Name: Marks' Basic Medical Biochemistry - Bókakaup
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Cover
Title Page
Copyright
Preface to the Sixth Edition
How to Use This Book
Acknowledgments
Reviewers
Contents
Animation
Section I: Fuel Metabolism
1 Metabolic Fuels and Dietary Components
I. Dietary Fuels
A. Carbohydrates
B. Proteins
C. Fats
D. Alcohol
II. Body Fuel Stores
A. Fat
B. Glycogen
C. Protein
III. Daily Energy Expenditure
A. Basal Metabolic Rate
B. Physical Activity
C. Diet-Induced Thermogenesis
D. Calculations of Daily Energy Expenditure
E. Healthy Body Weight
F. Weight Gain and Loss
IV. Dietary Requirements
A. Carbohydrates
B. Essential Fatty Acids
C. Protein
D. Vitamins
E. Minerals
F. Water
V. Dietary Guidelines
A. General Recommendations
B. Carbohydrates
C. Fats
D. Proteins
E. Alcohol
F. Vitamins and Minerals
VI. Xenobiotics
Chapter 1: Review Questions
2 The Fed or Absorptive State
I. Digestion and Absorption
A. Carbohydrates
B. Proteins
C. Fats
II. Changes in Hormone Levels after a Meal
III. Fate of Glucose
A. Conversion to Glycogen, Triacylglycerols, and CO2 in the Liver
B. Glucose Metabolism in Other Tissues
IV. Lipoproteins
V. Amino Acids
VI. Summary of the Fed (Absorptive) State
Chapter 2: Review Questions
3 Fasting
I. The Fasting State
A. Blood Glucose and the Role of the Liver during Fasting
B. Role of Adipose Tissue during Fasting
C. Summary of the Metabolic Changes during a Brief Fast
II. Metabolic Changes during Prolonged Fasting
A. Role of Liver during Prolonged Fasting
B. Role of Adipose Tissue during Prolonged Fasting
Chapter 3: Review Questions
Section II: Chemical and Biologic Foundations of Biochemistry
4 Water, Acids, Bases, and Buffers
I. Water
A. Fluid Compartments in the Body
B. Hydrogen Bonds in Water
C. Electrolytes
D. Osmolality and Water Movement
II. Acids and Bases
A. The pH of Water
B. Strong and Weak Acids
III. Buffers
IV. Metabolic Acids and Buffers
A. The Bicarbonate Buffer System
B. Bicarbonate and Hemoglobin in Red Blood Cells
C. Intracellular pH
D. Urinary Hydrogen, Ammonium, and Phosphate Ions
E. Hydrochloric Acid
Chapter 4: Review Questions
5 Structures of the Major Compounds of the Body
I. Functional Groups on Biologic Compounds
A. Biologic Compounds
B. Functional Groups
C. Polarity of Bonds and Partial Charges
D. Nomenclature
II. Carbohydrates
A. Monosaccharides
B. Glycosides
III. Lipids
A. Fatty Acids
B. Acylglycerols
C. Phosphoacylglycerols
D. Sphingolipids
E. Steroids
IV. Nitrogen-Containing Compounds
A. Amino Acids
B. Nitrogen-Containing Ring Structures
V. Free Radicals
Chapter 5: Review Questions
6 Amino Acids in Proteins
I. General Structure of the Amino Acids
II. Classification of Amino Acid Side Chains
A. Nonpolar, Aliphatic Amino Acids
B. Aromatic Amino Acids
C. Aliphatic, Polar, Uncharged Amino Acids
D. Sulfur-Containing Amino Acids
E. The Acidic and Basic Amino Acids
III. Variations in Primary Structure
A. Polymorphism in Protein Structure
B. Tissue and Developmental Variations in Protein Structure
C. Species Variations in the Primary Structure of Insulin
A. Protein Families and Superfamilies
B. Creatine Kinase and Myocardial Infarctions
IV. Modified Amino Acids
A. Glycosylation
B. Fatty Acylation or Prenylation
C. Regulatory Modifications
D. Other Amino Acid Posttranslational Modifications
E. Selenocysteine
Chapter 6: Review Questions
7 Structure–Function Relationships in Proteins
I. General Characteristics of Three-Dimensional Structure
A. Descriptions of Protein Structure
B. Requirements of the Three-Dimensional Structure
II. The Three-Dimensional Structure of the Peptide Backbone
III. Secondary Structure
A. The α-Helix
B. β-Sheets
C. Nonrepetitive Secondary Structures
D. Patterns of Secondary Structure
IV. Tertiary Structure
A. Domains in the Tertiary Structure
B. Folds in Globular Proteins
C. The Solubility of Globular Proteins in an Aqueous Environment
D. Tertiary Structure of Transmembrane Proteins
V. Quaternary Structure
VI. Quantitation of Ligand Binding
VII. Structure–Function Relationships in Myoglobin and Hemoglobin
