Biochemistry: Concepts and Connections, Global Edition
Höfundar: Dean R Appling, Spencer J. Anthony-Cahill, Christopher K. Mathews
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Time limit The eBooks products do not have an expiry date. You will continue to access your digital ebook products whilst you have your Bookshelf installed. For one or two semester biochemistry courses (science majors). A highly visual, precise and fresh approach to guide today’s mixed-science majors to a deeper understanding of biochemistry Biochemistry: Concepts and Connections engages students in the rapidly evolving field of biochemistry, better preparing them for the challenges of 21st century science through quantitative reasoning skills and a rich, chemical perspective on biological processes.
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- Höfundar: Dean R Appling, Spencer J. Anthony-Cahill, Christopher K. Mathews
- Útgáfa:2
- Útgáfudagur: 2019-02-07
- Hægt að prenta út 2 bls.
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- Format:Page Fidelity
- ISBN 13: 9781292267302
- Print ISBN: 9781292267203
- ISBN 10: 1292267305
Efnisyfirlit
- Title Page
- Copyright Page
- Brief Contents
- Contents
- Preface
- Acknowledgments for the Global Edition
- About the Authors
- Tools of Biochemistry
- Foundation Figures
- Chapter 1: Biochemistry and the Language of Chemistry
- 1.1. The Science of Biochemistry
- The Origins of Biochemistry
- The Tools of Biochemistry
- Biochemistry as a Discipline and an Interdisciplinary Science
- 1.2. The Elements and Molecules of Living Systems
- The Chemical Elements of Cells and Organisms
- The Origin of Biomolecules and Cells
- The Complexity and Size of Biological Molecules
- The Biopolymers: Proteins, Nucleic Acids, and Carbohydrates
- Lipids and Membranes
- 1.3. Distinguishing Characteristics of Living Systems
- 1.4. The Unit of Biological Organization: The Cell
- 1.5. Biochemistry and the Information Explosion
- 1.1. The Science of Biochemistry
- Chapter 2: The Chemical Foundation of Life: Weak Interactions in an Aqueous Environment
- 2.1. The Importance of Noncovalent Interactions in Biochemistry
- 2.2. The Nature of Noncovalent Interactions
- Charge–Charge Interactions
- Dipole and Induced Dipole Interactions
- Van der Waals Interactions
- Hydrogen Bonds
- 2.3. The Role of Water in Biological Processes
- The Structure and Properties of Water
- Water as a Solvent
- Ionic Compounds in Aqueous Solution
- Hydrophilic Molecules in Aqueous Solution
- Hydrophobic Molecules in Aqueous Solution
- Amphipathic Molecules in Aqueous Solution
- 2.4. Acid–Base Equilibria
- Acids and Bases: Proton Donors and Acceptors
- Ionization of Water and the Ion Product
- The pH Scale and the Physiological pH Range
- Weak Acid and Base Equilibria: Ka and pKa
- Titration of Weak Acids: The Henderson–Hasselbalch Equation
- Buffer Solutions
- Molecules with Multiple Ionizing Groups
- 2.5. Interactions Between Macroions in Solution
- Solubility of Macroions and pH
- The Influence of Small Ions: Ionic Strength
- Tools of Biochemistry: 2A Electrophoresis and Isoelectric Focusing
- Foundation Figure: Biomolecules: Structure and Function
- 3.1. Free Energy
- Thermodynamic Systems
- The First Law of Thermodynamics and Enthalpy
- The Driving Force for a Process
- Entropy
- The Second Law of Thermodynamics
- 3.2. Free Energy: The Second Law in Open Systems
- Free Energy Defined in Terms of Enthalpy and Entropy Changes in the System
- An Example of the Interplay of Enthalpy and Entropy: The Transition Between Liquid Water and Ice
- The Interplay of Enthalpy and Entropy: A Summary
- Free Energy and Useful Work
- 3.3. The Relationships Between Free Energy, the Equilibrium State, and Nonequilibrium Concentrations
- Equilibrium, Le Chatelier’s Principle, and the Standard State
- Changes in Concentration and .G
- .G versus .G°, Q versus K, and Homeostasis versus Equilibrium
- Water, H+ in Buffered Solutions, and the “Biochemical Standard State”
- 3.4. Free Energy in Biological Systems
- Organic Phosphate Compounds as Energy Transducers
- Phosphoryl Group Transfer Potential
- Free Energy and Concentration Gradients: A Close Look at Diffusion Through a Membrane
- .G and Oxidation/Reduction Reactions in Cells
- Quantification of Reducing Power: Standard Reduction Potential
- Standard Free Energy Changes in Oxidation–Reduction Reactions
- Calculating Free Energy Changes for Biological Oxidations under Nonequilibrium Conditions
- A Brief Overview of Free Energy Changes in Cells
- 4.1. Nucleic Acids— Informational Macromolecules
- The Two Types of Nucleic Acid: DNA and RNA
- Properties of the Nucleotides
- Stability and Formation of the Phosphodiester Linkage
- 4.2. Primary Structure of Nucleic Acids
- The Nature and Significance of Primary Structure
- DNA as the Genetic Substance: Early Evidence
- 4.3. Secondary and Tertiary Structures of Nucleic Acids
