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Lehninger principles of biochemistry / David L. Nelson, Michael M. Cox.
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Title:Lehninger principles of biochemistry / David L. Nelson, Michael M. Cox.
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Variant Title:Principles of biochemistry.
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Author/Creator:Nelson, David L. (David Lee), 1942- author.
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Other Contributors/Collections:Cox, Michael M., author.
Lehninger, Albert L. Principles of biochemistry.
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Published/Created:New York : W.H. Freeman, [2017].
c2017.
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Holdings
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Location:OKANAGAN LIBRARY stacksWhere is this?
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Call Number: QU4 .N425l 2017
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Number of Items:1
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Status:Available
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Location:
c.1
Temporarily shelved at WOODWARD LIBRARY reserve collectionWhere is this?
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Call Number: QU4 .N425l 2017
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Number of Items:1
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Status:Available
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Location:OKANAGAN LIBRARY stacksWhere is this?
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Library of Congress Subjects:Biochemistry.
Biochemistry--Problems, exercises, etc.
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Medical Subjects: Biochemistry.
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Genre/Form:Problems and exercises.
Textbooks.
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Edition:7th edition
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Description:xxxiv, 1, 172, AS-34, G-20, I-45 pages : illustrations (chiefly color), color maps ; 29 cm
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Summary:"Lehninger Principles of Biochemistry ... brings clarity and coherence to an often unwieldy discipline, offering a thoroughly updated survey of biochemistry's enduring principles, definitive discoveries, and groundbreaking new advances with each edition.This new Seventh Edition maintains the qualities that have distinguished the text since Albert Lehninger's original edition--clear writing, careful explanations of difficult concepts, helpful problem-solving support, and insightful communication of contemporary biochemistry's core ideas, new techniques, and pivotal discoveries. Again, David Nelson and Michael Cox introduce students to an extraordinary amount of exciting new findings without an overwhelming amount of extra discussion or detail." -- Publisher description.
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Notes:Supplementary material available via the World Wide Web.
Includes bibliographic references and index.
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ISBN:9781464126116
1464126119
1464187975
9781464187971
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Contents:Machine generated contents note: 1. Foundations of Biochemistry
1.1. Cellular Foundations
Cells Are the Structural and Functional Units of All Living Organisms
Cellular Dimensions Are Limited by Diffusion
Organisms Belong to Three Distinct Domains of Life
Organisms Differ Widely in Their Sources of Energy and Biosynthetic Precursors
Bacterial and Archaeal Cells Share Common Features but Differ in Important Ways
Eukaryotic Cells Have a Variety of Membranous Organelles, Which Can Be Isolated for Study
Cytoplasm Is Organized by the Cytoskeleton and Is Highly Dynamic
Cells Build Supramolecular Structures
In Vitro Studies May Overlook Important Interactions among Molecules
1.2. Chemical Foundations
Biomolecules Are Compounds of Carbon with a Variety of Functional Groups
BOX 1-1 Molecular Weight, Molecular Mass, and Their Correct Units
Cells Contain a Universal Set of Small Molecules
Macromolecules Are the Major Constituents of Cells
Three-Dimensional Structure Is Described by Configuration and Conformation
Box 1-2 Louis Pasteur and Optical Activity: In Vino, Veritas
Interactions between Biomolecules Are Stereospecific
1.3. Physical Foundations
Living Organisms Exist in a Dynamic Steady State, Never at Equilibrium with Their Surroundings
Organisms Transform Energy and Matter from Their Surroundings
Box 1-3 Entropy: Things Fall Apart
Flow of Electrons Provides Energy for Organisms
Creating and Maintaining Order Requires Work and Energy
Energy Coupling Links Reactions in Biology
Keq and ΔG° Are Measures of a Reaction's Tendency to Proceed Spontaneously
Enzymes Promote Sequences of Chemical Reactions
Metabolism Is Regulated to Achieve Balance and Economy
1.4. Genetic Foundations
Genetic Continuity Is Vested in Single DNA Molecules
Structure of DNA Allows Its Replication and Repair with Near-Perfect Fidelity
Linear Sequence in DNA Encodes Proteins with Three-Dimensional Structures
1.5. Evolutionary Foundations
Changes in the Hereditary Instructions Allow Evolution
Biomolecules First Arose by Chemical Evolution
RNA or Related Precursors May Have Been the First Genes and Catalysts
Biological Evolution Began More Than Three and a Half Billion Years Ago
First Cell Probably Used Inorganic Fuels
Eukaryotic Cells Evolved from Simpler Precursors in Several Stages
Molecular Anatomy Reveals Evolutionary Relationships
Functional Genomics Shows the Allocations of Genes to Specific Cellular Processes
Genomic Comparisons Have Increasing Importance in Human Biology and Medicine
I. STRUCTURE AND CATALYSIS
2. Water
2.1. Weak Interactions in Aqueous Systems
Hydrogen Bonding Gives Water Its Unusual Properties
Water Forms Hydrogen Bonds with Polar Solutes
Water Interacts Electrostatically with Charged Solutes
Entropy Increases as Crystalline Substances Dissolve
Nonpolar Gases Are Poorly Soluble in Water
Nonpolar Compounds Force Energetically Unfavorable Changes in the Structure of Water
van der Waals Interactions Are Weak Interatomic Attractions
Weak Interactions Are Crucial to Macromolecular Structure and Function
Solutes Affect the Colligative Properties of Aqueous Solutions
2.2. Ionization of Water, Weak Acids, and Weak Bases
Pure Water Is Slightly Ionized
Ionization of Water Is Expressed by an Equilibrium Constant
pH Scale Designates the H+ and OH~ Concentrations
Weak Acids and Bases Have Characteristic Acid Dissociation Constants
Titration Curves Reveal the pKa of Weak Acids
2.3. Buffering against pH Changes in Biological Systems
Buffers Are Mixtures of Weak Acids and Their Conjugate Bases
Henderson-Hasselbalch Equation Relates pH, pka, and Buffer Concentration
Weak Acids or Bases Buffer Cells and Tissues against pH Changes
Untreated Diabetes Produces Life-Threatening Acidosis
BOX 2-1 MEDICINE On Being One's Own Rabbit (Don't Try This at Home!)