A. Oxygen Binding and Heme
B. Cooperativity of O2 Binding in Hemoglobin
C. Agents That Affect Oxygen Binding
C. Carbon Dioxide
VIII. Structure–Function Relationships in Immunoglobulins
IX. Protein Folding
A. Primary Structure Determines Folding
B. Fibrous Proteins—Collagen
C. Protein Denaturation
Chapter 7: Review Questions
8 Enzymes as Catalysts
I. The Enzyme-Catalyzed Reaction
A. The Active Site
B. Substrate-Binding Sites
C. The Transition-State Complex
II. Strategies for Catalysis
A. General Acid–Base Catalysis
II. Catalytic Mechanism of Chymotrypsin
A. The Reaction in the Absence of Enzyme
B. Catalytic Strategies in the Reaction Catalyzed by Chymotrypsin
C. Energy Diagram in the Presence of Chymotrypsin
B. Covalent Catalysis
C. Metal-Ion Catalysis
D. Catalysis by Approximation
E. Cofactor Catalysis
III. Functional Groups in Catalysis
A. Functional Groups on Amino Acid Side Chains
B. Coenzymes in Catalysis
C. Metal Ions in Catalysis (See Also Section II.C)
D. Noncatalytic Roles of Cofactors
IV. Optimal pH and Temperature
V. Mechanism-Based Inhibitors
A. Covalent Inhibitors
B. Transition-State Analogs and Compounds That Resemble Intermediate Stages of the Reaction
C. Heavy Metals
Chapter 8: Review Questions
9 Regulation of Enzymes
I. General Overview
II. Regulation by Substrate and Product Concentration
A. Velocity and Substrate Concentration
B. Reversible Inhibition within the Active Site
III. Regulation through Conformational Changes
A. Conformational Changes in Allosteric Enzymes
B. Conformational Changes from Covalent Modification
C. Conformational Changes Regulated by Protein–Protein Interactions
D. Proteolytic Cleavage
IV. Regulation through Changes in Amount of Enzyme
A. Regulated Enzyme Synthesis
B. Regulated Protein Degradation
V. Regulation of Metabolic Pathways
A. Principles of Pathway Regulation
Chapter 9: Review Questions
10 Cell Structure and Signaling by Chemical Messengers
I. Compartmentation in Cells
II. Plasma Membrane
A. Structure of the Plasma Membrane
B. Transport of Molecules across the Plasma Membrane
III. Lysosomes
IV. Mitochondria
V. Peroxisomes
VI. Nucleus
VII. Endoplasmic Reticulum
VIII. Golgi Complex
IX. Cytoskeleton
X. General Features of Chemical Messengers
A. General Features of Chemical Messenger Systems Applied to the Nicotinic Acetylcholine Receptor
B. Endocrine, Paracrine, Autocrine, and Juxtacrine Actions
C. Types of Chemical Messengers
XI. Intracellular Transcription Factor Receptors
A. Intracellular versus Plasma Membrane Receptors
B. The Steroid Hormone/Thyroid Hormone Superfamily of Receptors
XII. Plasma Membrane Receptors and Signal Transduction
A. Ion-Channel Receptors
B. Receptors That Are Kinases or That Bind Kinases
C. Heptahelical Receptors
D. Juxtacrine Signaling
XIII. Signal Termination
Chapter 10: Review Questions
11 Structure of the Nucleic Acids
I. DNA Structure
A. Location of DNA
B. Determination of the Structure of DNA
C. Concept of Base Pairing
D. DNA Strands Are Antiparallel
E. The Double Helix
F. Characteristics of DNA
II. Structure of Chromosomes
A. Size of DNA Molecules
B. Packaging of DNA
C. The Human Genome
III. Structure of RNA
A. General Features of RNA
B. Structure of mRNA
C. Structure of rRNA
D. Structure of tRNA
E. Other Types of RNA
Chapter 11: Review Questions
Section III: Gene Expression and the Synthesis of Proteins
12 Synthesis of DNA
I. DNA Synthesis in Prokaryotes
A. Bidirectional Replication
B. Semiconservative Replication
C. DNA Unwinding
D. DNA Polymerase Action
E. Base-Pairing Errors
F. RNA Primer Requirement
G. The Replication Fork
H. DNA Ligase
II. DNA Synthesis in Eukaryotes
A. Eukaryotic Cell Cycle
B. Points of Origin for Replication
C. Eukaryotic DNA Polymerases
D. The Eukaryotic Replication Complex
E. Replication at the Ends of Chromosomes
III. DNA Repair
A. Actions of Mutagens
B. Repair Mechanisms
IV. Genetic Rearrangements
A. General or Homologous Recombination
B. Translocations
C. Repair of Single- and Double-Strand Breaks in DNA
D. Transposable Elements
V. Reverse Transcriptase
