Lehninger Biochemistry: Core Concepts and Applications

Chapter 1: Biochemistry Concepts and Themes

1.1 Science and the Scientific Method

• What is Science?
• What is the Scientific Method?

1.2 Organisms, Cells, Chromosomes, and Genes

• Organisms Belong to Three Distinct Domains of Life
• Cells Are the Structural and Functional Units of All Living Organisms
• Viruses Cannot Live Independently of Cells
• Bacterial Cells Feature a Relatively Simple Architecture and Streamlined Lifestyles
• Eukaryotic Cells Have a Variety of Membranous Organelles
• Cells Contain a Wide Range of Supramolecular Structures
• Major Model Organisms and Systems are Useful in Biochemistry
• The Linear Sequence in DNA Encodes Proteins with Three-Dimensional Structures

1.3 The Organic Chemistry of Biochemistry

• Major Organic Species are Found in Cells
• Macromolecules Are the Major Constituents of Cells
• Molecular Weight and Molecular Mass are Expressed by Distinct Conventions
• Nucleophiles and Electrophiles Define How Many Reactions Proceed
• Cofactors Facilitate Particular Classes of Biochemical Reactions

1.4 A Review of Basic Thermodynamics

• Equilibrium Constants and Rate Constants Describe Distinct but Related Thermodynamic Parameters
• Organisms Transform Energy and Matter from Their Surroundings
• Creating and Maintaining Order Requires Work and Energy

1.5 Using Data Banks

Chapter 2: Water: The Chemistry of Life

2.1 Weak Interactions in Aqueous Systems

• Hydrogen Bonds Give Water Its Unusual Properties
• Water Interacts Electrostatically with Charged Solutes
• Nonpolar Gases Are Poorly Soluble in Water
• The Hydrophobic Effect is an Entropy-based Phenomenon
• van der Waals Interactions and Other Weak Interactions Are Key to Macromolecular Structure and Function

2.2 Ionization of Water, Weak Acids, and Weak Bases

• The Ionization of Water Is Expressed by an Equilibrium Constant
• The pH Scale Designates H+ and OH- Concentrations
• Weak Acids and Bases Have Characteristic Acid Dissociation Constants
• Titration Curves Reveal the pK_a of Weak Acids

2.3 Buffering against pH Changes in Biological Systems

• A Buffer System Resists Changes in pH in Response to Added Acid or Base.
• The Henderson-Hasselbalch Equation Relates pH, pK_a, and Buffer Concentration
• Weak Acids or Bases Buffer Cells and Tissues against pH Changes
• Phosphate and Bicarbonate Are Important Biological Buffer Systems Untreated Diabetes Produces Life-Threatening Acidosis

Chapter 3: Amino Acids, Peptides, and Proteins

3.1 Amino Acids

• What is an Amino Acid?
• The Amino Acid Residues in Proteins Are L Stereoisomers
• Amino Acids Can Be Classified by R Group
• Some Amino Acids Absorb Ultraviolet Light
• Uncommon Amino Acids Also Have Important Functions
• Amino Acids Can Act as Acids and Bases
• Amino Acids Differ in Their Acid-Base Properties

3.2 Peptides and Proteins

• Peptides Are Chains of Amino Acids
• Disulfide Bonds Occur in Some Proteins
• Ionization Behavior Can Distinguish Peptides
• Some Proteins Contain Chemical Groups Other Than Amino Acids

3.3 Purifying Proteins

• Proteins Can Be Separated and Purified
• Proteins Are Detected and Quantified Based on Their Functions
• Proteins Can Be Separated and Characterized by Electrophoresis

3.4 The Primary Structure of Proteins and Protein Chemistry

• There are Levels of Complexity to Protein Structure
• The Function of a Protein Depends on Its Amino Acid Sequence
• There are Multiple Ways to Reduce a Polypeptide Chain into Fragments.
• Mass Spectrometry Provides Information on Molecular Mass, Amino Acid Sequence, and Entire Proteomes
• Amino Acid Sequences Provide Important Biochemical and Evolutionary Information

