Netter biochemistry

Front Cover
Inside Front Cover
Marketing page
Netter's Essential Biochemistry
Copyright Page
Dedication
About the Author
Acknowledgments
Coauthors and Chapter Reviewers
About the Artist
Frank H. Netter, MD
Preface
Table Of Contents
1 Human Karyotype and the Structure of DNA
Learning Objectives
Synopsis
1. Chemical Structure of DNA
2. Hydrogen Bonding Between Complementary Bases
3. DNA Double Helix
4. Packing of DNA Double Helices Into Chromatids
5. Changes in DNA Topology
6. Human Karyotype
Summary
Further Reading
Review Questions
2 DNA Repair and Therapy of Cancer
Learning Objectives
Synopsis
1. Base-Excision Repair
2. Mismatch Repair
3. Nucleotide-Excision Repair
4. Repair of Double-Strand Breaks and Interstrand Crosslinks
4.1. Nonhomologous End Joining
4.2. Homologous Recombination Repair (Homology-Directed Repair)
5. DNA Damage Response Halts the Cell Cycle and Regulates Apoptosis
Summary
Further Reading
Review Questions
3 DNA Replication
Learning Objectives
Synopsis
1. DNA Replication
2. Translesion Dna Synthesis
3. Replication of the Ends of Chromosomes (Telomeres)
Summary
Further Reading
Review Questions
4 Clinical Tests Based on DNA or RNA
Learning Objectives
Synopsis
1. Conventional Cytogenetics and Fluorescence in Situ Hybridization
2. DNA Amplification by Polymerase Chain Reaction
3. Electrophoresis and Melting Curve Analysis of DNA
4. DNA Microarray–Based Technologies
5. DNA Sequencing
5.1. Sanger Sequencing
5.2. Massive Parallel Sequencing
6. Selected Clinical Applications of DNA-Based Testing
6.1. Prenatal Diagnosis
6.2. Other Common Nucleic Acid–Based Tests
Summary
Further Reading
Review Questions
5 Basic Genetics for Biochemistry
Learning Objectives
Synopsis
1. Chromosomes and Alleles
2. Imprinting and Patterns of Inheritance
3. Mutations and Markers
Summary
Review Question
6 Transcription and RNA Processing
Learning Objectives
Synopsis
1. DNA Methylation and Packing Impede Transcription
2. The Process of Transcription
3. Processing of RNA During and After Transcription
3.1. Capping of Pre-mRNA
3.2. Polyadenylation of Pre-mRNA
3.3. Splicing of Pre-mRNA
3.4. Alternative Splicing of Pre-mRNA
3.5. Export of mRNA Into the Cytosol
3.6. Degradation of mRNA
Summary
Further Reading
Review Questions
7 Translation and Posttranslational Protein Processing
Learning Objectives
Synopsis
1. Codons and the Genetic Code
2. Transfer RNAs
3. Ribosomes Translate mRNA Into Protein
4. Posttranslational Modification
4.1. General Comments
4.2. Glycosylation
4.3. Acylation With Fatty Acids and Prenylation
4.4. Phosphorylation, Sulfation, and Nitrosylation
4.5. Ubiquitylation and SUMOylation
5. Protein Sorting and Quality Control
Summary
Further Reading
Review Questions
8 Cell Cycle and Cancer
Learning Objectives
Synopsis
1. Cell Cycle and Its Regulation
1.1. Cell Cycle and the Retinoblastoma Pathway
1.2. The p53 Tumor Suppressor Pathway
1.3. The WNT/β-Catenin Pathway
1.4. Role of MYCs
1.5. Apoptosis
1.6. Control of S, G2, and M Phases of the Cell Cycle
2. Genetic Alterations in Cancer Cells
2.1. Genetic Alterations That Favor Neoplasia
2.2. Effect of Age on Tumorigenesis
2.3. Smoking and Cancer
2.4. Obesity, Alcohol, and Cancer
2.5. Circulating Tumor Cells
3. Examples of Common Neoplasms
3.1. Breast Cancer
3.2. Lung Cancer