Chapter 12: Review Questions
13 Transcription: Synthesis of RNA
I. Action of RNA Polymerase
II. Types of RNA Polymerases
A. Sequences of Genes
B. Recognition of Genes by RNA Polymerase
C. Promoter Regions of Genes for mRNA
III. Transcription of Bacterial Genes
IV. Transcription of Eukaryotic Genes
A. Synthesis of Eukaryotic mRNA
B. Synthesis of Eukaryotic rRNA
C. Synthesis of Eukaryotic tRNA
V. Differences in Size between Eukaryotic and Prokaryotic DNA
A. Diploid versus Haploid
B. Introns
C. Repetitive Sequences in Eukaryotic DNA
D. Summary of the Differences between Eukaryotic and Prokaryotic DNA and RNA
Chapter 13: Review Questions
14 Translation: Synthesis of Proteins
I. The Genetic Code
A. The Code Is Degenerate Yet Unambiguous
B. The Code Is Nonoverlapping
C. Relationship between mRNA and the Protein Product
II. Effects of Mutations
A. Point Mutations
B. Insertions, Deletions, and Frameshift Mutations
III. Formation of Aminoacyl-tRNA
IV. Process of Translation
A. Initiation of Translation
B. Elongation of Polypeptide Chains
C. Termination of Translation
V. Polysomes
VI. Processing of Proteins
VII. Posttranslational Modifications
VIII. Targeting of Proteins to Subcellular and Extracellular Locations
Chapter 14: Review Questions
15 Regulation of Gene Expression
I. Gene Expression Is Regulated for Adaptation and Differentiation
II. Regulation of Gene Expression in Prokaryotes
A. Operons
B. Regulation of RNA Polymerase Binding by Repressors
C. Stimulation of RNA Polymerase Binding
D. Regulation of RNA Polymerase Binding by Sigma Factors
E. Attenuation of Transcription
III. Regulation of Gene Expression in Eukaryotes
A. Regulation at Multiple Levels
B. Regulation of Availability of Genes for Transcription
C. Regulation at the Level of Transcription
D. Posttranscriptional Processing of RNA
E. Regulation at the Level of Translation and the Stability of mRNA
F. Transport and Stability of mRNA
Chapter 15: Review Questions
16 Use of Recombinant DNA Techniques in Medicine
I. Recombinant DNA Techniques
A. Strategies for Obtaining Fragments of DNA and Copies of Genes
B. Techniques for Identifying DNA Sequences
C. Techniques for Amplifying DNA Sequences
II. Use of Recombinant DNA Techniques for Diagnosis of Disease
A. DNA Polymorphisms
B. Detection of Polymorphisms
III. Use of Recombinant DNA Techniques for the Prevention and Treatment of Disease
A. Vaccines
B. Production of Therapeutic Proteins
C. Small Interfering RNA (SiRNA)
D. Genetic Counseling
E. Gene Therapy
F. The CRISPR/Cas System
G. Transgenic Animals
IV. Proteomics
Chapter 16: Review Questions
17 The Molecular Biology of Cancer
I. Causes of Cancer
II. Damage to DNA Leading to Mutations
A. Chemical and Physical Alterations in DNA
B. Gain-of-Function Mutations in Proto-oncogenes
C. Mutations in Repair Enzymes
III. Oncogenes
A. Oncogenes and Signal Transduction Cascades
B. Oncogenes and the Cell Cycle
IV. Tumor-Suppressor Genes
A. Tumor-Suppressor Genes That Regulate the Cell Cycle Directly
B. Tumor-Suppressor Genes That Affect Receptors and Signal Transduction
C. Tumor-Suppressor Genes That Affect Cell Adhesion
D. Tumor-Suppressor Genes Linked to DNA Repair
V. Cancer and Apoptosis
A. Normal Pathways to Apoptosis
B. Cancer Cells Bypass Apoptosis
C. MicroRNAs and Apoptosis
VI. Cancer Requires Multiple Mutations
VII. At the Molecular Level, Cancer Is Many Different Diseases
VIII. Viruses and Human Cancer
Chapter 17: Review Questions
18 An Introduction to Human Genetics
I. Mendelian Inheritance Patterns
II. Genes
III. Mutations
IV. Inheritance Patterns
A. Autosomal Dominant Inheritance
B. Autosomal Recessive Inheritance
C. X-linked Inheritance
D. Mitochondrial Inheritance
V. Cytogenetics
A. Mitosis and Cell Division
B. Meiosis and Gamete Formation
C. Chromosome Structure and Nomenclature
D. Abnormalities of Chromosome Number
E. Abnormalities of Chromosome Structure
F. Prenatal Cytogenetics
VI. Population Genetics
VII. Multifactorial Diseases (Complex Traits)
VIII. Triplet Nucleotide Repeat Expansions
IX. Imprinting
X. Epigenetics