2.4. Water as a Reactant
2.5. Fitness of the Aqueous Environment for Living Organisms
3. Amino Acids, Peptides, and Proteins
3.1. Amino Acids
Amino Acids Share Common Structural Features
Amino Acid Residues in Proteins Are L Stereoisomers
Amino Acids Can Be Classified by R Group
BOX 3-1 METHODS Absorption of Light by Molecules: The Lambert-Beer Law
Uncommon Amino Acids Also Have Important Functions
Amino Acids Can Act as Acids and Bases
Amino Acids Have Characteristic Titration Curves
Titration Curves Predict the Electric Charge of Amino Acids
Amino Acids Differ in Their Acid-Base Properties
3.2. Peptides and Proteins
Peptides Are Chains of Amino Acids
Peptides Can Be Distinguished by Their Ionization Behavior
Biologically Active Peptides and Polypeptides Occur in a Vast Range of Sizes and Compositions
Some Proteins Contain Chemical Groups Other Than Amino Acids
3.3. Working with Proteins
Proteins Can Be Separated and Purified
Proteins Can Be Separated and Characterized by Electrophoresis
Unseparated Proteins Can Be Quantified
3.4. Structure of Proteins: Primary Structure
Function of a Protein Depends on Its Amino Acid Sequence
Amino Acid Sequences of Millions of Proteins Have Been Determined
Protein Chemistry Is Enriched by Methods Derived from Classical Polypeptide Sequencing
Mass Spectrometry Offers an Alternative Method to Determine Amino Acid Sequences
Small Peptides and Proteins Can Be Chemically Synthesized
Amino Acid Sequences Provide Important Biochemical Information
Protein Sequences Help Elucidate the History of Life on Earth
BOX 3-2 Consensus Sequences and Sequence Logos
4. Three-Dimensional Structure of Proteins
4.1. Overview of Protein Structure
Protein's Conformation Is Stabilized Largely by Weak Interactions
Peptide Bond Is Rigid and Planar
4.2. Protein Secondary Structure
α Helix Is a Common Protein Secondary Structure
BOX 4-1 METHODS Knowing the Right Hand from the Left
Amino Acid Sequence Affects Stability of the a Helix
β Conformation Organizes Polypeptide Chains into Sheets
β Turns Are Common in Proteins
Common Secondary Structures Have Characteristic Dihedral Angles
Common Secondary Structures Can Be Assessed by Circular Dichroism
4.3. Protein Tertiary and Quaternary Structures
Fibrous Proteins Are Adapted for a Structural Function
BOX 4-2 Permanent Waving Is Biochemical Engineering
BOX 4-3 MEDICINE Why Sailors, Explorers, and College Students Should Eat Their Fresh Fruits and Vegetables
Structural Diversity Reflects Functional Diversity in Globular Proteins
Myoglobin Provided Early Clues about the Complexity of Globular Protein Structure
BOX 4-4 Protein Data Bank
Globular Proteins Have a Variety of Tertiary Structures
BOX 4-5 METHODS Methods for Determining the Three-Dimensional Structure of a Protein
Some Proteins or Protein Segments Are Intrinsically Disordered
Protein Motifs Are the Basis for Protein Structural Classification
Protein Quaternary Structures Range from Simple Dimers to Large Complexes
4.4. Protein Denaturation and Folding
Loss of Protein Structure Results in Loss of Function
Amino Acid Sequence Determines Tertiary Structure
Polypeptides Fold Rapidly by a Stepwise Process
Some Proteins Undergo Assisted Folding
Defects in Protein Folding Provide the Molecular Basis for a Wide Range of Human Genetic Disorders
BOX 4-6 MEDICINE Death by Misfolding: The Prion Diseases
5. Protein Function
5.1. Reversible Binding of a Protein to a Ligand: Oxygen-Binding Proteins
Oxygen Can Bind to a Heme Prosthetic Group
Globins Are a Family of Oxygen-Binding Proteins
Myoglobin Has a Single Binding Site for Oxygen
Protein-Ligand Interactions Can Be Described Quantitatively
Protein Structure Affects How Ligands Bind
Hemoglobin Transports Oxygen in Blood
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
Two Models Suggest Mechanisms for Cooperative Binding
BOX 5-1 MEDICINE Carbon Monoxide: A Stealthy Killer
Hemoglobin Also Transports H+ and CO2
Oxygen Binding to Hemoglobin Is Regulated by 2,3-Bisphosphoglycerate
Sickle Cell Anemia Is a Molecular Disease of Hemoglobin
5.2. Complementary Interactions between Proteins and Ligands: The Immune System and Immunoglobulins
Immune Response Includes a Specialized Array of Cells and Proteins
Antibodies Have Two Identical Antigen-Binding Sites
Antibodies Bind Tightly and Specifically to Antigen
Antibody-Antigen Interaction Is the Basis for a Variety of Important Analytical Procedures
5.3. Protein Interactions Modulated by Chemical Energy: Actin, Myosin, and Molecular Motors
Major Proteins of Muscle Are Myosin and Actin
Additional Proteins Organize the Thin and Thick Filaments into Ordered Structures
Myosin Thick Filaments Slide along Actin Thin Filaments
6. Enzymes
6.1. Introduction to Enzymes
Most Enzymes Are Proteins
Enzymes Are Classified by the Reactions They Catalyze
6.2. How Enzymes Work
Enzymes Affect Reaction Rates, Not Equilibria
Reaction Rates and Equilibria Have Precise Thermodynamic Definitions
Few Principles Explain the Catalytic Power and Specificity of Enzymes
Weak Interactions between Enzyme and Substrate Are Optimized in the Transition State
Contents note continued: Binding Energy Contributes to Reaction Specificity and Catalysis
Specific Catalytic Groups Contribute to Catalysis
6.3. Enzyme Kinetics as an Approach to Understanding Mechanism
Substrate Concentration Affects the Rate of Enzyme-Catalyzed Reactions
Relationship between Substrate Concentration and Reaction Rate Can Be Expressed Quantitatively
Kinetic Parameters Are Used to Compare Enzyme Activities
BOX 6-1 Transformations of the Michael is-Men ten Equation: The Double-Reciprocal Plot
Many Enzymes Catalyze Reactions with Two or More Substrates
Enzyme Activity Depends on pH
Pre-Steady State Kinetics Can Provide Evidence for Specific Reaction Steps
Enzymes Are Subject to Reversible or Irreversible Inhibition
BOX 6-2 Kinetic Tests for Determining Inhibition Mechanisms
BOX 6-3 MEDICINE Curing African Sleeping Sickness with a Biochemical Trojan Horse
6.4. Examples of Enzymatic Reactions
Chymotrypsin Mechanism Involves Acylation and Deacylation of a Ser Residue
Understanding of Protease Mechanisms Leads to New Treatments for HIV Infections
Hexokinase Undergoes Induced Fit on Substrate Binding
Enolase Reaction Mechanism Requires Metal Ions
Lysozyme Uses Two Successive Nucleophilic Displacement Reactions
Understanding of Enzyme Mechanism Produces Useful Antibiotics
6.5. Regulatory Enzymes
Allosteric Enzymes Undergo Conformational Changes in Response to Modulator Binding
Kinetic Properties of Allosteric Enzymes Diverge from Michaelis-Menten Behavior
Some Enzymes Are Regulated by Reversible Covalent Modification
Phosphoryl Groups Affect the Structure and Catalytic Activity of Enzymes
Multiple Phosphorylations Allow Exquisite Regulatory Control
Some Enzymes and Other Proteins Are Regulated by Proteolytic Cleavage of an Enzyme Precursor
Cascade of Proteolytically Activated Zymogens Leads to Blood Coagulation
Some Regulatory Enzymes Use Several Regulatory Mechanisms
7. Carbohydrates and Glycobiology
7.1. Monosaccharides and Disaccharides
Two Families of Monosaccharides Are Aldoses and Ketoses
Monosaccharides Have Asymmetric Centers
Common Monosaccharides Have Cyclic Structures
Organisms Contain a Variety of Hexose Derivatives
BOX 7-1 MEDICINE Blood Glucose Measurements in the Diagnosis and Treatment of Diabetes
Monosaccharides Are Reducing Agents
Disaccharides Contain a Glycosidic Bond