Chapter 4: Protein Structure

4.1 Forces and Interactions that Stabilize Protein Structures

• Protein Structures Are Largely Stabilized by Weak Interactions
• Hydrogen Bonding, Ion Pairs, and van der Waals Interactions Also Contribute to Protein Folding
• The Conformation of the Peptide Bond Constrains Polypeptide Conformation

4.2 Secondary Protein Structure

• The ¿ Helix Maximizes the Use of Polypeptide Hydrogen Bonds
• The ß Strand is a Common Secondary Structure with an Extended Conformation
• Ramachandran Plots Describe the Distribution of Secondary Structure in a Protein

4.3 Tertiary and Quaternary Protein Structure

• Fibrous Proteins Have a Single Type of Secondary Structure
• The Fibrous Protein Collagen is the Most Abundant Protein in Mammals
• Silk is Made from a Fibrous Protein with b-sheet Secondary Structure
• Globular Proteins are Compact and Highly Varied in Three Dimensional Structure
• Protein Tertiary Structures can be Described in Terms of Motifs and Domains.
• Intrinsically Disordered Proteins Lack Stable Tertiary Structures.
• Quaternary Structure Describes the Organization of Multisubunit Proteins.
• Biomolecular Structures Can be Determined Using a Variety of Methods
• The Protein Data Bank is a Repository for Biomolecular Structures

4.4 Protein Denaturation and Folding

• Loss of Protein Structure Results in Loss of Function
• Amino Acid Sequence Determines Tertiary Structure
• Protein Folding Occurs by Defined Pathways and can be Assisted by Chaperones.
• Defects in Protein Folding Cause Human Disease

Chapter 5: Protein Function and Ligand Binding

5.1 Reversible Protein-Ligand Binding

• Ligands Bind to Proteins Reversibly at Binding Sites
• Protein-Ligand Interactions Can Be Described Quantitatively

5.2 Reversible Binding of a Protein to a Ligand: Oxygen-Binding by Myoglobin

• Oxygen Can Bind to a Heme Prosthetic Group
• Globins Are a Family of Oxygen-Binding Proteins
• The Binding of Oxygen to Myoglobin can be Described Quantitatively
• Protein Structure Affects How Ligands Bind

5.3 Reversible and Cooperative Binding of a Protein to a Ligand: Oxygen-Binding by Hemoglobin

• Hemoglobin Subunits Are Structurally Similar to Myoglobin
• Hemoglobin Undergoes a Structural Change on Binding Oxygen
• Hemoglobin Binds Oxygen Cooperatively
• Cooperative Ligand Binding Can Be Described Quantitatively
• Hemoglobin Also Transports H+ and CO2

5.4 Medical Conditions Related to Hemoglobin

• CO Binding to Hemoglobin Poses a Serious Health Risk
• Altered Hemoglobin Subunit Interactions in Sickle Cell Anemia Cause Pain and Suffering

Chapter 6: Protein Function and Enzymes

6.1 What are Enzymes?

• Most Enzymes Are Proteins
• Enzyme-catalyzed Reactions Occur Within Active Sites
• Enzymes Affect Reaction Rates, Not Equilibria
• Reaction Rates and Equilibria are Described by Constants

6.2 How Enzymes Work

• Noncovalent Interactions between Enzyme and Substrate Are Optimized in the Transition State
• Enzymes Use a Variety of Additional Chemical Mechanisms to Facilitate Catalysis
• Coenzymes Facilitate Particular Types of Reactions

6.3 Enzyme Kinetics

• The Steady State of an Enzyme-catalyzed Reaction Reflects the Concentration of ES
• The Relationship Between Substrate Concentration and Reaction Rate can be Described Quantitatively
• Scientists Compare Enzymes Using Vmax and Km.
• Enzymes are Subject to Reversible and Irreversible Inhibition