XI. The Genetics of Tumor Suppressors
Chapter 18: Review Questions
Section IV: Carbohydrate Metabolism, Fuel Oxidation, and the Generation of Adenosine Triphosphate
19 Basic Concepts in the Regulation of Fuel Metabolism by Insulin, Glucagon, and Other Hormones
I. Metabolic Homeostasis
II. Major Hormones of Metabolic Homeostasis
III. Synthesis and Release of Insulin and Glucagon
A. Endocrine Pancreas
B. Synthesis and Secretion of Insulin
C. Stimulation and Inhibition of Insulin Release
D. Synthesis and Secretion of Glucagon
IV. Mechanisms of Hormone Action
A. Signal Transduction by Hormones That Bind to Plasma Membrane Receptors
B. Signal Transduction by Cortisol and Other Hormones That Interact with Intracellular Receptors
C. Signal Transduction by Epinephrine and Norepinephrine
Chapter 19: Review Questions
20 Cellular Bioenergetics: Adenosine Triphosphate and O2
I. Energy Available to Do Work
A. The High-Energy Phosphate Bonds of ATP
B. Change in Free Energy (ΔG) during a Reaction
C. Exothermic and Endothermic Reactions
II. Energy Transformations to Do Mechanical and Transport Work
A. Mechanical Work
B. Transport Work
III. Biochemical Work
A. Adding ΔG0 Values
B. ΔG Depends on Substrate and Product Concentrations
C. Activated Intermediates with High-Energy Bonds
IV. Thermogenesis
V. Energy from Fuel Oxidation
A. Energy Transfer from Fuels through Oxidative Phosphorylation
B. NADPH in Oxidation–Reduction Reactions
C. Anaerobic Glycolysis
VI. Oxygenases and Oxidases Not Involved in ATP Generation
A. Oxidases
B. Oxygenases
VII. Energy Balance
Chapter 20: Review Questions
21 Digestion, Absorption, and Transport of Carbohydrates
I. Dietary Carbohydrates
II. Digestion of Dietary Carbohydrates
A. Salivary and Pancreatic α-Amylase
B. Disaccharidases of the Intestinal Brush-Border Membrane
C. Metabolism of Sugars by Colonic Bacteria
D. Lactose Intolerance
III. Dietary Fiber
IV. Absorption of Sugars
A. Absorption by the Intestinal Epithelium
B. Transport of Monosaccharides into Tissues
V. Glucose Transport through the Blood–Brain Barrier and into Neurons
Chapter 21: Review Questions
22 Generation of Adenosine Triphosphate from Glucose, Fructose, and Galactose: Glycolysis
I. Glycolysis
A. The Reactions of Glycolysis
B. Fructose
C. Galactose Metabolism; Conversion to Glucose 1-Phosphate
D. Oxidative Fates of Pyruvate and NADH
E. Anaerobic Glycolysis
II. Other Functions of Glycolysis
III. Regulation of Glycolysis by the Need for ATP
A. Relationships among ATP, ADP, and AMP Concentrations
B. Regulation of Hexokinases
C. Regulation of PFK-1
D. Regulation of Pyruvate Kinase
IV. Lactic Acidemia
Chapter 22: Review Questions
23 Tricarboxylic Acid Cycle
I. Overview of the Tricarboxylic Acid Cycle
II. Reactions of the Tricarboxylic Acid Cycle
A. Formation and Oxidation of Isocitrate
B. α-Ketoglutarate to Succinyl Coenzyme A
C. Generation of Guanosine Triphosphate
D. Oxidation of Succinate to Oxaloacetate
III. Coenzymes of the Tricarboxylic Acid Cycle
A. Flavin Adenine Dinucleotide and NAD+
B. Role of Coenzyme A in the Tricarboxylic Acid Cycle
C. The α-Keto Acid Dehydrogenase Complexes
IV. Energetics of the Tricarboxylic Acid cycle
A. Overall Efficiency of the Tricarboxylic Acid Cycle
B. Thermodynamically and Kinetically Reversible and Irreversible Reactions
V. Regulation of the Tricarboxylic Acid Cycle
A. Regulation of Citrate Synthase
B. Allosteric Regulation of Isocitrate Dehydrogenase
C. Regulation of α-Ketoglutarate Dehydrogenase
D. Regulation of Tricarboxylic Acid Cycle Intermediates
VI. Precursors of Acetyl Coenzyme A
A. Sources of Acetyl Coenzyme A
B. Pyruvate Dehydrogenase Complex
VII. Tricarboxylic Acid Cycle Intermediates and Anaplerotic Reactions
A. Tricarboxylic Acid Cycle Intermediates Are Precursors for Biosynthetic Pathways
B. Anaplerotic Reactions
Chapter 23: Review Questions
24 Oxidative Phosphorylation and Mitochondrial Function
I. Oxidative Phosphorylation
A. Overview of Oxidative Phosphorylation
B. Oxidation–Reduction Components of the Electron Transport Chain