- The DNA Double Helix
- Data Leading Toward the Watson–Crick Double-Helix Model
- X-Ray Analysis of DNA Fibers
- Semiconservative Nature of DNA Replication
- Alternative Nucleic Acid Structures: B and A Helices
- DNA and RNA Molecules in Vivo
- DNA Molecules
- Circular DNA and Supercoiling
- Single-Stranded Polynucleotides
- 4.4. Alternative Secondary Structures of DNA
- Left-Handed DNA (Z-DNA)
- Hairpins and Cruciforms
- Triple Helices
- G-Quadruplexes
- 4.5. The Helix-to-Random Coil Transition: Nucleic Acid Denaturation
- 4.6. The Biological Functions of Nucleic Acids: A Preview of Genetic Biochemistry
- Genetic Information Storage: The Genome
- Replication: DNA to DNA
- Transcription: DNA to RNA
- Translation: RNA to Protein
- Tools of Biochemistry: 4A Manipulating DNA
- Tools of Biochemistry: 4B An Introduction to X-Ray Diffraction
- 5.1. Amino Acids
- Structure of the a-Amino Acids
- Stereochemistry of the a-Amino Acids
- Properties of Amino Acid Side Chains: Classes of a-Amino Acids
- Amino Acids with Nonpolar Aliphatic Side Chains
- Amino Acids with Nonpolar Aromatic Side Chains
- Amino Acids with Polar Side Chains
- Amino Acids with Positively Charged (Basic) Side Chains
- Amino Acids with Negatively Charged (Acidic) Side Chains
- Rare Genetically Encoded Amino Acids
- Modified Amino Acids
- 5.2. Peptides and the Peptide Bond
- The Structure of the Peptide Bond
- Stability and Formation of the Peptide Bond
- Peptides
- Polypeptides as Polyampholytes
- 5.3. Proteins: Polypeptides of Defined Sequence
- 5.4. From Gene to Protein
- The Genetic Code
- Posttranslational Processing of Proteins
- 5.5. From Gene Sequence to Protein Function
- 5.6. Protein Sequence Homology
- Tools of Biochemistry: 5A Protein Expression and Purification
- Tools of Biochemistry: 5B Mass, Sequence, and Amino Acid Analyses of Purified Proteins
- 6.1. Secondary Structure: Regular Ways to Fold the Polypeptide Chain
- Theoretical Descriptions of Regular Polypeptide Structures
- a Helices and ß Sheets
- Describing the Structures: Helices and Sheets
- Amphipathic Helices and Sheets
- Ramachandran Plots
- 6.2. Fibrous Proteins: Structural Materials of Cells and Tissues
- The Keratins
- Fibroin
- Collagen
- 6.3. Globular Proteins: Tertiary Structure and Functional Diversity
- Different Folding for Different Functions
- Different Modes of Display Aid Our Understanding of Protein Structure
- Varieties of Globular Protein Structure: Patterns of Main-Chain Folding
- 6.4. Factors Determining Secondary and Tertiary Structure
- The Information for Protein Folding
- The Thermodynamics of Folding
- Conformational Entropy
- Charge–Charge Interactions
- Internal Hydrogen Bonds
- Van der Waals Interactions
- The Hydrophobic Effect
- Disulfide Bonds and Protein Stability
- Prosthetic Groups, Ion-Binding, and Protein Stability
- 6.5. Dynamics of Globular Protein Structure
- Kinetics of Protein Folding
- The “Energy Landscape” Model of Protein Folding
- Intermediate and Off-Pathway States in Protein Folding
- Chaperones Faciliate Protein Folding in Vivo
- Protein Misfolding and Disease
- 6.6. Prediction of Protein Secondary and Tertiary Structure
- Prediction of Secondary Structure
- Tertiary Structure Prediction: Computer Simulation of Folding
- 6.7. Quaternary Structure of Proteins
- Symmetry in Multisubunit Proteins: Homotypic Protein–Protein Interactions
- Heterotypic Protein–Protein Interactions
- Tools of Biochemistry: 6A Spectroscopic Methods for Studying Macromolecular Conformation in Solution
- Tools of Biochemistry: 6B Determining Molecular Masses and the Number of Subunits in a Protein Molec
- Foundation Figure: Protein Structure and Function
- 7.1. Binding a Specific Target: Antibody Structure and Function
- 7.2. The Adaptive Immune Response
- 7.3. The Structure of Antibodies
- 7.4. Antibody:Antigen Interactions
- Shape and Charge Complementarity
- Generation of Antibody Diversity
- 7.5. The Immunoglobulin Superfamily
- 7.6. The Challenge of Developing an AIDS Vaccine
- 7.7. Antibodies and Immunoconjugates as Potential Cancer Treatments
- 7.8. Oxygen Transport from Lungs to Tissues: Protein Conformational Change Enhances Function
- 7.9. The Oxygen-Binding Sites in Myoglobin and Hemoglobin
- Analysis of Oxygen Binding by Myoglobin
- 7.10. The Role of Conformational Change in Oxygen Transport
- Cooperative Binding and Allostery
- Models for the Allosteric Change in Hemoglobin
- Changes in Hemoglobin Structure Accompanying Oxygen Binding
- A Closer Look at the Allosteric Change in Hemoglobin
- 7.11. Allosteric Effectors of Hemoglobin Promote Efficient Oxygen Delivery to Tissues
- Response to pH Changes: The Bohr Effect
- Carbon Dioxide Transport
- Response to Chloride Ion at the a-Globin N-Terminus
- 2,3-Bisphosphoglycerate
- 7.12. Myoglobin and Hemoglobin as Examples of the Evolution of Protein Function
- The Structure of Eukaryotic Genes: Exons and Introns