6.4 Chymotrypsin and Enzymatic Catalysis

• The Chymotrypsin Mechanism Involves Acylation and Deacylation of an Active Site Ser Residue
• An Understanding of Protease Mechanisms Led to Treatments for HIV
• An Understanding of Enzyme Mechanism Leads to Useful Antibiotics

6.5 Regulatory Enzymes

• Some Enzymes are Regulated by Allosteric Conformational Changes in Response to Modulator Binding
• Some Enzymes are Regulated by Reversible Covalent Modification
• Some Enzymes are Regulated by Proteolytic Cleavage of an Enzyme Precursor

Chapter 7: Carbohydrates

7.1 Monosaccharides and Disaccharides

• The Two Families of Monosaccharides Are Aldoses and Ketoses
• The Common Monosaccharides Have Cyclic Structures
• Sugars Containing and Forming Aldehydes are Reducing Sugars
• Disaccharides Consist of Two Monosaccharides Joined by a Glycosidic Bond

7.2 Polysaccharides

• Some Homopolysaccharides Are Storage Forms of Fuel While Others have Structural Roles
• Glycosaminoglycans Are Heteropolysaccharides of the Extracellular Matrix

7.3 Glycoconjugates: Peptidoglycans, Proteoglycans, Glycoproteins, and Glycolipids

• Peptidoglycan Reinforces the Bacterial Cell Wall
• Proteoglycans Are Glycosaminoglycan-Containing Macromolecules of the Cell Surface and Extracellular Matrix
• Glycoproteins Are Proteins with Covalently Attached Oligosaccharides
• Glycolipids and Lipopolysaccharides Are Membrane Components

7.4 Carbohydrates as Signaling Molecules

• Oligosaccharides Have Highly Diverse Structures
• Lectins Are Proteins That Bind Specifically to Complex Oligosaccharides and Mediate Many Biological Processes

Chapter 8: Lipids, Membranes, and Membrane Proteins

8.1 Membrane Lipids

• Fatty Acids are the Hydrocarbon Chain of Membrane Lipids
• Fatty Acid Composition of Lipids Impacts Health
• Structural Elements Determine Membrane Classes
• Membranes Lipids are Amphipathic Molecules that Form Lipid Bilayers
• Membrane Lipid Composition Impacts Membrane Fluidity

8.2 The Architecture of Membrane Proteins

• Membrane Proteins Differ in How They Associate with the Membrane Bilayer
• Integral Membrane Proteins Span Membranes and Can be Transporters
• Peripheral Membrane Proteins Interact with Membranes through Electrostatic Charge
• Lipid-anchored Proteins are Covalently Linked to Hydrophobic Anchors Embedded in the Membrane

8.3 Moving Molecules Through Membranes

• Membrane Transporters are Required to Move Large and Charged Molecules across Membranes
• Transport in and out of Cells May be Passive or Active
• Transporters and Ion Channels Share Structural Properties but Have Different Mechanisms
• The Glucose Transporter of Erythrocytes Mediates Passive Transport
• P-Type ATPases are Active Transporters that Change Conformation with Phosphoryl- Group Transfer from ATP
• Ion Channels Allow Rapid Movement of Ions Across Membranes

Chapter 9: Nucleotides and Nucleic Acids

9.1 Nucleotides

• Nucleotides Have Three Molecular Components
• The Common Nucleotides Have Many Uncommon Variants
• Phosphodiester Bonds Link Successive Nucleotides in Nucleic Acids
• The Properties of Nucleotide Bases Affect the Three-Dimensional Structure of Nucleic Acids

9.2 Nucleic Acid Structures

• DNA Is a Double Helix That Stores Genetic Information
• DNA Can Occur in Different Three-Dimensional Forms
• Certain DNA and RNA Sequences Adopt Unusual Structures
• Messenger RNAs Code for Polypeptide Chains
• Many RNAs Have More Complex Three-Dimensional Structures

9.3 Nucleic Acid Chemistry

• Double-Helical DNA and RNA Can Be Denatured
• Base Stacking Affects the UV Absorption Properties of DNA and RNA
• Nucleotides and Nucleic Acids Undergo Nonenzymatic Transformations

9.4 Nucleotide Roles in Cell Energetics and Signaling

• Nucleotides Carry Chemical Energy in Cells
• Some Nucleotides Are Regulatory Molecules or Signals
• Adenine Nucleotides Serve as Constituents of Many Enzymatic Cofactors; a Clue to the Origin of Life?