BOX 7-2 Sugar Is Sweet, and So Are... a Few Other Things
7.2. Polysaccharides
Some Homopolysaccharides Are Storage Forms of Fuel
Some Homopolysaccharides Serve Structural Roles
Steric Factors and Hydrogen Bonding Influence Homopolysaccharide Folding
Bacterial and Algal Cell Walls Contain Structural Heteropolysaccharides
Glycosaminoglycans Are Heteropolysaccharides of the Extracellular Matrix
7.3. Glycoconjugates: Proteoglycans, Glycoproteins, and Glycosphingolipids
Proteoglycans Are Glycosaminoglycan-Containing Macromolecules of the Cell Surface and Extracellular Matrix
MEDICINE Defects in the Synthesis or Degradation of Sulfated Glycosaminoglycans Can Lead to Serious Human Disease
Glycoproteins Have Covalently Attached Oligosaccharides
Glycolipids and Lipopolysaccharides Are Membrane Components
7.4. Carbohydrates as Informational Molecules: The Sugar Code
Lectins Are Proteins That Read the Sugar Code and Mediate Many Biological Processes
Lectin-Carbohydrate Interactions Are Highly Specific and Often Multivalent
7.5. Working with Carbohydrates
8. Nucleotides and Nucleic Acids
8.1. Some Basics
Nucleotides and Nucleic Acids Have Characteristic Bases and Pentoses
Phosphodiester Bonds Link Successive Nucleotides in Nucleic Acids
Properties of Nucleotide Bases Affect the Three-Dimensional Structure of Nucleic Acids
8.2. Nucleic Acid Structure
DNA Is a Double Helix That Stores Genetic Information
DNA Can Occur in Different Three-Dimensional Forms
Certain DNA Sequences Adopt Unusual Structures
Messenger RNAs Code for Polypeptide Chains
Many RNAs Have More Complex Three-Dimensional Structures
8.3. Nucleic Acid Chemistry
Double-Helical DNA and RNA Can Be Denatured
Nucleotides and Nucleic Acids Undergo Nonenzymatic Transformations
Some Bases of DNA Are Methylated
Chemical Synthesis of DNA Has Been Automated
Gene Sequences Can Be Amplified with the Polymerase Chain Reaction
Sequences of Long DNA Strands Can Be Determined
BOX 8-1 Potent Weapon in Forensic Medicine
DNA Sequencing Technologies Are Advancing Rapidly
8.4. Other Functions of Nucleotides
Nucleotides Carry Chemical Energy in Cells
Adenine Nucleotides Are Components of Many Enzyme Cofactors
Some Nucleotides Are Regulatory Molecules
Adenine Nucleotides Also Serve as Signals
9. DNA-Based Information Technologies
9.1. Studying Genes and Their Products
Genes Can Be Isolated by DNA Cloning
Restriction Endonucleases and DNA Ligases Yield Recombinant DNA
Cloning Vectors Allow Amplification of Inserted DNA Segments
Cloned Genes Can Be Expressed to Amplify Protein Production
Many Different Systems Are Used to Express Recombinant Proteins
Alteration of Cloned Genes Produces Altered Proteins
Terminal Tags Provide Handles for Affinity Purification
Polymerase Chain Reaction Can Be Adapted for Convenient Cloning
9.2. Using DNA-Based Methods to Understand Protein Function
DNA Libraries Are Specialized Catalogs of Genetic Information
Sequence or Structural Relationships Provide Information on Protein Function
Fusion Proteins and Immunofluorescence Can Reveal the Location of Proteins in Cells
Protein-Protein Interactions Can Help Elucidate Protein Function
DNA Microarrays Reveal RNA Expression Patterns and Other Information
Inactivating or Altering a Gene with CRISPR Can Reveal Gene Function
9.3. Genomics and the Human Story
BOX 9-1 MEDICINE Personalized Genomic Medicine
Annotation Provides a Description of the Genome
Human Genome Contains Many Types of Sequences
Genome Sequencing Informs Us about Our Humanity
Genome Comparisons Help Locate Genes Involved in Disease
Genome Sequences Inform Us about Our Past and Provide Opportunities for the Future
BOX 9-2 Getting to Know Humanity's Next of Kin
10. Lipids
10.1. Storage Lipids
Fatty Acids Are Hydrocarbon Derivatives
Triacylglycerols Are Fatty Acid Esters of Glycerol
Triacylglycerols Provide Stored Energy and Insulation
Partial Hydrogenation of Cooking Oils Improves Their Stability but Creates Fatty Acids with Harmful Health Effects
Waxes Serve as Energy Stores and Water Repellents
10.2. Structural Lipids in Membranes
Glycerophospholipids Are Derivatives of Phosphatidic Acid
Some Glycerophospholipids Have Ether-Linked Fatty Acids
Chloroplasts Contain Galactolipids and Sulfolipids
Archaea Contain Unique Membrane Lipids
Sphingolipids Are Derivatives of Sphingosine
Sphingolipids at Cell Surfaces Are Sites of Biological Recognition
Phospholipids and Sphingolipids Are Degraded in Lysosomes
Sterols Have Four Fused Carbon Rings
BOX 10-1 MEDICINE Abnormal Accumulations of Membrane Lipids: Some Inherited Human Diseases
10.3. Lipids as Signals, Cofactors, and Pigments
Phosphatidylinositols and Sphingosine Derivatives Act as Intracellular Signals
Eicosanoids Carry Messages to Nearby Cells
Steroid Hormones Carry Messages between Tissues
Vascular Plants Produce Thousands of Volatile Signals
Vitamins A and D Are Hormone Precursors
Vitamins E and K and the Lipid Quinones Are Oxidation-Reduction Cofactors
Dolichols Activate Sugar Precursors for Biosynthesis
Many Natural Pigments Are Lipidic Conjugated Dienes
Polyketides Are Natural Products with Potent Biological Activities
10.4. Working with Lipids
Lipid Extraction Requires Organic Solvents
Adsorption Chromatography Separates Lipids of Different Polarity
Gas Chromatography Resolves Mixtures of Volatile Lipid Derivatives
Specific Hydrolysis Aids in Determination of Lipid Structure
Mass Spectrometry Reveals Complete Lipid Structure
Lipidomics Seeks to Catalog All Lipids and Their Functions
11. Biological Membranes and Transport
11.1. Composition and Architecture of Membranes
Each Type of Membrane Has Characteristic Lipids and Proteins
All Biological Membranes Share Some Fundamental Properties
Lipid Bilayer Is the Basic Structural Element of Membranes
Three Types of Membrane Proteins Differ in the Nature of Their Association with the Membrane
Many Integral Membrane Proteins Span the Lipid Bilayer
Hydrophobic Regions of Integral Proteins Associate with Membrane Lipids
Topology of an Integral Membrane Protein Can Often Be Predicted from Its Sequence
Covalently Attached Lipids Anchor Some Membrane Proteins
Amphitropic Proteins Associate Reversibly with the Membrane
11.2. Membrane Dynamics
Acyl Groups in the Bilayer Interior Are Ordered to Varying Degrees
Transbilayer Movement of Lipids Requires Catalysis
Lipids and Proteins Diffuse Laterally in the Bilayer
Sphingolipids and Cholesterol Cluster Together in Membrane Rafts
Membrane Curvature and Fusion Are Central to Many Biological Processes
Integral Proteins of the Plasma Membrane Are Involved in Surface Adhesion, Signaling, and Other Cellular Processes
11.3. Solute Transport across Membranes
Transport May Be Passive or Active
Transporters and Ion Channels Share Some Structural Properties but Have Different Mechanisms
Contents note continued: Glucose Transporter of Erythrocytes Mediates Passive Transport
Chloride-Bicarbonate Exchanger Catalyzes Electroneutral Cotransport of Anions across the Plasma Membrane
BOX 11-1 MEDICINE Defective Glucose and Water Transport in Two Forms of Diabetes
Active Transport Results in Solute Movement against a Concentration or Electrochemical Gradient
P-Type ATPases Undergo Phosphorylation during Their Catalytic Cycles
V-Type and F-Type ATPases Are ATP-Driven Proton Pumps
ABC Transporters Use ATP to Drive the Active Transport of a Wide Variety of Substrates
Ion Gradients Provide the Energy for Secondary Active Transport