- 7.13. Mechanisms of Protein Mutation
- Substitution of DNA Nucleotides
- Nucleotide Deletions or Insertions
- Gene Duplications and Rearrangements
- Evolution of the Myoglobin–Hemoglobin Family of Proteins
- 7.14. Hemoglobin Variants and Their Inheritance: Genetic Diseases
- Pathological Effects of Variant Hemoglobins
- 7.15. Protein Function Requiring Large Conformational Changes: Muscle Contraction
- 7.16. Actin and Myosin
- Actin
- Myosin
- 7.17. The Structure of Muscle
- 7.18. The Mechanism of Contraction
- Regulation of Contraction: The Role of Calcium
- Tools of Biochemistry: 7A Immunological Methods
- 8.1. Enzymes As Biological Catalysts
- 8.2. The Diversity of Enzyme Function
- 8.3. Chemical Reaction Rates and the Effects of Catalysts
- Reaction Rates, Rate Constants, and Reaction Order
- First-Order Reactions
- Second-Order Reactions
- Transition States and Reaction Rates
- Transition State Theory Applied to Enzymatic Catalysis
- 8.4. How Enzymes Act as Catalysts: Principles and Examples
- Models for Substrate Binding and Catalysis
- Mechanisms for Achieving Rate Acceleration
- Case Study #1: Lysozyme
- Case Study #2: Chymotrypsin, a Serine Protease
- 8.5. Coenzymes, Vitamins, and Essential Metals
- Coenzyme Function in Catalysis
- Metal Ions in Enzymes
- 8.6. The Kinetics of Enzymatic Catalysis
- Reaction Rate for a Simple Enzyme-Catalyzed Reaction: Michaelis–Menten Kinetics
- Interpreting KM, kcat, and kcat/KM
- Enzyme Mutants May Affect kcat and KM Differently
- Analysis of Kinetic Data: Testing the Michaelis–Menten Model
- 8.7. Enzyme Inhibition
- Reversible Inhibition
- Competitive Inhibition
- Uncompetitive Inhibition
- Mixed Inhibition
- Irreversible Inhibition
- Multisubstrate Reactions
- Random Substrate Binding
- Ordered Substrate Binding
- The Ping-Pong Mechanism
- Qualitative Interpretation of KM and Vmax: Application to Multisubstrate Reaction Mechanisms
- 8.8. The Regulation of Enzyme Activity
- Substrate-Level Control
- Feedback Control
- Allosteric Enzymes
- Homoallostery
- Heteroallostery
- Aspartate Carbamoyltransferase: An Example of an Allosteric Enzyme
- 8.9. Covalent Modifications Used to Regulate Enzyme Activity
- Pancreatic Proteases: Activation by Irreversible Protein Backbone Cleavage
- 8.10. Nonprotein Biocatalysts: Catalytic Nucleic Acids
- Tools of Biochemistry: 8A How to Measure the Rates of Enzyme-Catalyzed Reactions
- Foundation Figure: Regulation of Enzyme Activity
- 9.1. Monosaccharides
- Aldoses and Ketoses
- Enantiomers
- Alternative Designations for Enantiomers: d–l and R–S
- Monosaccharide Enantiomers in Nature
- Diastereomers
- Tetrose Diastereomers
- Pentose Diastereomers
- Hexose Diastereomers
- Aldose Ring Structures
- Pentose Rings
- Hexose Rings
- Sugars with More Than Six Carbons
- 9.2. Derivatives of the Monosaccharides
- Phosphate Esters
- Lactones and Acids
- Alditols
- Amino Sugars
- Glycosides
- 9.3. Oligosaccharides
- Oligosaccharide Structures
- Distinguishing Features of Different Disaccharides
- Writing the Structure of Disaccharides
- Stability and Formation of the Glycosidic Bond
- 9.4. Polysaccharides
- Storage Polysaccharides
- Structural Polysaccharides
- Cellulose
- Chitin
- Glycosaminoglycans
- The Proteoglycan Complex
- Nonstructural Roles of Glycosaminoglycans
- Bacterial Cell Wall Polysaccharides; Peptidoglycan
- 9.5. Glycoproteins
- N-Linked and O-Linked Glycoproteins
- N-Linked Glycans
- O-Linked Glycans
- Blood Group Antigens
- Erythropoetin: A Glycoprotein with Both O- and N-Linked Oligosaccharides
- Influenza Neuraminidase, a Target for Antiviral Drugs
- Tools of Biochemistry: 9A The Emerging Field of Glycomics
- 10.1. The Molecular Structure and Behavior of Lipids
- Fatty Acids
- Triacylglycerols: Fats
- Soaps and Detergents
- Waxes
- 10.2. The Lipid Constituents of Biological Membranes
- Glycerophospholipids
- Sphingolipids and Glycosphingolipids
- Glycoglycerolipids
- Cholesterol
- 10.3. The Structure and Properties of Membranes and Membrane Proteins
- Motion in Membranes
- Motion in Synthetic Membranes
- Motion in Biological Membranes
- The Asymmetry of Membranes
- Characteristics of Membrane Proteins
- Insertion of Proteins into Membranes
- Evolution of the Fluid Mosaic Model of Membrane Structure
- 10.4. Transport Across Membranes
- The Thermodynamics of Transport
- Nonmediated Transport: Diffusion
- Facilitated Transport: Accelerated Diffusion
- Carriers
- Permeases
- Pore-Facilitated Transport
- Ion Selectivity and Gating
- Active Transport: Transport Against a Concentration Gradient
- 10.5. Ion Pumps: Direct Coupling of ATP Hydrolysis to Transport
- 10.6. Ion Transporters and Disease
- 10.7. Cotransport Systems
- 10.8. Excitable Membranes, Action Potentials, and Neurotransmission
- The Resting Potential
- The Action Potential
- Toxins and Neurotransmission
- Foundation Figure: Targeting Pain and Inflammation through Drug Design
