol 14.4.2 Carboxylation of Acetyl-CoA to Malonyl-CoA 14.4.3 Sequential Addition of Two-Carbon Fragments to Form Palmitate 14.4.3.1 Loading 14.4.3.2 Condensation 14.4.3.3 Reduction 14.4.3.4 Dehydration 14.4.3.5 Second Reduction 14.5 Triacylglycerol Formation 14.6 Phospholipid Metabolism 14.7 Cholesterol Metabolism 14.8 Other Lipids 14.8.1 Eicosanoids 14.8.2 Sphingolipids 14.8.3 Unusual Bacterial Fatty Acids 14.9 Overview of Lipid Metabolism in the Fed and Fasted States 14.10 Integration of Lipid and Carbohydrate Metabolism 14.10.1 Lipid and Carbohydrate Intersections in the Feeding–Fasting Transition 14.10.2 Lipid and Carbohydrate Intersections in the Resting–Exercise Transition 14.10.3 Lipid and Carbohydrate Intersections in Diabetes Mellitus Summary Review Questions Chapter 14 Addendum: The Isoprenes Key Terms Bibliography Chapter 15 Nitrogen Metabolism 15.1 The Nitrogen Cycle 15.2 Reaction Types in NH3 Assimilation 15.2.1 Redox-Neutral 15.2.2 Redox-Active 15.2.3 Redox-Balanced 15.3 Metabolically Irreversible Nitrogen Exchange Reactions 15.4 Near-Equilibrium Nitrogen Exchange Reactions 15.4.1 Glutamate DH 15.4.2 Transaminases 15.5 The Urea Cycle 15.5.1 [NH3] Exceeds [Aspartate] 15.5.2 [Aspartate] Exceeds [NH3] 15.5.3 Steps from NH3 to Citrulline 15.5.4 Cytosolic Steps of the Urea Cycle 15.5.5 Overall Urea Cycle 15.6 Amino Acid Metabolism: Catabolism 15.6.1 Branched-Chain Amino Acid Breakdown 15.6.2 Threonine 15.6.3 Lysine 15.6.4 Tryptophan 15.6.5 Phenylalanine and Tyrosine Degradation 15.6.6 Amino Acids Directly Connected to Major Metabolic Pathways 15.6.7 Arginine, Proline, and Histidine Are All Converted to Glutamate 15.6.8 One-Carbon (1C) Metabolism and Serine, Glycine, and Methionine Breakdown 15.7 Amino Acids: Anabolism 15.7.1 Nonessential Amino Acids 15.7.2 Essential Amino Acids 15.7.3 Aromatic Amino Acid Biosynthesis 15.8 Nucleotide Metabolism 15.8.1 Pyrimidine Synthesis 15.8.2 Pyrimidine Degradation 15.8.3 Purine Synthesis 15.8.4 Purine Degradation 15.8.5 Salvage Reactions 15.8.6 Purine Nucleotide Regulation 15.8.7 Purine Nucleotide Cycle 15.8.8 Deoxynucleotide Formation 15.8.9 A Unique Methylation to Form dTMP 15.9 Other Nitrogen Pathways Summary Review Questions Chapter 15 Addendum: Nitrogen Disposal The Tilapia of Lake Magadi The Alligator and the Crocodile Low Creatinine and Liver Failure Key Terms References Chapter 16 Nucleic Acids 16.1 Strand Structures of the Nucleic Acids 16.2 Structure of the Double Helix 16.3 Supercoiling 16.4 Histones 16.5 Replication 16.5.1 Initiation 16.5.2 Replication Fork and the Replisome 16.5.3 Primer Formation 16.5.4 Creating the Double Helix 16.5.5 Distinctive Features of Eukaryotic Replication 16.6 DNA Repair 16.6.1 Mismatch Repair 16.6.2 Excision Repair 16.6.3 PARP 16.7 Transcription 16.7.1 RNA Polymerase Binding to DNA 16.7.2 Transcription Events in E. coli 16.7.3 Eukaryotic Transcription Summary Review Questions Chapter 16 Addendum: Restriction Enzymes and PCR Restriction Enzymes PCR Key Terms Bibliography Chapter 17 Protein Synthesis and Degradation 17.1 Three Forms of RNA Employed in Protein Synthesis 17.1.1 tRNA 17.1.2 rRNA and the Ribosomes 17.2 The Genetic Code 17.3 Steps in Protein Synthesis 17.3.1 Initiation 17.3.2 Elongation 17.3.3 Termination 17.3.4 Distinctive Features of Eukaryotic Translation 17.3.5 Regulation of Eukaryotic Translation 17.4 Co-Translational and Post-Translational Modifications of Proteins 17.4.1 Co-Translational Modifications 17.4.2 Post-Translational Modifications 17.5 Protein Degradation 17.5.1 Extracellular Proteases 17.5.2 Intracellular Proteases 17.6 The mTOR Pathway in the Control of Protein Synthesis Summary Review Questions Chapter 17 Addendum: Skeletal Muscle and Exercise Key Terms Bibliography Appendix Index Biochemistry Second Edition , is a single-semester text designed for undergraduate non-biochemistry majors. Accessible, engaging, and informative, it is the perfect introduction to the subject for students who may approach chemistry with apprehension. Its unique emphasis on metabolism and its kinetic underpinnings gives the text up-to-the-minute relevance for students investigating current public health concerns, such as obesity and diabetes. Biochemistry Second Edition will encourage students to explore the basics of chemistry and its influence on biological problems. Key Features: Provides an understanding of (mostly) enzymatic reactions that are responsible for the function and maintenance of living things. This innovative text for non-biochemistry majors includes introductory material at the beginning of each chapter that contextualizes chapter themes in real-life scenarios. Online supporting materials with further opportunities for research and investigation. Synthesis questions at the end of each chapter that encourage students to make connections between concepts and ideas, as well as develop critical-thinking skills. About the Author: Raymond S. Ochs is a biochemist with a career-long specialty in metabolism spanning 30 years. Previously, he has written the textbook Biochemistry , contributed the metabolism chapters to another text, Principles of Biochemistry , and co-edited a collection of articles published as Metabolic Regulation , and the recent monograph Metabolic Strucure and Regulation . His research interests concern major pathways of liver and muscle, including glycolysis, gluconeogenesis, ureogenesis, fatty acid metabolism, glycogen metabolism, and control by cAMP, Ca 2+ , diacylglycerol, and AMPK. He is currently professor of pharmacy at St. John’s University in New York, teaching biochemistry, physiology, and medicinal chemistry.