C. Pumping of Protons
D. Energy Yield from the Electron Transport Chain
E. Cytoplasmic NADH
F. Respiratory Chain Inhibition and Sequential Transfer
II. OXPHOS Diseases
A. Mitochondrial DNA and OXPHOS Diseases
B. Other Genetic Disorders of Oxidative Phosphorylation
C. Lactic Acidosis
III. Coupling of Electron Transport and ATP Synthesis
A. Regulation through Coupling
B. Uncoupling ATP Synthesis from Electron Transport
IV. Transport through Inner and Outer Mitochondrial Membranes
A. Transport through the Inner Mitochondrial Membrane
B. Transport through the Outer Mitochondrial Membrane
C. The Mitochondrial Permeability Transition Pore
Chapter 24: Review Questions
25 Oxygen Toxicity and Free-Radical Injury
I. O2 and the Generation of Reactive Oxygen Species
A. The Radical Nature of O2
B. Characteristics of Reactive Oxygen Species
C. Major Sources of Primary Reactive Oxygen Species in the Cell
II. Oxygen Radical Reactions with Cellular Components
A. Membrane Attack: Formation of Lipid and Lipid Peroxy Radicals
B. Proteins and Peptides
C. DNA
III. Nitric Oxide and Reactive Nitrogen–Oxygen Species
A. Nitric Oxide Synthase
B. NO Toxicity
IV. Formation of Free Radicals during Phagocytosis and Inflammation
A. NADPH Oxidase
B. Myeloperoxidase and HOCl
C. RNOS and Inflammation
V. Cellular Defenses against Oxygen Toxicity
A. Antioxidant Scavenging Enzymes
B. Nonenzymatic Antioxidants (Free-Radical Scavengers)
Chapter 25: Review Questions
26 Formation and Degradation of Glycogen
I. Structure of Glycogen
II. Function of Glycogen in Skeletal Muscle and Liver
III. Synthesis and Degradation of Glycogen
A. Glycogen Synthesis
B. Glycogen Degradation
IV. Disorders of Glycogen Metabolism
V. Regulation of Glycogen Synthesis and Degradation
A. Regulation of Glycogen Metabolism in Liver
B. Regulation of Glycogen Synthesis and Degradation in Skeletal Muscle
Chapter 26: Review Questions
27 Pentose Phosphate Pathway and the Synthesis of Glycosides, Lactose, Glycoproteins, and Glycolipids
I. The Pentose Phosphate Pathway
A. Oxidative Phase of the Pentose Phosphate Pathway
B. Nonoxidative Phase of the Pentose Phosphate Pathway
C. Role of the Pentose Phosphate Pathway in Generation of NADPH
II. Interconversions Involving Nucleotide Sugars
A. Reactions of UDP-Glucose
B. UDP-Glucuronate: A Source of Negative Charges
C. Glucuronides: A Source of Negative Charges
D. Synthesis of UDP-Galactose and Lactose from Glucose
E. Formation of Sugars for Glycolipid and Glycoprotein Synthesis
III. Glycoproteins
A. Structure and Function
B. Synthesis
IV. Glycolipids
A. Function and Structure
B. Synthesis
Chapter 27: Review Questions
28 Gluconeogenesis and Maintenance of Blood Glucose Levels
I. Glucose Metabolism in the Liver
II. Gluconeogenesis
A. Precursors for Gluconeogenesis
B. Formation of Gluconeogenic Intermediates from Carbon Sources
C. Pathway of Gluconeogenesis
D. Regulation of Gluconeogenesis
E. Energy Is Required for the Synthesis of Glucose
III. Changes in Blood Glucose Levels after a Meal
A. Blood Glucose Levels in the Fed State
B. Blood Glucose Levels in the Fasting State
C. Blood Glucose Levels during Prolonged Fasting (Starvation)
D. Summary of Sources of Blood Glucose
E. Blood Glucose Levels during Exercise
Chapter 28: Review Questions
Section V: Lipid Metabolism
29 Digestion and Transport of Dietary Lipids
I. Digestion of Triacylglycerols
A. Action of Bile Salts
B. Action of Pancreatic Lipase
II. Absorption of Dietary Lipids
III. Synthesis of Chylomicrons
IV. Transport of Dietary Lipids in the Blood
V. Fate of Chylomicrons
Chapter 29: Review Questions
30 Oxidation of Fatty Acids and Ketone Bodies
I. Fatty Acids as Fuels
A. Characteristics of Fatty Acids Used as Fuels
B. Transport and Activation of Long-Chain Fatty Acids
C. β-Oxidation of Long-Chain Fatty Acids
D. Oxidation of Medium-Chain-Length Fatty Acids
E. Regulation of -Oxidation
II. Alternative Routes of Fatty Acid Oxidation
A. Peroxisomal Oxidation of Fatty Acids
B. β-Oxidation of Fatty Acids
III. Metabolism of Ketone Bodies
A. Synthesis of Ketone Bodies