- 11.1. A First Look at Metabolism
- 11.2. Freeways on the Metabolic Road Map
- Central Pathways of Energy Metabolism
- Distinct Pathways for Biosynthesis and Degradation
- 11.3. Biochemical Reaction Types
- Nucleophilic Substitutions
- Nucleophilic Additions
- Carbonyl Condensations
- Eliminations
- Oxidations and Reductions
- 11.4. Bioenergetics of Metabolic Pathways
- Oxidation as a Metabolic Energy Source
- Biological Oxidations: Energy Release in Small Increments
- Energy Yields, Respiratory Quotients, and Reducing Equivalents
- ATP as a Free Energy Currency
- Metabolite Concentrations and Solvent Capacity
- Thermodynamic Properties of ATP
- The Important Differences Between .G and .G°
- Kinetic Control of Substrate Cycles
- Other High-Energy Phosphate Compounds
- Other High-Energy Nucleotides
- Adenylate Energy Charge
- 11.5. Major Metabolic Control Mechanisms
- Control of Enzyme Levels
- Control of Enzyme Activity
- Compartmentation
- Hormonal Regulation
- Distributive Control of Metabolism
- 11.6 Experimental Analysis of Metabolism
- Goals of the Study of Metabolism
- Levels of Organization at Which Metabolism Is Studied
- Whole Organisms
- Isolated or Perfused Organs
- Whole Cells
- Cell-Free Systems
- Purified Components
- Systems Level
- Metabolic Probes
- Tools of Biochemistry: 11A Metabolomics
- Tools of Biochemistry: 11B Radioactive and Stable Isotopes
- Foundation Figure: Enzyme Kinetics and Drug Action
- 12.1. An Overview of Glycolysis
- Relation of Glycolysis to Other Pathways
- Anaerobic and Aerobic Glycolysis
- Chemical Strategy of Glycolysis
- 12.2. Reactions of Glycolysis
- Reactions 1–5: The Energy Investment Phase
- Reaction 1: The First ATP Investment
- Reaction 2: Isomerization of Glucose-6-Phosphate
- Reaction 3: The Second Investment of ATP
- Reaction 4: Cleavage to Two Triose Phosphates
- Reaction 5: Isomerization of Dihydroxyacetone Phosphate
- Reactions 6–10: The Energy Generation Phase
- Reaction 6: Generation of the First Energy-Rich Compound
- Reaction 7: The First Substrate-Level Phosphorylation
- Reaction 8: Preparing for Synthesis of the Next High-Energy Compound
- Reaction 9: Synthesis of the Second High-Energy Compound
- Reaction 10: The Second Substrate-Level Phosphorylation
- 12.3. Metabolic Fates of Pyruvate
- Lactate Metabolism
- Isozymes of Lactate Dehydrogenase
- Ethanol Metabolism
- 12.4. Energy and Electron Balance Sheets
- 12.5. Gluconeogenesis
- Physiological Need for Glucose Synthesis in Animals
- Enzymatic Relationship of Gluconeogenesis to Glycolysis
- Bypass 1: Conversion of Pyruvate to Phosphoenolpyruvate
- Bypass 2: Conversion of Fructose-1,6-bisphosphate to Fructose-6-phosphate
- Bypass 3: Conversion of Glucose-6-phosphate to Glucose
- Stoichiometry and Energy Balance of Gluconeogenesis
- Gluconeogenesis
- Reversal of Glycolysis
- Substrates for Gluconeogenesis
- Lactate
- Amino Acids
- Ethanol Consumption and Gluconeogenesis
- 12.6. Coordinated Regulation of Glycolysis and Gluconeogenesis
- The Pasteur Effect
- Reciprocal Regulation of Glycolysis and Gluconeogenesis
- Regulation at the Phosphofructokinase/ Fructose-1,6-Bisphosphatase Substrate Cycle
- Fructose-2,6-bisphosphate and the Control of Glycolysis and Gluconeogenesis
- Regulation at the Pyruvate Kinase/Pyruvate Carboxylase + PEPCK Substrate Cycle
- Regulation at the Hexokinase/Glucose-6-Phosphatase Substrate Cycle
- 12.7. Entry of Other Sugars into the Glycolytic Pathway
- Monosaccharide Metabolism
- Galactose Utilization
- Fructose Utilization
- Disaccharide Metabolism
- Glycerol Metabolism
- Polysaccharide Metabolism
- Hydrolytic and Phosphorolytic Cleavages
- Starch and Glycogen Digestion
- 12.8. Glycogen Metabolism in Muscle and Liver
- Glycogen Breakdown
- Glycogen Biosynthesis
- Biosynthesis of UDP-Glucose
- The Glycogen Synthase Reaction
- Formation of Branches
- 12.9. Coordinated Regulation of Glycogen Metabolism
- Structure of Glycogen Phosphorylase
- Control of Phosphorylase Activity
- Proteins in the Glycogenolytic Cascade
- Cyclic AMP–Dependent Protein Kinase
- Phosphorylase b Kinase
- Calmodulin
- Nonhormonal Control of Glycogenolysis
- Control of Glycogen Synthase Activity
- Congenital Defects of Glycogen Metabolism in Humans
- 12.10. A Biosynthetic Pathway That Oxidizes Glucose: The Pentose Phosphate Pathway
- The Oxidative Phase: Generating Reducing Power as NADPH
- The Nonoxidative Phase: Alternative Fates of Pentose Phosphates
- Production of Six-Carbon and Three-Carbon Sugar Phosphates
- Tailoring the Pentose Phosphate Pathway to Specific Needs
- Regulation of the Pentose Phosphate Pathway
- Human Genetic Disorders Involving Pentose Phosphate Pathway Enzymes
- 13.1. Overview of Pyruvate Oxidation and the Citric Acid Cycle
- The Three Stages of Respiration
- Chemical Strategy of the Citric Acid Cycle
- Discovery of the Citric Acid Cycle