Chapter 10: Biological Information Part 1: DNA and RNA Metabolism

10.1 DNA Replication

• DNA Replication Follows a Set of Rules
• DNA Polymerases Synthesizes DNA
• DNA Replication Requires Many Enzymes and Protein Factors
• DNA Replication Occurs in Stages

10.2 DNA Repair and Organization

• All Cells Have Multiple DNA Repair Systems
• DNA Repair Can Also Occur in the Absence of Replication
• DNA Is Organized into Chromatin

10.3 Transcription and RNA Processing

• RNA Polymerases Synthesizes RNA
• RNA Replication Requires Many Enzymes and Protein Factors
• RNA Syntheses Occurs in Stages
• Medicines can Target or Be Made by RNA Polymerases
• Nearly All Eukaryotic RNAs Must Be Processed
• Reverse Transcriptases Produce DNA From RNA

10.4 Regulation of Transcription

• Transcription of Specific Genes Requires Regulatory Proteins in Addition to RNA Polymerase
• Regulation of Gene Expression in Bacteria
• Regulation of Gene Expression in Eukaryotes

Chapter 11: Biological Information Part 2: Protein Metabolism

11.1 The Genetic Code

• The Genetic Code Describes How Sets of Nucleic Acids Correspond to Particular Amino Acids
• tRNA Anticodons Base Pair with Codons
• tRNAs are Charged with Amino Acids for Protein Synthesis
• tRNA Charging Requires ATP Hydrolysis

11.2 Structure and Function of Ribosomes

• Ribosomes Catalyze Protein Synthesis
• Protein Synthesis Occurs in Stages
• Translation Factors Interact with the Ribosome During Elongation and Termination
• Protein Synthesis by the Ribosomes is Energetically Expensive

11.3 Protein Folding, Modification, and Degradation

• Chaperones Help Proteins Fold into Their Native Conformation
• Posttranslational Modifications are Critical for the Function of Many Proteins
• Protein Degradation is Highly Regulated in Eukaryotes by the Ubiquitin/Proteosome Pathway

11.4 Translational Control

• Riboswitches, Small RNAs, and Attenuation Can Control Gene Expression in Bacteria
• Eukaryotes Use mRNA Binding Proteins, RNAi, and MicroRNAs to Regulate Protein Production

Chapter 12: Nucleic Acid Technologies

12.1 Defining Genomic Information

• The Genome is All of the Nucleic Acid Needed to Support the Life of an Organism
• The Polymerase Chain Reaction Provides Targeted Amplification of Genomic Information
• DNA Can Be Sequenced
• Sanger Sequencing has been Automated
• Next-Generation DNA Sequencing Produces Complete Genome Sequences
• RNA Can be Sequenced by First Copying the RNA to DNA with Reverse Transcriptase

12.2 Altering Genomic Information

• Joining DNA Segments from Different Sources Yields Recombinant DNA Segments Can be Joined Without Using Restriction Enzymes
• Cloned DNA Can be Altered to Study Genes and Proteins
• CRISPR/Cas Systems Allows Targeted Cleavage or Modification of Genomic Information

12.3 Using Genomic Information

• An Altered Genome can Lead to an Altered Transcriptome and Proteome
• Genomic Information Can be Used to Identify the Source of Genetic Diseases
• Genomic Information Can be Used to Investigate Crimes