B. Oxidation of Ketone Bodies as Fuels
C. Alternative Pathways of Ketone Body Metabolism
IV. The Role of Fatty Acids and Ketone Bodies in Fuel Homeostasis
A. Preferential Utilization of Fatty Acids
B. Tissues That Use Ketone Bodies
C. Regulation of Ketone Body Synthesis
Chapter 30: Review Questions
31 Synthesis of Fatty Acids, Triacylglycerols, and the Major Membrane Lipids
I. Fatty Acid Synthesis
A. Conversion of Glucose to Cytosolic Acetyl Coenzyme A
B. Conversion of Acetyl CoA to Malonyl CoA
C. Fatty Acid Synthase Complex
D. Elongation of Fatty Acids
E. Desaturation of Fatty Acids
II. Synthesis of the Eicosanoids
A. Source of the Eicosanoids
B. Pathways for Eicosanoid Synthesis
Eicosanoids
I. Lipoxygenase Pathway: Synthesis of the Leukotrienes, HETE, and Lipoxins
A. Leukotriene Synthesis
B. Lipoxin Synthesis and Actions
II. Cytochrome P450 Pathway: Synthesis and Actions of Epoxides, HETEs, and diHETEs
III. Isoprostane Synthesis
IV. Endocannabinoid Synthesis
V. The Inflammatory Process
C. Cyclooxygenase Pathway: Synthesis of the Prostaglandins and Thromboxanes
D. Mechanism of Action of the Eicosanoids
III. Synthesis of Triacylglycerols and VLDL Particles
IV. Fate of the VLDL Triglyceride
V. Storage of Triacylglycerols in Adipose Tissue
VI. Release of Fatty Acids from Adipose Triacylglycerols
Glyceroneogenesis
Regulation of Fatty Acid Release by Glyceroneogenesis
VII. Metabolism of Glycerophospholipids and Sphingolipids
A. Synthesis of Phospholipids Containing Glycerol
B. Degradation of Glycerophospholipids
C. Sphingolipids
VIII. The Adipocyte as an Endocrine Organ
A. Leptin
B. Adiponectin
Chapter 31: Review Questions
32 Cholesterol Absorption, Synthesis, Metabolism, and Fate
I. Intestinal Absorption of Cholesterol
II. Cholesterol Synthesis
A. Stage 1: Synthesis of Mevalonate from Acetyl CoA
B. Stage 2: Conversion of Mevalonate to Two Activated Isoprenes
C. Stage 3: Condensation of Six Activated 5-Carbon Isoprenes to Squalene
D. Stage 4: Conversion of Squalene to the Steroid Nucleus
E. Regulation of HMG-CoA Reductase
III. Several Fates of Cholesterol
IV. Synthesis of Bile Salts
A. Conversion of Cholesterol to Cholic Acid and Chenodeoxycholic Acid
B. Conjugation of Bile Salts
C. Fate of the Bile Salts
V. Transport of Cholesterol by the Blood Lipoproteins
A. Chylomicrons
B. Very-Low-Density Lipoprotein
C. Intermediate-Density Lipoprotein and Low-Density Lipoprotein
D. High-Density Lipoprotein
VI. Receptor-Mediated Endocytosis of Lipoproteins
VII. Lipoprotein Receptors
A. The LDL Receptor
B. LDL Receptor-Related Protein-1
C. Macrophage Scavenger Receptor
VIII. Anatomic and Biochemical Aspects of Atherosclerosis
IX. Steroid Hormones
A. Overview of Steroid Hormone Synthesis
B. Synthesis of Cortisol
C. Synthesis of Aldosterone
D. Synthesis of the Adrenal Androgens
E. Synthesis of Testosterone
F. Synthesis of Estrogens and Progesterone
G. Vitamin D Synthesis
Chapter 32: Review Questions
33 Metabolism of Ethanol
I. Ethanol Metabolism
A. Alcohol Dehydrogenase
B. Acetaldehyde Dehydrogenases
C. Fate of Acetate
D. The Microsomal Ethanol-Oxidizing System
E. Variations in the Pattern of Ethanol Metabolism
F. The Energy Yield of Ethanol Oxidation
II. Toxic Effects of Ethanol Metabolism
A. Acute Effects of Ethanol Arising from the Increased NADH/NAD+ Ratio
B. Acetaldehyde Toxicity
C. Ethanol and Free-Radical Formation
D. Hepatic Cirrhosis and Loss of Liver Function
Chapter 33: Review Questions
34 Integration of Carbohydrate and Lipid Metabolism
I. Regulation of Carbohydrate and Lipid Metabolism in the Fed State
A. Mechanisms That Affect Glycogen and Triacylglycerol Synthesis in Liver
B. Mechanisms That Affect the Fate of Chylomicrons and VLDL
C. Mechanisms That Affect Triacylglycerol Storage in Adipose Tissue
II. Regulation of Carbohydrate and Lipid Metabolism during Fasting
A. Mechanisms in Liver That Serve to Maintain Blood Glucose Levels
B. Mechanisms That Affect Lipolysis in Adipose Tissue
C. Mechanisms That Affect Ketone Body Production by the Liver
D. Regulation of the Use of Glucose and Fatty Acids by Muscle