3.3. Prostate Cancer
3.4. Colorectal Cancer
3.5. Melanoma
4. Glucose Use by Tumors
Summary
Further Reading
Review Questions
9 Structure of Proteins and Protein Aggregates in Degenerative Diseases
Learning Objectives
Synopsis
1. Amino Acids as Building Blocks of Peptides and Proteins
1.1. General Comments About Amino Acids
1.2. Classification of Amino Acids
2. Peptide Bonds, Disulfide Bridges, and Crosslinks
2.1. Peptide Bonds
2.2. Disulfide Bridges and Other Crosslinks
3. Forces That Determine the Conformation of Proteins and Peptides
3.1. Hydrophobic Effects
3.2. Hydrogen Bonds
3.3. Electrostatic Interactions
3.4. Van der Waals Interactions
3.5. Coordination of Metal Ions
3.6. Entropy
4. Elements of the Three-Dimensional Protein Structure
4.1. α-Helix
4.2. β-Sheets
4.3. Loops
4.4. Motifs and Domains
4.5. Primary, Secondary, Tertiary, and Quaternary Protein Structure
5. Unstructured Proteins
6. Protein Folding
7. Denaturation of Proteins
8. Diseases That Are Accompanied by Excessive Protein Aggregation
8.1. Formation of Extracellular Amyloid Fibrils
8.2. Formation of Intracellular Aggregates
8.3. Alzheimer Disease
8.4. Type 2 Diabetes
8.5. Parkinson Disease
Summary
Further Reading
Review Questions
10 Enzymes and Consequences of Enzyme Deficiencies
Learning Objectives
Synopsis
1. Nomenclature of Enzymes
2. Enzyme Catalysis of Chemical Reactions
3. Enzyme Activity as A Function of the Concentration of Substrates
4. Activators and Inhibitors of Enzymes
5. Enzyme Activity and Flux in Metabolic Pathways
6. Enzymes in the Blood That Have Diagnostic Significance
7. Enzyme-Linked Immunosorbent Assay
Summary
Further Reading
Review Questions
11 Biological Membranes
Learning Objectives
Synopsis
1. Structure and Composition of Membranes
1.1. Physiological Roles of Membranes
1.2. Structure of Lipids
1.3. Composition and Structure of Bilayer Membranes
1.4. Transport of Lipids Inside Membranes
1.5. Membrane Proteins
2. Movement of Molecules Across Membranes
2.1. Simple Diffusion of Molecules Through the Hydrophobic Core of the Lipid Bilayer
2.2. Transport of Molecules Through Transport Proteins in Membranes
Summary
Further Reading
Review Questions
12 Collagen, Collagenopathies, and Diseases of Mineralization
Learning Objectives
Synopsis
1. Biosynthesis and Degradation of Fibrillar Collagens
1.1. Overview of Types of Collagen
1.2. Biosynthesis and Posttranslational Modification of Fibrillar Collagens
1.3. Mineralization of Fibrillar Collagens in Bone
1.4. Degradation of Fibrillar Collagens
2. Diseases of Bone That Are Associated With Fibrillar Collagens
2.1. Overview and General Comments
2.2. Hypochondroplasia and Achondroplasia
2.3. Vitamin C (Ascorbate) Deficiency
2.4. Osteogenesis Imperfecta
2.5. Ehlers-Danlos Syndrome
2.6. Rickets and Osteomalacia
2.7. Paget Disease of Bone (Osteitis Deformans)
2.8. Osteoporosis
3. Type IV Collagen: a Network-Forming Collagen
4. Type VII Collagen: the Collagen of Anchoring Fibrils
Summary
Further Reading
Review Questions
13 Pathologic Alterations of the Extracellular Matrix That Involve Fibrillin, Elastin, or Proteoglycans
Learning Objectives
Synopsis
1. Elastin and Fibrillins
1.1. Synthesis of Elastic Fibers
1.2. Marfan Syndrome
1.3. Supravalvular Aortic Stenosis
1.4. Degradation of Elastic Fibers, Emphysema, and α-1-Antitrypsin Deficiency