BOX 11-2 MEDICINE A Defective Ion Channel in Cystic Fibrosis
Aquaporins Form Hydrophilic Transmembrane Channels for the Passage of Water
Ion-Selective Channels Allow Rapid Movement of Ions across Membranes
Ion-Channel Function Is Measured Electrically
Structure of a K+ Channel Reveals the Basis for Its Specificity
Gated Ion Channels Are Central in Neuronal Function
Defective Ion Channels Can Have Severe Physiological Consequences
12. Biosignaling
12.1. General Features of Signal Transduction
12.2. G Protein
Coupled Receptors and Second Messengers
β-Adrenergic Receptor System Acts through the Second Messenger cAMP
BOX 12-1 G Proteins: Binary Switches in Health and Disease
Several Mechanisms Cause Termination of the β-Adrenergic Response
0-Adrenergic Receptor Is Desensitized by Phosphorylation and by Association with Arrestin
Cyclic AMP Acts as a Second Messenger for Many Regulatory Molecules
Diacylglycerol, Inositol Trisphosphate, and Ca2+ Have Related Roles as Second Messengers
BOX 12-2 METHODS FRET: Biochemistry Visualized in a Living Cell
Calcium Is a Second Messenger That Is Localized in Space and Time
12.3. GPCRs in Vision, Olfaction, and Gustation
Vertebrate Eye Uses Classic GPCR Mechanisms
BOX 12-3 MEDICINE Color Blindness: John Dalton's Experiment from the Grave
Vertebrate Olfaction and Gustation Use Mechanisms Similar to the Visual System
All GPCR Systems Share Universal Features
12.4. Receptor Tyrosine Kinases
Stimulation of the Insulin Receptor Initiates a Cascade of Protein Phosphorylation Reactions
Membrane Phospholipid PIP3 Functions at a Branch in Insulin Signaling
Cross Talk among Signaling Systems Is Common and Complex
12.5. Receptor Guanylyl Cyclases, cGMP, and Protein Kinase G
12.6. Multivalent Adaptor Proteins and Membrane Rafts
Protein Modules Bind Phosphorylated Tyr, Ser, or Thr Residues in Partner Proteins
Membrane Rafts and Caveolae Segregate Signaling Proteins
12.7. Gated Ion Channels
Ion Channels Underlie Electrical Signaling in Excitable Cells
Voltage-Gated Ion Channels Produce Neuronal Action Potentials
Neurons Have Receptor Channels That Respond to Different Neurotransmitters
Toxins Target Ion Channels
12.8. Regulation of Transcription by Nuclear Hormone Receptors
12.9. Signaling in Microorganisms and Plants
Bacterial Signaling Entails Phosphorylation in a Two-Component System
Signaling Systems of Plants Have Some of the Same Components Used by Microbes and Mammals
12.10. Regulation of the Cell Cycle by Protein Kinases
Cell Cycle Has Four Stages
Levels of Cyclin-Dependent Protein Kinases Oscillate
CDKs Regulate Cell Division by Phosphorylating Critical Proteins
12.11. Oncogenes, Tumor Suppressor Genes, and Programmed Cell Death
Oncogenes Are Mutant Forms of the Genes for Proteins That Regulate the Cell Cycle
BOX 12-3 MEDICINE Development of Protein Kinase Inhibitors for Cancer Treatment
Defects in Certain Genes Remove Normal Restraints on Cell Division
Apoptosis Is Programmed Cell Suicide
II. BIOENERGETICS AND METABOLISM
13. Bioenergetics and Biochemical Reaction Types
13.1. Bioenergetics and Thermodynamics
Biological Energy Transformations Obey the Laws of Thermodynamics
Cells Require Sources of Free Energy
Standard Free-Energy Change Is Directly Related to the Equilibrium Constant
Actual Free-Energy Changes Depend on Reactant and Product Concentrations
Standard Free-Energy Changes Are Additive
13.2. Chemical Logic and Common Biochemical Reactions
Biochemical and Chemical Equations Are Not Identical
13.3. Phosphoryl Group Transfers and ATP
Free-Energy Change for ATP Hydrolysis Is Large and Negative
Other Phosphorylated Compounds and Thioesters Also Have Large Free Energies of Hydrolysis
ATP Provides Energy by Group Transfers, Not by Simple Hydrolysis
ATP Donates Phosphoryl, Pyrophosphoryl, and Adenylyl Groups
Assembly of Informational Macromolecules Requires Energy
ATP Energizes Active Transport and Muscle Contraction
BOX 13-1 Firefly Flashes: Glowing Reports of ATP
Transphosphorylations between Nucleotides Occur in All Cell Types
Inorganic Polyphosphate Is a Potential Phosphoryl Group Donor
13.4. Biological Oxidation-Reduction Reactions
Flow of Electrons Can Do Biological Work
Oxidation-Reductions Can Be Described as Half-Reactions
Biological Oxidations Often Involve Dehydrogenation
Reduction Potentials Measure Affinity for Electrons
Standard Reduction Potentials Can Be Used to Calculate Free-Energy Change
Cellular Oxidation of Glucose to Carbon Dioxide Requires Specialized Electron Carriers
Few Types of Coenzymes and Proteins Serve as Universal Electron Carriers
NADH and NADPH Act with Dehydrogenases as Soluble Electron Carriers
NAD Has Important Functions in Addition to Electron Transfer
Dietary Deficiency of Niacin, the Vitamin Form of NAD and NADP, Causes Pellagra
Flavin Nucleotides Are Tightly Bound in Flavoproteins
14. Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway
14.1. Glycolysis
Overview: Glycolysis Has Two Phases
Preparatory Phase of Glycolysis Requires ATP
Payoff Phase of Glycolysis Yields ATP and NADH
Overall Balance Sheet Shows a Net Gain of ATP
Glycolysis Is under Tight Regulation
BOX 14-1 MEDICINE High Rate of Glycolysis in Tumors Suggests Targets for Chemotherapy and Facilitates Diagnosis
Glucose Uptake Is Deficient in Type
Diabetes Mellitus
14.2. Feeder Pathways for Glycolysis
Dietary Polysaccharides and Disaccharides Undergo Hydrolysis to Monosaccharides
Endogenous Glycogen and Starch Are Degraded by Phosphorolysis
Other Monosaccharides Enter the Glycolytic Pathway at Several Points
14.3. Fates of Pyruvate under Anaerobic Conditions: Fermentation
Pyruvate Is the Terminal Electron Acceptor in Lactic Acid Fermentation
BOX 14-2 Athletes, Alligators, and Coelacanths: Glycolysis at Limiting Concentrations of Oxygen
Ethanol Is the Reduced Product in Ethanol Fermentation
Thiamine Pyrophosphate Carries "Active Acetaldehyde" Groups
BOX 14-3 Ethanol Fermentations: Brewing Beer and Producing Biofuels
Fermentations Are Used to Produce Some Common Foods and Industrial Chemicals
14.4. Gluconeogenesis
Conversion of Pyruvate to Phosphoenolpyruvate Requires Two Exergonic Reactions
Conversion of Fructose 1,6-Bisphosphate to Fructose 6-Phosphate Is the Second Bypass
Conversion of Glucose 6-Phosphate to Glucose Is the Third Bypass
Gluconeogenesis Is Energetically Expensive, but Essential
Citric Acid Cycle Intermediates and Some Amino Acids Are Glucogenic
Mammals Cannot Convert Fatty Acids to Glucose
Glycolysis and Gluconeogenesis Are Reciprocally Regulated
14.5. Pentose Phosphate Pathway of Glucose Oxidation
Oxidative Phase Produces Pentose Phosphates and NADPH
BOX 14-3 MEDICINE Why Pythagoras Wouldn't Eat Falafel: Glucose 6-Phosphate Dehydrogenase Deficiency
Nonoxidative Phase Recycles Pentose Phosphates to Glucose 6-Phosphate
Wernicke-Korsakoff Syndrome Is Exacerbated by a Defect in Transketolase
Glucose 6-Phosphate Is Partitioned between Glycolysis and the Pentose Phosphate Pathway
15. Principles of Metabolic Regulation
15.1. 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
Reactions Far from Equilibrium in Cells Are Common Points of Regulation
Adenine Nucleotides Play Special Roles in Metabolic Regulation
15.2. Analysis of Metabolic Control
Contribution of Each Enzyme to Flux through a Pathway Is Experimentally Measurable
Flux Control Coefficient Quantifies the Effect of a Change in Enzyme Activity on Metabolite Flux through a Pathway