- 13.2. Pyruvate Oxidation: A Major Entry Route for Carbon into the Citric Acid Cycle
- Overview of Pyruvate Oxidation and the Pyruvate Dehydrogenase Complex
- Coenzymes Involved in Pyruvate Oxidation and the Citric Acid Cycle
- Thiamine Pyrophosphate (TPP)
- Lipoic Acid (Lipoamide)
- Coenzyme A: Activation of Acyl Groups
- Flavin Adenine Dinucleotide (FAD)
- Nicotinamide Adenine Dinucleotide (NAD+)
- Action of the Pyruvate Dehydrogenase Complex
- 13.3. The Citric Acid Cycle
- Step 1: Introduction of Two Carbon Atoms as Acetyl-CoA
- Step 2: Isomerization of Citrate
- Step 3: Conservation of the Energy Released by an Oxidative Decarboxylation in the Reduced Electron
- Step 4: Conservation of Energy in NADH by a Second Oxidative Decarboxylation
- Step 5: A Substrate-Level Phosphorylation
- Step 6: A Flavin-Dependent Dehydrogenation
- Step 7: Hydration of a Carbon–Carbon Double Bond
- Step 8: An Oxidation that Regenerates Oxaloacetate
- 13.4. Stoichiometry and Energetics of the Citric Acid Cycle
- 13.5. Regulation of Pyruvate Dehydrogenase and the Citric Acid Cycle
- Control of Pyruvate Oxidation
- Control of the Citric Acid Cycle
- 13.6. Organization and Evolution of the Citric Acid Cycle
- 13.7. Citric Acid Cycle Malfunction as a Cause of Human Disease
- 13.8. Anaplerotic Sequences: The Need to Replace Cycle Intermediates
- Reactions that Replenish Oxaloacetate
- The Malic Enzyme
- Reactions Involving Amino Acids
- 13.9. The Glyoxylate Cycle: An Anabolic Variant of the Citric Acid Cycle
- Tools of Biochemistry: 13A Detecting and Analyzing Protein–Protein Interactions
- 14.1. The Mitochondrion: Scene of the Action
- 14.2. Free Energy Changes in Biological Oxidations
- 14.3. Electron Transport
- Electron Carriers in the Respiratory Chain
- Flavoproteins
- Iron–Sulfur Proteins
- Coenzyme Q
- Cytochromes
- Respiratory Complexes
- NADH–Coenzyme Q Reductase (Complex I)
- Succinate–Coenzyme Q Reductase (Complex II; Succinate Dehydrogenase)
- Coenzyme Q:Cytochrome c Oxidoreductase (Complex III)
- Cytochrome c Oxidase (Complex IV)
- 14.4. Oxidative Phosphorylation
- The P/O Ratio: Energetics of Oxidative Phosphorylation
- Oxidative Reactions That Drive ATP Synthesis
- Mechanism of Oxidative Phosphorylation: Chemiosmotic Coupling
- A Closer Look at Chemiosmotic Coupling: The Experimental Evidence
- Membranes Can Establish Proton Gradients
- An Intact Inner Membrane Is Required for Oxidative Phosphorylation
- Key Electron Transport Proteins Span the Inner Membrane
- Uncouplers Act by Dissipating the Proton Gradient
- Generation of a Proton Gradient Permits ATP Synthesis Without Electron Transport
- Complex V: The Enzyme System for ATP Synthesis
- Discovery and Reconstitution of ATP Synthase
- Structure of the Mitochondrial F1ATP Synthase Complex
- Mechanism of ATP Synthesis
- 14.5. Respiratory States and Respiratory Control
- 14.6. Mitochondrial Transport Systems
- Transport of Substrates and Products into and out of Mitochondria
- Shuttling Cytoplasmic Reducing Equivalents into Mitochondria
- 14.7. Energy Yields from Oxidative Metabolism
- 14.8. The Mitochondrial Genome, Evolution, and Disease
- 14.9. Oxygen as a Substrate for Other Metabolic Reactions
- Oxidases and Oxygenases
- Cytochrome P450 Monooxygenase
- Reactive Oxygen Species, Antioxidant Defenses, and Human Disease
- Formation of Reactive Oxygen Species
- Dealing with Oxidative Stress
- Foundation Figure: Intermediary Metabolism
- 15.1. The Basic Processes of Photosynthesis
- 15.2. The Chloroplast
- 15.3. The Light Reactions
- Absorption of Light: The Light-Harvesting System
- The Energy of Light
- The Light-Absorbing Pigments
- The Light-Gathering Structures
- Photochemistry in Plants and Algae: Two Photosystems in Series
- Photosystem II: The Splitting of Water
- Photosystem I: Production of NADPH
- Summation of the Two Systems: The Overall Reaction and NADPH and ATP Generation
- An Alternative Light Reaction Mechanism: Cyclic Electron Flow
- Reaction Center Complexes in Photosynthetic Bacteria
- Evolution of Photosynthesis
- 15.4. The Carbon Reactions: The Calvin Cycle
- Stage I: Carbon Dioxide Fixation and Sugar Production
- Incorporation of CO2 into a Three-Carbon Sugar
- Formation of Hexose Sugars
- Stage II: Regeneration of the Acceptor
- 15.5. A Summary of the Light and Carbon Reactions in Two-System Photosynthesis
- The Overall Reaction and the Efficiency of Photosynthesis
- Regulation of Photosynthesis
- 15.6. Photorespiration and the C4 Cycle
- Part I: Bioenergetic Aspects of Lipid Metabolism
- 16.1. Utilization and Transport of Fat and Cholesterol
- Fats as Energy Reserves
- Fat Digestion and Absorption
- Transport of Fat to Tissues: Lipoproteins
- Classification and Functions of Lipoproteins
- Transport and Utilization of Lipoproteins
- Cholesterol Transport and Utilization in Animals
- The LDL Receptor and Cholesterol Homeostasis
- Cholesterol, LDL, and Atherosclerosis