III. The Importance of AMP and Fructose 2,6-Bisphosphate
IV. General Summary
Chapter 34: Review Questions
Section VI: Nitrogen Metabolism
35 Protein Digestion and Amino Acid Absorption
I. Protein Digestion
A. Digestion in the Stomach
B. Digestion by Enzymes from the Pancreas
C. Digestion by Enzymes from Intestinal Cells
II. Absorption of Amino Acids
A. Cotransport of Sodium Ions and Amino Acids
B. Transport of Amino Acids into Cells
III. Protein Turnover and Replenishment of the Intracellular Amino Acid Pool
A. Lysosomal Protein Turnover
B. The Ubiquitin–Proteasome Pathway
Chapter 35: Review Questions
36 Fate of Amino Acid Nitrogen: Urea Cycle
I. Fate of Amino Acid Nitrogen
A. Transamination Reactions
B. Removal of Amino Acid Nitrogen as Ammonia
C. Role of Glutamate in the Metabolism of Amino Acid Nitrogen
D. Role of Alanine and Glutamine in Transporting Amino Acid Nitrogen to the Liver
II. Urea Cycle
A. Reactions of the Urea Cycle
B. Origin of Ornithine
C. Regulation of the Urea Cycle
D. Function of the Urea Cycle during Fasting
E. Disorders of the Urea Cycle
Chapter 36: Review Questions
37 Synthesis and Degradation of Amino Acids
I. The Role of Cofactors in Amino Acid Metabolism
II. Amino Acids Derived from Intermediates of Glycolysis
A. Serine
B. Glycine
C. Cysteine
D. Alanine
III. Amino Acids Related to TCA Cycle Intermediates
A. Amino Acids Related through α-Ketoglutarate/Glutamate
B. Amino Acids Related to Oxaloacetate (Aspartate and Asparagine)
C. Amino Acids That Form Fumarate
D. Amino Acids That Form Succinyl CoA
IV. Amino Acids That Form Acetyl CoA and Acetoacetate
A. Phenylalanine and Tyrosine
B. Tryptophan
C. Threonine, Isoleucine, Leucine, and Lysine
Chapter 37: Review Questions
38 Tetrahydrofolate, Vitamin B12, and S-Adenosylmethionine
I. Tetrahydrofolate (FH4)
A. Structure and Forms of FH4
B. The Vitamin Folate
C. Oxidation and Reduction of the One-Carbon Groups of Tetrahydrofolate
D. Sources of One-Carbon Groups Carried by FH4
E. Recipients of One-Carbon Groups
II. Vitamin B12
III. S-Adenosylmethionine
IV. Relationships among Folate, Vitamin B12, and SAM
A. The Methyl-Trap Hypothesis
B. Hyperhomocysteinemia
C. Neural Tube Defects
D. Folate Deficiencies and DNA Synthesis
V. Choline and One-Carbon Metabolism
Chapter 38: Review Questions
39 Purine and Pyrimidine Metabolism
I. Purines and Pyrimidines
II. Purine Biosynthesis
A. De Novo Synthesis of the Purine Nucleotides
B. Purine Salvage Pathways
III. Synthesis of the Pyrimidine Nucleotides
A. De Novo Pathways
B. Salvage of Pyrimidine Bases
C. Regulation of De Novo Pyrimidine Synthesis
IV. The Production of Deoxyribonucleotides
V. Degradation of Purine and Pyrimidine Bases
A. Purine Bases
B. Pyrimidine Bases
Chapter 39: Review Questions
40 Intertissue Relationships in the Metabolism of Amino Acids
I. Maintenance of the Free Amino Acid Pool in Blood
A. Interorgan Flux of Amino Acids in the Postabsorptive State
B. Principles Governing Amino Acid Flux between Tissues
II. Utilization of Amino Acids in Individual Tissues
A. The Kidney
B. Skeletal Muscle
D. The Liver
E. Brain and Nervous Tissue
III. Changes in Amino Acid Metabolism with Dietary and Physiological State
A. High-Protein Meal
B. Hypercatabolic States
Chapter 40: Review Questions
Section VII: Tissue Metabolism
41 Actions of Hormones That Regulate Fuel Metabolism
I. Physiologic Effects of Insulin and Amylin
II. Physiologic Effects of Glucagon
III. Physiologic Effects of Other Counterregulatory Hormones
A. Somatostatin
B. Growth Hormone
C. Catecholamines (Epinephrine, Norepinephrine, Dopamine)
D. Glucocorticoids
E. Thyroid Hormone
F. Gastrointestinal-Derived Hormones That Affect Fuel Metabolism
G. Neural Factors That Control Secretion of Insulin and Counterregulatory Hormones
The Endocannabinoid System and Energy Homeostasis
Chapter 41: Review Questions
42 The Biochemistry of Erythrocytes and Other Blood Cells
I. Cells of the Blood
A. Classification and Functions of Leukocytes and Thrombocytes
B. Anemia
II. Erythrocyte Metabolism