Chapter 13: Introduction to Intermediary Metabolism

13.1 What is Metabolism?

• Molecules are Metabolized by Anabolic and Catabolic Pathways
• Metabolic Pathways can be Converging, Diverging, or Cyclic

13.2 Common Enzyme Reactions in Metabolism

• Carbonyls are Important for Making and Breaking Carbon-Carbon Bonds
• Rearrangement and Isomerization Reactions Reposition Reactive Groups
• Elimination Reactions Release Good Leaving Groups
• Free-Radical Reactions Involve Complex Rearrangements
• Group Transfer Reactions Add or Subtract Functional Groups to Metabolites
• Oxidation-Reduction Reactions Involve Electron Transfer to or from Biomolecules

13.3 ATP and Phosphoryl Group Transfers

• ATP Contains High Energy Phosphodiester Bonds
• ATP Hydrolysis is Thermodynamically Very Favorable
• Many Other Metabolites and Enzyme Reaction Intermediates Also Have Large, Negative Free Energies of Hydrolysis
• ATP Donates Phosphoryl, Pyrophosphoryl, and Adenyl Groups
• ATP can Provide Energy by Group Transfers, Not Just by Hydrolysis

13.4 Biological Oxidation-Reduction Reactions

• Oxidation-Reduction Reactions Can Be Described as Half-Reactions
• Biological Oxidations Often Involve Dehydrogenation
• A Few Types of Coenzymes and Proteins Serve as Universal Electron Carriers

13.5 Regulation of Metabolic Pathways

• Cells and Organisms Maintain a Dynamic Steady State
• Both the Amount and the Catalytic Activity of an Enzyme Can Be Regulated

Chapter 14: Carbohydrate Metabolism Part 1: Glycolysis and Glycogen Synthesis

14.1 An Overview of Glycolysis

• Glycolysis Has Two Phases: The Preparatory and Payoff Phases
• In Glycolysis the Potential Energy of Glucose is Partially Converted to ATP and NADH
• Phosphorylated Intermediates are Important in Glycolysis

14.2 The Preparatory and Payoff Phases of Glycolysis

• The Preparatory Phase of Glycolysis Converts Glucose to a 3-carbon Metabolite and Consumes ATP
• The Payoff Phase of Glycolysis Yields ATP, NADH, and Pyruvate
• The Glycolytic Pathway Conserves Part of the Energy Released as ATP and NADH:
• Feeder Pathways Provide Additional Fuel for Glycolysis

14.3 Anaerobic Fermentation of Pyruvate

• There Are Two Anaerobic Fermentation Pathways
• The Warburg Effect Describes How Cancer Cells Rely Almost Entirely on Glycolysis for Energy

14.4 The Pentose Phosphate Pathway

• The Pentose Phosphate Pathway Generates NADPH and Essential Pentose Phosphates
• The Oxidative Phase Produces NADPH and Pentose Phosphates
• The Nonoxidative Phase Recycles Pentose Phosphates to Glucose 6-Phosphate, Fructose 6-Phosphate, and Glyceraldehyde 3-Phosphate
• NADPH Produced by the Pentose Phosphate Pathway Defends Cells from Reactive Oxygen Species
• Deficiencies in the Oxidative Phase of the Pentose Phosphate Pathway Have Serious Health Consequences

14.5 Glycogen Synthesis

• Glycogen Provides a Specialized Molecular Structure for Glucose Storage
• The Sugar Nucleotide UDP-Glucose Donates Glucose for Glycogen Synthesis
• Defects in Glycogen Synthesis have Important Medical Consequences

Chapter 15: Carbohydrate Metabolism Part 2: Gluconeogenesis and Glycogen Degradation

15.1 Gluconeogenesis

• Gluconeogenesis and Glycolysis Share Many But Not All Steps and Enzymes
• Glycolysis Enzymes are Bypassed at Three Steps in Gluconeogenesis
• Gluconeogenesis is Energetically Expensive and Essential