- Mobilization of Stored Fat for Energy Generation
- 16.2. Fatty Acid Oxidation
- Early Experiments
- Fatty Acid Activation and Transport into Mitochondria
- The ß-Oxidation Pathway
- Reaction 1: The Initial Dehydrogenation
- Reactions 2 and 3: Hydration and Dehydrogenation
- Reaction 4: Thiolytic Cleavage
- Mitochondrial ß-Oxidation Involves Multiple Isozymes
- Energy Yield from Fatty Acid Oxidation
- Oxidation of Unsaturated Fatty Acids
- Oxidation of Fatty Acids with Odd-Numbered Carbon Chains
- Control of Fatty Acid Oxidation
- Ketogenesis
- 16.3. Fatty Acid Biosynthesis
- Relationship of Fatty Acid Synthesis to Carbohydrate Metabolism
- Early Studies of Fatty Acid Synthesis
- Biosynthesis of Palmitate from Acetyl-CoA
- Synthesis of Malonyl-CoA
- Malonyl-CoA to Palmitate
- Multifunctional Proteins in Fatty Acid Synthesis
- Transport of Acetyl Units and Reducing Equivalents into the Cytosol
- Elongation of Fatty Acid Chains
- Fatty Acid Desaturation
- Control of Fatty Acid Synthesis
- 16.4. Biosynthesis of Triacylglycerols
- Part II: Metabolism of Membrane Lipids, Steroids, and Other Complex Lipids
- 16.5. Glycerophospholipids
- 16.6. Sphingolipids
- 16.7. Steroid Metabolism
- Steroids: Some Structural Considerations
- Biosynthesis of Cholesterol
- Early Studies of Cholesterol Biosynthesis
- Stage 1: Formation of Mevalonate
- Stage 2: Synthesis of Squalene from Mevalonate
- Stage 3: Cyclization of Squalene to Lanosterol and Its Conversion to Cholesterol
- Control of Cholesterol Biosynthesis
- Cholesterol Derivatives: Bile Acids, Steroid Hormones, and Vitamin D
- Bile Acids
- Steroid Hormones
- Vitamin D
- Lipid-Soluble Vitamins
- Vitamin A
- Vitamin E
- Vitamin K
- 16.8. Eicosanoids: Prostaglandins, Thromboxanes, and Leukotrienes
- 17.1. Interdependence of the Major Organs in Vertebrate Fuel Metabolism
- Fuel Inputs and Outputs
- Metabolic Division of Labor Among the Major Organs
- Brain
- Muscle
- Heart
- Adipose Tissue
- Liver
- Blood
- 17.2. Hormonal Regulation of Fuel Metabolism
- Actions of the Major Hormones
- Insulin
- Glucagon
- Epinephrine
- Coordination of Energy Homeostasis
- AMP-Activated Protein Kinase (AMPK)
- Mammalian Target of Rapamycin (mTOR)
- Sirtuins
- Endocrine Regulation of Energy Homeostasis
- 17.3. Responses to Metabolic Stress: Starvation, Diabetes
- Starvation
- Diabetes
- Foundation Figure: Energy Regulation
- 18.1. Utilization of Inorganic Nitrogen: The Nitrogen Cycle
- Biological Nitrogen Fixation
- Nitrate Utilization
- 18.2. Utilization of Ammonia: Biogenesis of Organic Nitrogen
- Glutamate Dehydrogenase: Reductive Amination of a-Ketoglutarate
- Glutamine Synthetase: Generation of Biologically Active Amide Nitrogen
- Carbamoyl Phosphate Synthetase: Generation of an Intermediate for Arginine and Pyrimidine Synthesis
- 18.3. The Nitrogen Economy and Protein Turnover
- Metabolic Consequences of the Absence of Nitrogen Storage Compounds
- Protein Turnover
- Intracellular Proteases and Sites of Turnover
- Chemical Signals for Turnover—Ubiquitination
- 18.4. Coenzymes Involved in Nitrogen Metabolism
- Pyridoxal Phosphate
- Folic Acid Coenzymes and One-Carbon Metabolism
- Discovery and Chemistry of Folic Acid
- Conversion of Folic Acid to Tetrahydrofolate
- Tetrahydrofolate in the Metabolism of One-Carbon Units
- Folic Acid in the Prevention of Heart Disease and Birth Defects
- B12 Coenzymes
- B12 Coenzymes and Pernicious Anemia
- 18.5. Amino Acid Degradation and Metabolism of Nitrogenous End Products
- Transamination Reactions
- Detoxification and Excretion of Ammonia
- Transport of Ammonia to the Liver
- The Krebs–Henseleit Urea Cycle
- 18.6. Pathways of Amino Acid Degradation
- Pyruvate Family of Glucogenic Amino Acids
- Oxaloacetate Family of Glucogenic Amino Acids
- a-Ketoglutarate Family of Glucogenic Amino Acids
- Succinyl-CoA Family of Glucogenic Amino Acids
- Acetoacetate/Acetyl-CoA Family of Ketogenic Amino Acids
- Phenylalanine and Tyrosine Degradation
- 18.7. Amino Acid Biosynthesis
- Biosynthetic Capacities of Organisms
- Amino Acid Biosynthetic Pathways
- Synthesis of Glutamate, Aspartate, Alanine, Glutamine, and Asparagine
- Synthesis of Serine and Glycine from 3-Phosphoglycerate
- Synthesis of Valine, Leucine, and Isoleucine from Pyruvate
- 18.8. Amino Acids as Biosynthetic Precursors
- S-Adenosylmethionine and Biological Methylation
- Precursor Functions of Glutamate
- Arginine Is the Precursor for Nitric Oxide and Creatine Phosphate
- Tryptophan and Tyrosine Are Precursors of Neurotransmitters and Biological Regulators
- 19.1. Outlines of Pathways in Nucleotide Metabolism
- Biosynthetic Routes: De Novo and Salvage Pathways
- Nucleic Acid Degradation and the Importance of Nucleotide Salvage
- PRPP, a Central Metabolite in De Novo and Salvage Pathways
- 19.2. De Novo Biosynthesis of Purine Ribonucleotides
- Synthesis of the Purine Ring
- Enzyme Organization in the Purine Biosynthetic Pathway