Elasticity Coefficient Is Related to an Enzyme's Responsiveness to Changes in Metabolite or Regulator Concentrations
BOX 15-1 METHODS Metabolic Control Analysis: Quantitative Aspects
Response Coefficient Expresses the Effect of an Outside Controller on Flux through a Pathway
Metabolic Control Analysis Has Been Applied to Carbohydrate Metabolism, with Surprising Results
Metabolic Control Analysis Suggests a General Method for Increasing Flux through a Pathway
15.3. Coordinated Regulation of Glycolysis and Gluconeogenesis
Hexokinase Isozymes of Muscle and Liver Are Affected Differently by Their Product, Glucose 6-Phosphate
BOX 15.2 Isozymes: Different Proteins That Catalyze the Same Reaction
Hexokinase IV (Glucokinase) and Glucose 6-Phosphatase Are Transcriptionally Regulated
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
Xylulose 5-Phosphate Is a Key Regulator of Carbohydrate and Fat Metabolism
Contents note continued: Glycolytic Enzyme Pyruvate Kinase Is Allosterically Inhibited by ATP
Gluconeogenic Conversion of Pyruvate to Phosphoenolpyruvate Is under Multiple Types of Regulation
Transcriptional Regulation of Glycolysis and Gluconeogenesis Changes the Number of Enzyme Molecules
BOX 15-2 MEDICINE Genetic Mutations That Lead to Rare Forms of Diabetes
15.4. Metabolism of Glycogen in Animals
Glycogen Breakdown Is Catalyzed by Glycogen Phosphorylase
Glucose 1-Phosphate Can Enter Glycolysis or, in Liver, Replenish Blood Glucose
Sugar Nucleotide UDP-Glucose Donates Glucose for Glycogen Synthesis
BOX 15-3 Carl and Gerty Cori: Pioneers in Glycogen Metabolism and Disease
Glycogenin Primes the Initial Sugar Residues in Glycogen
15.5. Coordinated Regulation of Glycogen Breakdown and Synthesis
Glycogen Phosphorylase Is Regulated Allosterically and Hormonally
Glycogen Synthase Is Also Regulated by Phosphorylation and Dephosphorylation
Glycogen Synthase Kinase 3 Mediates Some of the Actions of Insulin
Phosphoprotein Phosphatase 1 Is Central to Glycogen Metabolism
Allosteric and Hormonal Signals Coordinate Carbohydrate Metabolism Globally
Carbohydrate and Lipid Metabolism Are Integrated by Hormonal and Allosteric Mechanisms
16. Citric Acid Cycle
16.1. Production of Acetyl-CoA (Activated Acetate)
Pyruvate Is Oxidized to Acetyl-CoA and CO2
Pyruvate Dehydrogenase Complex Employs Five Coenzymes
Pyruvate Dehydrogenase Complex Consists of Three Distinct Enzymes
In Substrate Channeling, Intermediates Never Leave the Enzyme Surface
16.2. Reactions of the Citric Acid Cycle
Sequence of Reactions in the Citric Acid Cycle Makes Chemical Sense
Citric Acid Cycle Has Eight Steps
BOX 16-1 Moonlighting Enzymes: Proteins with More Than One Job
BOX 16-2 Synthases and Synthetases; Ligases and Lyases; Kinases, Phosphatases, and Phosphorylases: Yes, the Names Are Confusing!
Energy of Oxidations in the Cycle Is Efficiently Conserved
BOX 15-3 Citrate: A Symmetric Molecule That Reacts Asymmetrically
Why Is the Oxidation of Acetate So Complicated?
Citric Acid Cycle Components Are Important Biosynthetic Intermediates
Anaplerotic Reactions Replenish Citric Acid Cycle Intermediates
Biotin in Pyruvate Carboxylase Carries CO2 Groups
16.3. Regulation of the Citric Acid Cycle
Production of Acetyl-CoA by the Pyruvate Dehydrogenase Complex Is Regulated by Allosteric and Covalent Mechanisms
Citric Acid Cycle Is Regulated at Its Three Exergonic Steps
Substrate Channeling through Multienzyme Complexes May Occur in the Citric Acid Cycle
Some Mutations in Enzymes of the Citric Acid Cycle Lead to Cancer
17. Fatty Acid Catabolism
17.1. Digestion, Mobilization, and Transport of Fats
Dietary Fats Are Absorbed in the Small Intestine
Hormones Trigger Mobilization of Stored Triacylglycerols
Fatty Acids Are Activated and Transported into Mitochondria
17.2. Oxidation of Fatty Acids
β Oxidation of Saturated Fatty Acids Has Four Basic Steps
Four β-Oxidation Steps Are Repeated to Yield Acetyl-CoA and ATP
Acetyl-CoA Can Be Further Oxidized in the Citric Acid Cycle
BOX 17-1 Long Winter's Nap: Oxidizing Fats during Hibernation
Oxidation of Unsaturated Fatty Acids Requires Two Additional Reactions
Complete Oxidation of Odd-Number Fatty Acids Requires Three Extra Reactions
Fatty Acid Oxidation Is Tightly Regulated
BOX 17-2 Coenzyme B12: A Radical Solution to a Perplexing Problem
Transcription Factors Turn on the Synthesis of Proteins for Lipid Catabolism
Genetic Defects in Fatty Acyl-CoA Dehydrogenases Cause Serious Disease
Peroxisomes Also Carry Out β Oxidation
β-Oxidation Enzymes of Different Organelles Have Diverged during Evolution
w Oxidation of Fatty Acids Occurs in the Endoplasmic Reticulum
Phytanic Acid Undergoes a Oxidation in Peroxisomes
17.3. Ketone Bodies
Ketone Bodies, Formed in the Liver, Are Exported to Other Organs as Fuel
Ketone Bodies Are Overproduced in Diabetes and during Starvation
18. Amino Acid Oxidation and the Production of Urea
18.1. Metabolic Fates of Amino Groups
Dietary Protein Is Enzymatically Degraded to Amino Acids
Pyridoxal Phosphate Participates in the Transfer of Q-Amino Groups to a-Ketoglutarate
Glutamate Releases Its Amino Group as Ammonia in the Liver
Glutamine Transports Ammonia in the Bloodstream
Alanine Transports Ammonia from Skeletal Muscles to the Liver
Ammonia Is Toxic to Animals
18.2. Nitrogen Excretion and the Urea Cycle
Urea Is Produced from Ammonia in Five Enzymatic Steps
Citric Acid and Urea Cycles Can Be Linked
Activity of the Urea Cycle Is Regulated at Two Levels
BOX 18-1 MEDICINE Assays for Tissue Damage
Pathway Interconnections Reduce the Energetic Cost of Urea Synthesis
Genetic Defects in the Urea Cycle Can Be Life-Threatening
18.3. Pathways of Amino Acid Degradation
Some Amino Acids Are Converted to Glucose, Others to Ketone Bodies
Several Enzyme Cofactors Play Important Roles in Amino Acid Catabolism
Six Amino Acids Are Degraded to Pyruvate
Seven Amino Acids Are Degraded to Acetyl-CoA
Phenylalanine Catabolism Is Genetically Defective in Some People
Five Amino Acids Are Converted to a-Ketoglutarate
Four Amino Acids Are Converted to Succinyl-CoA
Branched-Chain Amino Acids Are Not Degraded in the Liver
Asparagine and Aspartate Are Degraded to Oxaloacetate
BOX 18-2 MEDICINE Scientific Sleuths Solve a Murder Mystery
19. Oxidative Phosphorylation
19.1. Mitochondrial Respiratory Chain
Electrons Are Funneled to Universal Electron Acceptors
Electrons Pass through a Series of Membrane-Bound Carriers
Electron Carriers Function in Multienzyme Complexes
Mitochondrial Complexes Associate in Respirasomes
Other Pathways Donate Electrons to the Respiratory Chain via Ubiquinone
BOX 19-1 METHODS Determining Three-Dimensional Structures of Large Macromolecular Complexes by Single-Particle Cryo-Electron Microscopy
Energy of Electron Transfer Is Efficiently Conserved in a Proton Gradient
Reactive Oxygen Species Are Generated during Oxidative Phosphorylation
Plant Mitochondria Have Alternative Mechanisms for Oxidizing NADH
BOX 19-2 Hot, Stinking Plants and Alternative Respiratory Pathways
19.2. ATP Synthesis
In the Chemiosmotic Model, Oxidation and Phosphorylation Are Obligately Coupled
ATP Synthase Has Two Functional Domains, F0 and F1
ATP Is Stabilized Relative to ADP on the Surface of F1
Proton Gradient Drives the Release of ATP from the Enzyme Surface
Each β Subunit of ATP Synthase Can Assume Three Different Conformations
Rotational Catalysis Is Key to the Binding-Change Mechanism for ATP Synthesis
How Does Proton Flow through the F1 Complex Produce Rotary Motion?