15.2 Coordinated Regulation of Glycolysis and Gluconeogenesis

• Hexokinase Isozymes Are Affected Differently by Their Product, Glucose 6-Phosphate
• Phosphofructokinase-1 and Fructose 1,6-Bisphosphatase Are Reciprocally Regulated
• Fructose 2,6-Bisphosphate Is a Potent Allosteric Regulator of PFK-1 and FBPase-1

15.3 Breakdown of Glycogen and Its Regulation

• Glycogen Breakdown Is Catalyzed by Glycogen Phosphorylase
• Glycogen Phosphorylase Is Regulated by Hormone-Stimulated Phosphorylation and by Allosteric Effectors
• Allosteric and Hormonal Signals Coordinate Carbohydrate Metabolism Throughout the Body

Chapter 16: Pyruvate Oxidation and the Citric Acid Cycle

16.1 Conversion of Pyruvate to Acetyl-CoA

• The Citric Acid Cycle Occurs in Mitochondria
• Pyruvate Is Oxidized by Pyruvate Dehydrogenase to Generate Acetyl-CoA, NADH, and CO2
• The Pyruvate Dehydrogenase Complex Promotes a Multi-stage Reaction Sequence
• Pyruvate Dehydrogenase is Subject to Regulation

16.2 The Citric Acid Cycle

• Citrate, the First Tricarboxylic Acid, Forms in Step 1
• A Citrate Hydroxyl Group Moves in Step 2
• Following the Formation of Isocitrate, Two Oxidative Decarboxylations that Form CO2 Occur with Different Mechanisms
• Succinyl-CoA Synthetase Promotes the Formation of Succinate and GTP in Step 5
• The Final Three Steps Convert Succinate to Oxaloacetate Via a Common Oxidative Path
• The Energy of Oxidation is Conserved in the Citric Acid Cycle
• The Concentration of Key Metabolites Regulates Flux Through the Citric Acid Cycle

16.3 The Citric Acid Cycle as a Metabolic Hub

• The Citric Acid Cycle Plays a Central Role in Catabolism and Anabolism
• A Variety of Reactions Replenish Citric Acid Cycle Intermediates or Supplement Cycle Products

16.4 The Citric Acid Cycle Affects Cell State and Disease State

• Changes in Cell State Can be Accompanied by Flux Through a Non-canonical Citric Acid Cycle
• Vitamin Deficiencies Result in Disease
• Amino Acid Substitutions in Isocitrate Dehydrogenase Facilitate Tumor Growth

Chapter 17: Lipid Catabolism and Anabolism

17.1 The Fed State: Digestion, Synthesis, and Storage of Fats

• Biosynthesis of Fatty Acids Requires Two Enzyme Complexes
• Fatty Acid Synthesis Is Tightly Regulated
• Free Fatty Acids Are Incorporated Into Glycerolipids
• Triacylglycerol Biosynthesis Is Regulated by Hormones

17.2 Synthesis and Transport of Cholesterol

• Cholesterol Is Made from Acetyl-CoA in Four Stages
• Cholesterol Has Several Fates
• Cholesterol and Other Lipids Are Carried as Lipoprotein Particles
• HDL and LDL Cholesterol Enter Cells through Receptor-Mediated Interactions
• Dysregulation of Cholesterol Can Lead to Cardiovascular Disease

17.3 The Fasted State: Fatty Acid Oxidation and Production of Ketone Bodies

• Lipid Catabolism Occurs In Fasted States
• Fatty Acid Oxidation Occurs In The Mitochondria
• Regulation of Fatty Acid Oxidation By Compartmentalization
• Ketone Body are Formed in the Liver and Exported to Other Tissues
• Ketone Bodies Are Overproduced in Diabetes and Starvation