- Synthesis of ATP and GTP from Inosine Monophosphate
- 19.3 Purine Catabolism and Its Medical Significance
- Uric Acid, a Primary End Product
- Medical Abnormalities of Purine Catabolism
- Gout
- Lesch–Nyhan Syndrome
- Severe Combined Immunodeficiency Disease
- 19.4. Pyrimidine Ribonucleotide Metabolism
- De Novo Biosynthesis of UTP and CTP
- Glutamine-Dependent Amidotransferases
- Multifunctional Enzymes in Eukaryotic Pyrimidine Metabolism
- 19.5 Deoxyribonucleotide Metabolism
- Reduction of Ribonucleotides to Deoxyribonucleotides
- RNR Structure and Mechanism
- Source of Electrons for Ribonucleotide Reduction
- Regulation of Ribonucleotide Reductase Activity
- Regulation of dNTP Pools by Selective dNTP Degradation
- Biosynthesis of Thymine Deoxyribonucleotides
- Salvage Routes to Deoxyribonucleotides
- Thymidylate Synthase: A Target Enzyme for Chemotherapy
- 19.6. Virus-Directed Alterations of Nucleotide Metabolism
- 19.7. Other Medically Useful Analogs
- 20.1. An Overview of Hormone Action
- Chemical Nature of Hormones and Other Signaling Agents
- Hierarchical Nature of Hormonal Control
- Hormone Biosynthesis
- 20.2. Modular Nature of Signal Transduction Systems: G Protein-Coupled Signaling
- Receptors
- Receptors as Defined by Interactions with Drugs
- Receptors and Adenylate Cyclase as Distinct Components of Signal Transduction Systems
- Structural Analysis of G Protein-Coupled Receptors
- Transducers: G Proteins
- Actions of G Proteins
- Structure of G Proteins
- Consequences of Blocking GTPase
- The Versatility of G Proteins
- Interaction of GPCRs with G Proteins
- G Proteins in the Visual Process
- Effectors
- Second Messengers
- Cyclic AMP
- Cyclic GMP and Nitric Oxide
- Phosphoinositides
- 20.3. Receptor Tyrosine Kinases and Insulin Signaling
- 20.4. Hormones and Gene Expression: Nuclear Receptors
- 20.5. Signal Transduction, Growth Control, and Cancer
- Viral and Cellular Oncogenes
- Oncogenes in Human Tumors
- The Cancer Genome Mutational Landscape
- 20.6. Neurotransmission
- The Cholinergic Synapse
- Fast and Slow Synaptic Transmission
- Actions of Specific Neurotransmitters
- Drugs That Act in the Synaptic Cleft
- Peptide Neurotransmitters and Neurohormones
- Foundation Figure: Cell Signaling and Protein Regulation
- 21.1. Bacterial and Viral Genomes
- Viral Genomes
- Bacterial Genomes— The Nucleoid
- 21.2. Eukaryotic Genomes
- Genome Sizes
- Repetitive Sequences
- Satellite DNA
- Duplications of Functional Genes
- Alu Elements
- Introns
- Gene Families
- Multiple Variants of a Gene
- Pseudogenes
- The ENCODE Project and the Concept of “Junk DNA”
- 21.3. Physical Organization of Eukaryotic Genes: Chromosomes and Chromatin
- The Nucleus
- Chromatin
- Histones and Nonhistone Chromosomal Proteins
- The Nucleosome
- Higher-order Chromatin Structure in the Nucleus
- 21.4. Nucleotide Sequence Analysis of Genomes
- Restriction and Modification
- Properties of Restriction and Modification Enzymes
- Determining Genome Nucleotide Sequences
- Mapping Large Genomes
- Generating Physical Maps
- The Principle of Southern Analysis
- Southern Transfer and DNA Fingerprinting
- Locating Genes on the Human Genome
- Sequence Analysis Using Artificial Chromosomes
- Size of the Human Genome
- Tools of Biochemistry: 21A Polymerase Chain Reaction
- 22.1. Early Insights into DNA Replication
- 22.2. DNA Polymerases: Enzymes Catalyzing Polynucleotide Chain Elongation
- Structure and Activities of DNA Polymerase I
- DNA Substrates for the Polymerase Reaction
- Multiple Activities in a Single Polypeptide Chain
- Structure of DNA Polymerase I
- Discovery of Additional DNA Polymerases
- Structure and Mechanism of DNA Polymerases
- 22.3. Other Proteins at the Replication Fork
- Genetic Maps of E. coli and Bacteriophage T4
- Replication Proteins in Addition to DNA Polymerase
- Discontinuous DNA Synthesis
- RNA Primers
- Proteins at the Replication Fork
- The DNA Polymerase III Holoenzyme
- Sliding Clamp
- Clamp Loading Complex
- Single-Stranded DNA-Binding Proteins: Maintaining Optimal Template Conformation
- Helicases: Unwinding DNA Ahead of the Fork
- Topoisomerases: Relieving Torsional Stress
- Actions of Type I and Type II Topoisomerases
- The Four Topoisomerases of E. coli
- A Model of the Replisome
- 22.4. Eukaryotic DNA Replication
- DNA Polymerases
- Other Eukaryotic Replication Proteins
- Replication of Chromatin
- 22.5. Initiation of DNA Replication
- Initiation of E. coli DNA Replication at ori c
- Initiation of Eukaryotic Replication
- 22.6. Replication of Linear Genomes
- Linear Virus Genome Replication
- Telomerase
- 22.7. Fidelity of DNA Replication
- 3 Exonucleolytic Proofreading
- Polymerase Insertion Specificity
- DNA Precursor Metabolism and Genomic Stability
- Ribonucleotide Incorporation and Genomic Stability
- 22.8. RNA Viruses: The Replication of RNA Genomes
- RNA-Dependent RNA Replicases