BOX 19-2 Atomic Force Microscopy to Visualize Membrane Proteins
Chemiosmotic Coupling Allows Nonintegral Stoichiometries of O2 Consumption and ATP Synthesis
Proton-Motive Force Energizes Active Transport
Shuttle Systems Indirectly Convey Cytosolic NADH into Mitochondria for Oxidation
19.3. Regulation of Oxidative Phosphorylation
Oxidative Phosphorylation Is Regulated by Cellular Energy Needs
Inhibitory Protein Prevents ATP Hydrolysis during Hypoxia
Hypoxia Leads to ROS Production and Several Adaptive Responses
ATP-Producing Pathways Are Coordinately Regulated
19.4. Mitochondria in Thermogenesis, Steroid Synthesis, and Apoptosis
Uncoupled Mitochondria in Brown Adipose Tissue Produce Heat
Mitochondrial P-450 Monooxygenases Catalyze Steroid Hydroxylations
Mitochondria Are Central to the Initiation of Apoptosis
19.5. Mitochondrial Genes: Their Origin and the Effects of Mutations
Mitochondria Evolved from Endosymbiotic Bacteria
Mutations in Mitochondrial DNA Accumulate throughout the Life of the Organism
Some Mutations in Mitochondrial Genomes Cause Disease
Rare Form of Diabetes Results from Defects in the Mitochondria of Pancreatic β Cells
20. Photosynthesis and Carbohydrate Synthesis in Plants
20.1. Light Absorption
Chloroplasts Are the Site of Light-Driven Electron Flow and Photosynthesis in Plants
Chlorophylls Absorb Light Energy for Photosynthesis
Accessory Pigments Extend the Range of Light Absorption
Chlorophylls Funnel Absorbed Energy to Reaction Centers by Exciton Transfer
20.2. Photochemical Reaction Centers
Photosynthetic Bacteria Have Two Types of Reaction Center
Kinetic and Thermodynamic Factors Prevent the Dissipation of Energy by Internal Conversion
In Plants, Two Reaction Centers Act in Tandem
Cytochrome b6f Complex Links Photosystems II and I
Cyclic Electron Flow between PSI and the Cytochrome b6f Complex Increases the Production of ATP Relative to NADPH
State Transitions Change the Distribution of LHCII between the Two Photosystems
Water Is Split by the Oxygen-Evolving Complex
20.3. ATP Synthesis by Photophosphorylation
Proton Gradient Couples Electron Flow and Phosphorylation
Approximate Stoichiometry of Photophosphorylation Has Been Established
ATP Synthase of Chloroplasts Resembles That of Mitochondria
20.4. Evolution of Oxygenic Photosynthesis
Chloroplasts Evolved from Ancient Photosynthetic Bacteria
In Halobacterium, a Single Protein Absorbs Light and Pumps Protons to Drive ATP Synthesis
20.5. Carbon-Assimilation Reactions
Carbon Dioxide Assimilation Occurs in Three Stages
Contents note continued: Synthesis of Each Triose Phosphate from CO2 Requires Six NADPH and Nine ATP
Transport System Exports Triose Phosphates from the Chloroplast and Imports Phosphate
Four Enzymes of the Calvin Cycle Are Indirectly Activated by Light
20.6. Photorespiration and the C4 and CAM Pathways
Photorespiration Results from Rubisco's Oxygenase Activity
Salvage of Phosphoglycolate Is Costly
In C4 Plants, CO2 Fixation and Rubisco Activity Are Spatially Separated
BOX 20-1 Will Genetic Engineering of Photosynthetic Organisms Increase Their Efficiency?