A. The Mature Erythrocyte
B. The Erythrocyte Precursor Cells and Heme Synthesis
III. The Red Blood Cell Membrane
IV. Hematopoiesis
A. Cytokines and Hematopoiesis
B. Erythropoiesis
C. Nutritional Anemias
V. Hemoglobinopathies, Hereditary Persistence of Fetal Hemoglobin, and Hemoglobin Switching
A. Hemoglobinopathies: Disorders in the Structure or Amount of the Globin Chains
B. Thalassemias
C. Hereditary Persistence of Fetal Hemoglobin
D. Hemoglobin Switching: A Developmental Process Controlled by Transcription Factors
E. Structure and Transcriptional Regulation of the α- and β-Globin Gene Loci
Chapter 42: Review Questions
43 Blood Plasma Proteins, Coagulation, and Fibrinolysis
I. Plasma Proteins Maintain Proper Distribution of Water between Blood and Tissues
A. Body Fluid Maintenance between Tissues and Blood
B. The Major Serum Protein, Albumin
II. The Plasma Contains Proteins That Aid in Immune Defense
III. Plasma Proteins Maintain the Integrity of the Circulatory System
A. Formation of the Hemostatic Plug
B. The Blood Coagulation Cascade
C. The Process of Blood Coagulation
D. Regulation through Feedback Amplification and Inhibition
E. Thromboresistance of Vascular Endothelium
F. Fibrinolysis
G. Regulation of Fibrinolysis
Chapter 43: Review Questions
44 Liver Metabolism
I. Liver Anatomy
II. Liver Cell Types
A. Hepatocytes
B. Endothelial Cells
C. Kupffer Cells
D. Hepatic Stellate Cells
E. Pit Cells
III. Major Functions of the Liver
A. The Liver Is a Central Receiving and Recycling Center for the Body
B. Inactivation and Detoxification of Xenobiotic Compounds and Metabolites
C. Regulation of Blood Glucose Levels
D. Synthesis and Export of Cholesterol and Triacylglycerol
E. Ammonia and the Urea Cycle
F. Formation of Ketone Bodies
G. Nucleotide Biosynthesis
H. Synthesis of Blood Proteins
I. The Synthesis of Glycoproteins and Proteoglycans
J. The Pentose Phosphate Pathway
IV. Fuels for the Liver
A. Carbohydrate Metabolism in the Liver
B. Glucose as a Fuel
C. Lipid Metabolism
D. Amino Acid Metabolism in the Liver
E. Amino Acid Metabolism in Liver Disease
V. Diseases of the Liver
Chapter 44: Review Questions
45 Metabolism of Muscle at Rest and during Exercise
I. Muscle Cell Types
A. Skeletal Muscle
B. Smooth Muscle Cells
C. Cardiac Muscle Cells
II. Neuronal Signals to Muscle
III. Glycolysis and Fatty Acid Metabolism in Muscle Cells
IV. Fuel Utilization in Cardiac Muscle
A. Normal Conditions
B. Ischemic Conditions
V. Fuel Utilization in Skeletal Muscle
A. ATP and Creatine Phosphate
B. Fuel Use at Rest
C. Fuel Use during Starvation
D. Fuel Utilization during Exercise
VI. Mild and Moderate-Intensity Long-Term Exercise
A. Lactate Release Decreases with Duration of Exercise
B. Blood Glucose as a Fuel
C. Free Fatty Acids as a Source of ATP
D. Branched-Chain Amino Acids
E. The Purine Nucleotide Cycle
F. Acetate
VII. Metabolic Effects of Training on Muscle Metabolism
Chapter 45: Review Questions
46 Metabolism of the Nervous System
I. Cell Types of the Nervous System
A. Neurons
B. Neuroglial Cells
II. THE BLOOD–BRAIN BARRIER
A. Capillary Structure
B. Transport through the Blood–Brain Barrier
III. SYNTHESIS OF SMALL NITROGEN-CONTAINING NEUROTRANSMITTERS
A. General Features of Neurotransmitter Synthesis
B. Dopamine, Norepinephrine, and Epinephrine
C. Metabolism of Serotonin
D. Metabolism of Histamine
E. Acetylcholine
F. Glutamate and GABA
G. Other Amino Acid Neurotransmitters
IV. METABOLIC ENCEPHALOPATHIES AND NEUROPATHIES
A. Hypoglycemic Encephalopathy
B. Hypoxic Encephalopathy
C. Relationship between Glutamate Synthesis and the Anaplerotic Pathways of Pyruvate Carboxylase and Methylmalonyl CoA Mutase
V. LIPID SYNTHESIS IN THE BRAIN AND PERIPHERAL NERVOUS SYSTEM
A. Brain Lipid Synthesis and Oxidation
B. Myelin Synthesis
Chapter 46: Review Questions
47 The Extracellular Matrix and Connective Tissue
I. Composition of the Extracellular Matrix
A. Fibrous Proteins
B. Proteoglycans
II. Integrins
III. Adhesion Proteins
IV. Matrix Metalloproteinases
Chapter 47: Review Questions
Patient Index
Subject Index