Chapter 18: Amino Acid Catabolism and Anabolism

18.1 The Worldwide Nitrogen Web and its Many Interfaces With Living Systems

• The Global Nitrogen Web Makes Atmospheric Nitrogen Available to Cells
• Nitrogen is Converted to Ammonia by Enzymes of the Nitrogenase Complex
• Ammonia Is Incorporated into Biomolecules through Glutamate and Glutamine
• Amino Groups are Distributed Primarily via Transamination Facilitated by Pyridoxal Phosphate
• Ammonia Generated by Some Cellular Processes is Toxic to Animals
• A Few Amino Acids Play Special Roles in Nitrogen Metabolism

18.2 Disposal of Amino Groups via the Urea Cycle

• In Extrahepatic Tissues, Amino Groups are Incorporated into Glutamine for Transport to the Liver
• The Urea Cycle Disposes of Excess Amino Groups
• Connections Among Metabolic Pathways Reduce the Energetic Cost of Urea Synthesis

18.3 Amino Acid Catabolism and Anabolism

• Amino Acid Catabolism Produces Pyruvate, Acetyl-CoA, and Citric Acid Cycle intermediates
• Several Enzyme Cofactors Play Important Roles in Amino Acid Catabolism
• Some Genetic Deficiency Diseases are Linked to Amino Acid Catabolism
• Amino Acid Anabolism is often Not the Reverse of Amino Acid Catabolism
• Organisms Vary Greatly in Their Ability to Synthesize the 20 Common Amino Acids
• Ketoglutarate Gives Rise to Glutamate, Glutamine, Proline, and Arginine

18.4 Molecules Derived from Amino Acids

• Heme is Derived from Glycine and Succinyl-CoA
• Biological Amines Are Products of Amino Acid Decarboxylation
• Glutathione is Synthesized from Glutamate, Cysteine, and Glycine

18.5 Nucleotide Biosynthesis

• The Ribose in Nucleotides is Derived from Phosphoribosyl Pyrophosphate
• Pyrimidine Nucleotides Are Made from Aspartate, PRPP, and Carbamoyl Phosphate
• De Novo Purine Nucleotide Synthesis Begins with PRPP
• Ribonucleotides Are the Precursors of Deoxyribonucleotides
• Thymidylate Is Derived from dCDP and dUMP

Chapter 19: Electron Transfer and Oxidative Phosphorylation

19.1 The Mitochondrial Electron Transport Chain

• Chemiosmotic Theory Describes How Electron Flow Couples to ATP Synthesis in Mitochondria
• Mitochondrial Architecture Facilitates Electron Transport and ATP Synthesis
• Dehydrogenases Funnel Electrons to Universal Electron Acceptors
• Electrons Pass through a Series of Membrane-Bound Carriers
• Electron Carriers Function in Multienzyme Complexes
• The Energy of Electron Transfer is Conserved in a Proton Gradient
• Reactive Oxygen Species are Generated during Oxidative Phosphorylation

19.2 ATP Synthesis

• In the Chemiosmotic Model, Oxidation and Phosphorylation Are Obligately Coupled
• ATP Synthase Has Two Functional Domains
• Chemiosmotic Coupling Allows Nonintegral Stoichiometries of Consumption and ATP Synthesis
• Shuttle Systems Indirectly Convey Cytosolic NADH into Mitochondria for Oxidation
• Uncoupling the Proton Gradient from ATP Synthesis Produces Heat

19.3 Regulation of Oxidative Phosphorylation and Mitochondrial Disease

• An Inhibitory Protein Prevents ATP Hydrolysis during Hypoxia
• Hypoxia Leads to ROS Production and Several Adaptive Responses
• ATP Producing Pathways Are Regulated
• Mitochondrial Enzyme Defects Cause Disease

Chapter 20: Metabolism and Biosignaling

20.1 Hormone Structure and Action

• Hormones Act Through Specific High-Affinity Cellular Receptors
• Hormones are Chemically Diverse
• Hormones Regulate Glucose Levels
• Diabetes Mellitus Arises from Defects in Insulin Production or Action

20.2 Tissue Specific Metabolism

• The Liver Processes and Distributes Nutrients in Feeding
• The Liver Produces Ketone Bodies to Fuel Perip