In CAM Plants, CO2 Capture and Rubisco Action Are Temporally Separated
20.7. Biosynthesis of Starch, Sucrose, and Cellulose
ADP-Glucose Is the Substrate for Starch Synthesis in Plant Plastids and for Glycogen Synthesis in Bacteria
UDP-Glucose Is the Substrate for Sucrose Synthesis in the Cytosol of Leaf Cells
Conversion of Triose Phosphates to Sucrose and Starch Is Tightly Regulated
Glyoxylate Cycle and Gluconeogenesis Produce Glucose in Germinating Seeds
Cellulose Is Synthesized by Supramolecular Structures in the Plasma Membrane
20.8. Integration of Carbohydrate Metabolism in Plants
Pools of Common Intermediates Link Pathways in Different Organelles
21. Lipid Biosynthesis
21.1. Biosynthesis of Fatty Acids and Eicosanoids
Malonyl-CoA Is Formed from Acetyl-CoA and Bicarbonate
Fatty Acid Synthesis Proceeds in a Repeating Reaction Sequence
Mammalian Fatty Acid Synthase Has Multiple Active Sites
Fatty Acid Synthase Receives the Acetyl and Malonyl Groups
Fatty Acid Synthase Reactions Are Repeated to Form Palmitate
Fatty Acid Synthesis Is a Cytosolic Process in Many Organisms but Takes Place in the Chloroplasts in Plants
Acetate Is Shuttled out of Mitochondria as Citrate
Fatty Acid Biosynthesis Is Tightly Regulated
Long-Chain Saturated Fatty Acids Are Synthesized from Palmitate
Desaturation of Fatty Acids Requires a Mixed-Function Oxidase
BOX 21-1 MEDICINE Oxidases, Oxygenases, Cytochrome P-450 Enzymes, and Drug Overdoses
Eicosanoids Are Formed from 20- and 22-Carbon Polyunsaturated Fatty Acids
21.2. Biosynthesis of Triacylglycerols
Triacylglycerols and Glycerophospholipids Are Synthesized from the Same Precursors
Triacylglycerol Biosynthesis in Animals Is Regulated by Hormones
Adipose Tissue Generates Glycerol 3-Phosphate by Glyceroneogenesis
Thiazolidinediones Treat Type 2 Diabetes by Increasing Glyceroneogenesis
21.3. Biosynthesis of Membrane Phospholipids
Cells Have Two Strategies for Attaching Phospholipid Head Groups
Phospholipid Synthesis in E. coli Employs CDP-Diacylglycerol
Eukaryotes Synthesize Anionic Phospholipids from CDP-Diacylglycerol
Eukaryotic Pathways to Phosphatidylserine, Phosphatidylethanolamine, and Phosphatidylcholine Are Interrelated
Plasmalogen Synthesis Requires Formation of an Ether-Linked Fatty Alcohol
Sphingolipid and Glycerophospholipid Synthesis Share Precursors and Some Mechanisms
Polar Lipids Are Targeted to Specific Cellular Membranes
21.4. Cholesterol, Steroids, and Isoprenoids: Biosynthesis, Regulation, and Transport
Cholesterol Is Made from Acetyl-CoA in Four Stages
Cholesterol Has Several Fates
Cholesterol and Other Lipids Are Carried on Plasma Lipoproteins
BOX 21-2 MEDICINE ApoE Alleles Predict Incidence of Alzheimer Disease
Cholesteryl Esters Enter Cells by Receptor-Mediated Endocytosis
HDL Carries Out Reverse Cholesterol Transport
Cholesterol Synthesis and Transport Are Regulated at Several Levels
Dysregulation of Cholesterol Metabolism Can Lead to Cardiovascular Disease
Reverse Cholesterol Transport by HDL Counters Plaque Formation and Atherosclerosis
BOX 21-3 MEDICINE The Lipid Hypothesis and the Development of Statins
Steroid Hormones Are Formed by Side-Chain Cleavage and Oxidation of Cholesterol
Intermediates in Cholesterol Biosynthesis Have Many Alternative Fates
22. Biosynthesis of Amino Acids, Nucleotides, and Related Molecules
22.1. Overview of Nitrogen Metabolism
Nitrogen Cycle Maintains a Pool of Biologically Available Nitrogen
Nitrogen Is Fixed by Enzymes of the Nitrogenase Complex
BOX 22-1 Unusual Lifestyles of the Obscure but Abundant
Ammonia Is Incorporated into Biomolecules through Glutamate and Glutamine
Glutamine Synthetase Is a Primary Regulatory Point in Nitrogen Metabolism
Several Classes of Reactions Play Special Roles in the Biosynthesis of Amino Acids and Nucleotides
22.2. Biosynthesis of Amino Acids
α-Ketoglutarate Gives Rise to Glutamate, Glutamine, Proline, and Arginine
Serine, Glycine, and Cysteine Are Derived from 3-Phosphoglycerate
Three Nonessential and Six Essential Amino Acids Are Synthesized from Oxaloacetate and Pyruvate
Chorismate Is a Key Intermediate in the Synthesis of Tryptophan, Phenylalanine, and Tyrosine
Histidine Biosynthesis Uses Precursors of Purine Biosynthesis
Amino Acid Biosynthesis Is under Allosteric Regulation
22.3. Molecules Derived from Amino Acids
Glycine Is a Precursor of Porphyrins
Heme Degradation Has Multiple Functions
BOX 22-1 MEDICINE On Kings and Vampires
Amino Acids Are Precursors of Creatine and Glutathione
D-Amino Acids Are Found Primarily in Bacteria
Aromatic Amino Acids Are Precursors of Many Plant Substances
Biological Amines Are Products of Amino Acid Decarboxylation
Arginine Is the Precursor for Biological Synthesis of Nitric Oxide
22.4. Biosynthesis and Degradation of Nucleotides
De Novo Purine Nucleotide Synthesis Begins with PRPP
Purine Nucleotide Biosynthesis Is Regulated by Feedback Inhibition
Pyrimidine Nucleotides Are Made from Aspartate, PRPP, and Carbamoyl Phosphate
Pyrimidine Nucleotide Biosynthesis Is Regulated by Feedback Inhibition
Nucleoside Monophosphates Are Converted to Nucleoside Triphosphates
Ribonucleotides Are the Precursors of Deoxyribonucleotides
Thymidylate Is Derived from dCDP and dUMP
Degradation of Purines and Pyrimidines Produces Uric Acid and Urea, Respectively
Purine and Pyrimidine Bases Are Recycled by Salvage Pathways
Excess Uric Acid Causes Gout
Many Chemotherapeutic Agents Target Enzymes in Nucleotide Biosynthetic Pathways
23. Hormonal Regulation and Integration of Mammalian Metabolism
23.1. Hormones: Diverse Structures for Diverse Functions
Detection and Purification of Hormones Requires a Bioassay
BOX 23-1 MEDICINE How Is a Hormone Discovered? The Arduous Path to Purified Insulin
Hormones Act through Specific High-Affinity Cellular Receptors
Hormones Are Chemically Diverse
Hormone Release Is Regulated by a "Top-Down" Hierarchy of Neuronal and Hormonal Signals
"Bottom-Up" Hormonal Systems Send Signals Back to the Brain and to Other Tissues
23.2. Tissue-Specific Metabolism: The Division of Labor
Liver Processes and Distributes Nutrients
Adipose Tissues Store and Supply Fatty Acids
Brown and Beige Adipose Tissues Are Thermogenic
Muscles Use ATP for Mechanical Work
BOX 23-2 Creatine and Creatine Kinase: Invaluable Diagnostic Aids and the Muscle Builder's Friends
Brain Uses Energy for Transmission of Electrical Impulses
Blood Carries Oxygen, Metabolites, and Hormones
23.3. Hormonal Regulation of Fuel Metabolism
Insulin Counters High Blood Glucose
Pancreatic β Cells Secrete Insulin in Response to Changes in Blood Glucose
Glucagon Counters Low Blood Glucose
During Fasting and Starvation, Metabolism Shifts to Provide Fuel for the Brain
Epinephrine Signals Impending Activity
Cortisol Signals Stress, Including Low Blood Glucose
Diabetes Mellitus Arises from Defects in Insulin Production or Action
23.4. Obesity and the Regulation of Body Mass
Adipose Tissue Has Important Endocrine Functions
Leptin Stimulates Production of Anorexigenic Peptide Hormones
Leptin Triggers a Signaling Cascade That Regulates Gene Expression
Leptin System May Have Evolved to Regulate the Starvation Response
Insulin Also Acts in the Arcuate Nucleus to Regulate Eating and Energy Conservation
Adiponectin Acts through AMPK to Increase Insulin Sensitivity
AMPK Coordinates Catabolism and Anabolism in Response to Metabolic Stress
mTORC1 Pathway Coordinates Cell Growth with the Supply of Nutrients and Energy
Diet Regulates the Expression of Genes Central to Maintaining Body Mass