- Replication of Retroviral Genomes
- 23.1. DNA Repair
- Types and Consequences of DNA Damage
- Direct Repair of Damaged DNA Bases: Photoreactivation and Alkyltransferases
- Photoreactivation
- O6-Alkylguanine Alkyltransferase
- Nucleotide Excision Repair: Excinucleases
- Base Excision Repair: DNA N-Glycosylases
- Replacement of Uracil in DNA by BER
- Repair of Oxidative Damage to DNA
- Mismatch Repair
- Double-Strand Break Repair
- Daughter-Strand Gap Repair
- Damage Response
- 23.2. Recombination
- Site-Specific Recombination
- Homologous Recombination
- Breaking and Joining of Chromosomes
- Models for Recombination
- Proteins Involved in Homologous Recombination
- 23.3. Gene Rearrangements
- Immunoglobulin Synthesis: Generating Antibody Diversity
- Transposable Genetic Elements
- Retroviruses
- Gene Amplification
- Tools of Biochemistry: 23A Manipulating the Genome
- Foundation Figure: Antibody Diversity and Use as Therapeutics
- 24.1. DNA as the Template for RNA Synthesis
- The Predicted Existence of Messenger RNA
- T2 Bacteriophage and the Demonstration of Messenger RNA
- RNA Dynamics in Uninfected Cells
- 24.2. Enzymology of RNA Synthesis: RNA Polymerase
- Biological Role of RNA Polymerase
- Structure of RNA Polymerase
- 24.3. Mechanism of Transcription in Bacteria
- Initiation of Transcription: Interactions with Promoters
- Initiation and Elongation: Incorporation of Ribonucleotides
- Punctuation of Transcription: Termination
- Factor-Independent Termination
- Factor-Dependent Termination
- 24.4. Transcription in Eukaryotic Cells
- RNA Polymerase I: Transcription of the Major Ribosomal RNA Genes
- RNA Polymerase III: Transcription of Small RNA Genes
- RNA Polymerase II: Transcription of Structural Genes
- Chromatin Structure and Transcription
- Transcriptional Elongation
- Termination of Transcription
- 24.5. Posttranscriptional Processing
- Bacterial mRNA Turnover
- Posttranscriptional Processing in the Synthesis of Bacterial rRNAs and tRNAs
- rRNA Processing
- tRNA Processing
- Processing of Eukaryotic mRNA
- Capping
- Splicing
- Alternative Splicing
- Tools of Biochemistry: 24A Analyzing the Transcriptome
- Tools of Biochemistry: 24B Chromatin Immunoprecipitation
- 25.1. An Overview of Translation
- 25.2. The Genetic Code
- How the Code Was Deciphered
- Features of the Code
- Deviations from the Genetic Code
- The Wobble Hypothesis
- tRNA Abundance and Codon Bias
- Punctuation: Stopping and Starting
- 25.3. The Major Participants in Translation: mRNA, tRNA, and Ribosomes
- Messenger RNA
- Transfer RNA
- Aminoacyl-tRNA Synthetases: The First Step in Protein Synthesis
- The Ribosome and Its Associated Factors
- Soluble Protein Factors in Translation
- Components of Ribosomes
- Ribosomal RNA Structure
- Internal Structure of the Ribosome
- 25.4. Mechanism of Translation
- Initiation
- Elongation
- Termination
- Suppression of Nonsense Mutations
- 25.5. Inhibition of Translation by Antibiotics
- 25.6. Translation in Eukaryotes
- 25.7. Rate of Translation; Polyribosomes
- 25.8. The Final Stages in Protein Synthesis: Folding and Covalent Modification
- Chain Folding
- Covalent Modification
- 25.9. Protein Targeting in Eukaryotes
- Proteins Synthesized in the Cytoplasm
- Proteins Synthesized on the Rough Endoplasmic Reticulum
- Role of the Golgi Complex
- 26.1. Regulation of Transcription in Bacteria
- The Lactose Operon—Earliest Insights into Transcriptional Regulation
- Isolation and Properties of the Lactose Repressor
- The Repressor Binding Site
- Regulation of the lac Operon by Glucose: A Positive Control System
- The CRP–DNA Complex
- Some Other Bacterial Transcriptional Regulatory Systems: Variations on a Theme
- Bacteriophage .: Multiple Operators, Dual Repressors, Interspersed Promoters and Operators
- The SOS Regulon: Activation of Multiple Operons by a Common Set of Environmental Signals
- Biosynthetic Operons: Ligand-Activated Repressors and Attenuation
- Applicability of the Operon Model—Variations on a Theme
- 26.2. Transcriptional Regulation in Eukaryotes
- Chromatin and Transcription
- Transcriptional Control Sites and Genes
- Nucleosome Remodeling Complexes
- Transcription Initiation
- Regulation of the Elongation Cycle by RNA Polymerase Phosphorylation
- 26.3. DNA Methylation, Gene Silencing, and Epigenetics
- DNA Methylation in Eukaryotes
- DNA Methylation and Gene Silencing
- Genomic Distribution of Methylated Cytosines
- Other Proposed Epigenetic Phenomena
- 5-Hydroxymethylcytosine
- Chromatin Histone Modifications
- 26.4. Regulation of Translation
- Regulation of Bacterial Translation
- Regulation of Eukaryotic Translation
- Phosphorylation of Eukaryotic Initiation Factors
- Long Noncoding RNAs
- 26.5. RNA Interference
- MicroRNAs
- Small Interfering RNAs
- 26.6. Riboswitches
- 26.7. RNA Editing
- Foundation Figure: Information Flow in Biological Systems
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