Short-Term Eating Behavior Is Influenced by Ghrelin, PYY3-36, and Cannabinoids
Microbial Symbionts in the Gut Influence Energy Metabolism and Adipogenesis
23.5. Obesity, Metabolic Syndrome, and Type 2 Diabetes
In Type 2 Diabetes the Tissues Become Insensitive to Insulin
Type 2 Diabetes Is Managed with Diet, Exercise, Medication, and Surgery
III. INFORMATION PATHWAYS
24. Genes and Chromosomes
24.1. Chromosomal Elements
Genes Are Segments of DNA That Code for Polypeptide Chains and RNAs
DNA Molecules Are Much Longer Than the Cellular or Viral Packages That Contain Them
Eukaryotic Genes and Chromosomes Are Very Complex
24.2. DNA Supercoiling
Most Cellular DNA Is Underwound
DNA Underwinding Is Defined by Topological Linking Number
Topoisomerases Catalyze Changes in the Linking Number of DNA
BOX 24-1 MEDICINE Curing Disease by Inhibiting Topoisomerases
DNA Compaction Requires a Special Form of Supercoiling
24.3. Structure of Chromosomes
Chromatin Consists of DNA and Proteins
Histones Are Small, Basic Proteins
Nucleosomes Are the Fundamental Organizational Units of Chromatin
Contents note continued: Nucleosomes Are Packed into Highly Condensed Chromosome Structures
BOX 24-2 METHODS Epigenetics, Nucleosome Structure, and Histone Variants
Condensed Chromosome Structures Are Maintained by SMC Proteins
Bacterial DNA Is Also Highly Organized
25. DNA Metabolism
25.1. DNA Replication
DNA Replication Follows a Set of Fundamental Rules
DNA Is Degraded by Nucleases
DNA Is Synthesized by DNA Polymerases
Replication Is Very Accurate
E. coli Has at Least Five DNA Polymerases
DNA Replication Requires Many Enzymes and Protein Factors
Replication of the E. coli Chromosome Proceeds in Stages
Replication in Eukaryotic Cells Is Similar but More Complex
Viral DNA Polymerases Provide Targets for Antiviral Therapy
25.2. DNA Repair
Mutations Are Linked to Cancer
All Cells Have Multiple DNA Repair Systems
Interaction of Replication Forks with DNA Damage Can Lead to Error-Prone Translesion DNA Synthesis
BOX 25-1 MEDICINE DNA Repair and Cancer
25.3. DNA Recombination
Bacterial Homologous Recombination Is a DNA Repair Function
Eukaryotic Homologous Recombination Is Required for Proper Chromosome Segregation during Meiosis
Recombination during Meiosis Is Initiated with Double-Strand Breaks
BOX 25-2 MEDICINE Why Proper Segregation of Chromosomes Matters
Some Double-Strand Breaks Are Repaired by Nonhomologous End Joining
Site-Specific Recombination Results in Precise DNA Rearrangements
Transposable Genetic Elements Move from One Location to Another
Immunoglobulin Genes Assemble by Recombination
26. RNA Metabolism
26.1. DNA-Dependent Synthesis of RNA
RNA Is Synthesized by RNA Polymerases
RNA Synthesis Begins at Promoters
Transcription Is Regulated at Several Levels
BOX 26-1 METHODS RNA Polymerase Leaves Its Footprint on a Promoter
Specific Sequences Signal Termination of RNA Synthesis
Eukaryotic Cells Have Three Kinds of Nuclear RNA Polymerases
RNA Polymerase II Requires Many Other Protein Factors for Its Activity
DNA-Dependent RNA Polymerase Undergoes Selective Inhibition
26.2. RNA Processing
Eukaryotic mRNAs Are Capped at the 5' End
Both Introns and Exons Are Transcribed from DNA into RNA
RNA Catalyzes the Splicing of Introns
Eukaryotic mRNAs Have a Distinctive 3' End Structure
Gene Can Give Rise to Multiple Products by Differential RNA Processing
Ribosomal RNAs and tRNAs Also Undergo Processing
Special-Function RNAs Undergo Several Types of Processing
RNA Enzymes Are the Catalysts of Some Events in RNA Metabolism
Cellular mRNAs Are Degraded at Different Rates
Polynucleotide Phosphorylase Makes Random RNA-like Polymers
26.3. RNA-Dependent Synthesis of RNA and DNA
Reverse Transcriptase Produces DNA from Viral RNA
Some Retroviruses Cause Cancer and AIDS
Many Transposons, Retroviruses, and Introns May Have a Common Evolutionary Origin
BOX 26.2 MEDICINE Fighting AIDS with Inhibitors of HIV Reverse Transcriptase
Telomerase Is a Specialized Reverse Transcriptase
Some RNAs Are Replicated by RNA-Dependent RNA Polymerase
RNA Synthesis Provides Clues to the Origin of Life in an RNA World
BOX 26-2 METHODS The SELEX Method for Generating RNA Polymers with New Functions
27. Protein Metabolism
27.1. Genetic Code
Genetic Code Was Cracked Using Artificial mRNA Templates
BOX 27-1 Exceptions That Prove the Rule: Natural Variations in the Genetic Code
Wobble Allows Some tRNAs to Recognize More than One Codon
Genetic Code Is Mutation-Resistant
Translational Frameshifting and RNA Editing Affect How the Code Is Read
27.2. Protein Synthesis
Protein Biosynthesis Takes Place in Five Stages
Ribosome Is a Complex Supramolecular Machine
Transfer RNAs Have Characteristic Structural Features
Stage 1 Aminoacyl-tRNA Synthetases Attach the Correct Amino Acids to Their tRNAs
Stage 2 Specific Amino Acid Initiates Protein Synthesis
BOX 27-2 Natural and Unnatural Expansion of the Genetic Code
Stage 3 Peptide Bonds Are Formed in the Elongation Stage
Stage 4 Termination of Polypeptide Synthesis Requires a Special Signal
Induced Variation in the Genetic Code: Nonsense Suppression
Stage 5 Newly Synthesized Polypeptide Chains Undergo Folding and Processing
Ribosome Profiling Provides a Snapshot of Cellular Translation
Protein Synthesis Is Inhibited by Many Antibiotics and Toxins
27.3. Protein Targeting and Degradation
Posttranslational Modification of Many Eukaryotic Proteins Begins in the Endoplasmic Reticulum
Glycosylation Plays a Key Role in Protein Targeting
Signal Sequences for Nuclear Transport Are Not Cleaved
Bacteria Also Use Signal Sequences for Protein Targeting
Cells Import Proteins by Receptor-Mediated Endocytosis
Protein Degradation Is Mediated by Specialized Systems in All Cells
28. Regulation of Gene Expression
28.1. Principles of Gene Regulation
RNA Polymerase Binds to DNA at Promoters
Transcription Initiation Is Regulated by Proteins and RNAs
Many Bacterial Genes Are Clustered and Regulated in Operons
lac Operon Is Subject to Negative Regulation
Regulatory Proteins Have Discrete DNA-Binding Domains
Regulatory Proteins Also Have Protein-Protein Interaction Domains
28.2. Regulation of Gene Expression in Bacteria
lac Operon Undergoes Positive Regulation
Many Genes for Amino Acid Biosynthetic Enzymes Are Regulated by Transcription Attenuation
Induction of the SOS Response Requires Destruction of Repressor Proteins
Synthesis of Ribosomal Proteins Is Coordinated with rRNA Synthesis
Function of Some mRNAs Is Regulated by Small RNAs in Cis or in Trans
Some Genes Are Regulated by Genetic Recombination
28.3. Regulation of Gene Expression in Eukaryotes
Transcriptionally Active Chromatin Is Structurally Distinct from Inactive Chromatin
Most Eukaryotic Promoters Are Positively Regulated
DNA-Binding Activators and Coactivators Facilitate Assembly of the Basal Transcription Factors
Genes of Galactose Metabolism in Yeast Are Subject to Both Positive and Negative Regulation
Transcription Activators Have a Modular Structure
Eukaryotic Gene Expression Can Be Regulated by Intercellular and Intracellular Signals
Regulation Can Result from Phosphorylation of Nuclear Transcription Factors
Many Eukaryotic mRNAs Are Subject to Translational Repression
Posttranscriptional Gene Silencing Is Mediated by RNA Interference
RNA-Mediated Regulation of Gene Expression Takes Many Forms in Eukaryotes
Development Is Controlled by Cascades of Regulatory Proteins
Stem Cells Have Developmental Potential That Can Be Controlled
BOX 28-1 Of Fins, Wings, Beaks, and Things.