2. Proteoglycans and Glycosaminoglycans
2.1. Synthesis and Degradation of Proteoglycans Containing Heparan, Keratan, Chondroitin, or Dermatan Sulfate
2.2. Hyaluronate, a Glycosaminoglycan That Binds to Link Proteins
2.3. Osteoarthritis
2.4. Mucopolysaccharidoses
3. Remodeling of the Extracellular Matrix
3.1. Wound Healing
3.2. Remodeling of the Cervix
3.3. Fibrosis
Summary
Further Reading
Review Questions
14 Heme Metabolism, Porphyrias, and Hyperbilirubinemia
Learning Objectives
Synopsis
1. Heme Synthesis
1.1. Use of Heme in Proteins
1.2. Pathway and Regulation of Heme Synthesis
2. Diseases Associated With Heme Synthesis
2.1. General Considerations
2.2. Use of Porphyrins for Photodiagnostic Purposes and Photodynamic Therapy
2.3. Diseases of Heme Synthesis That Primarily Affect the Nervous System
2.3.1. Acute Intermittent Porphyria
2.3.2. Lead Poisoning and ALA Dehydratase-Deficient Porphyria
2.4. Diseases of Heme Synthesis That Affect Only the Skin
2.4.1. Porphyria Cutanea Tarda
2.4.2. Other Porphyrias That Affect the Skin but Not the Nervous System
2.5. Porphyrias That Affects Both the Nervous System and the Skin
2.6. Diseases of Heme Synthesis That Cause Anemia but Not Neurotoxicity or Skin Damage
3. Degradation of Heme to Bilirubin
4. Lab Assays: Direct, Total, and Indirect Bilirubin
5. Problems With the Degradation of Heme
5.1. General Considerations
5.2. Hyperbilirubinemia Due to Impaired Excretion of Conjugated Bilirubin
5.2.1. Acquired Cholestasis
5.2.2. Congenital Impairment of Hepatic Bilirubin Diglucuronide Secretion: Dubin-Johnson Syndrome
5.3. Hyperbilirubinemia Due to Increased Degradation of Heme
5.4. Hyperbilirubinemia Due to Inadequate Conjugation of Bilirubin
5.4.1. Neonatal Jaundice
5.4.2. Crigler-Najjar Syndrome
5.4.3. Gilbert Syndrome
5.4.4. Acquired Deficiency of Bilirubin Conjugation
Summary
Further Reading
Review Questions
15 Iron Metabolism
Learning Objectives
Synopsis
1. The Body’s Principal Iron Stores
2. Absorption of Dietary Iron
3. Regulation of Iron Release Into the Bloodstream
4. Transport of Iron in the Blood
5. Iron in Mitochondria
6. Daily Flow of Iron
7. Interpretation of Laboratory Data Related to Iron
8. Iron Deficiency
8.1. Iron-Deficiency Anemia
8.2. Anemia of Inflammation
9. Iron Overload
9.1. General Comments on Iron Overload
9.2. Hemochromatosis
9.3. Iron Overload With Blood Transfusions
9.4. Iron Chelation Therapy
9.5. Hemosiderosis and Siderosis
9.6. Acute Iron Poisoning
Summary
Further Reading
Review Questions
16 Erythropoiesis, Hemoglobin Function, and the Complete Blood Count
Learning Objectives
Synopsis
1. Erythropoiesis
1.1. Location of Erythropoiesis
1.2. Major Stages in Erythropoiesis
1.3. Role of Erythropoietin in the Control of Red Blood Cell Production
1.4. Oxygen-Dependent Secretion of Erythropoietin
1.5. Clinical Uses of Recombinant Erythropoietin
2. Protein Composition of Hemoglobin
3. Oxygen Binding by Hemoglobin and Myoglobin
3.1. Cooperative Binding of O2 to Hemoglobin
3.2. Short-Term Regulation of the O2 Affinity of Hemoglobin
3.3. Long-Term Regulation of the O2 Affinity of Hemoglobin
3.4. Maternal-Fetal Exchange of O2
3.5. Binding of O2 to Myoglobin
4. Transport and Buffering Function of CO2 and HCO3− in Blood
5. Carbon Monoxyhemoglobin and Methemoglobin
5.1. Carbon Monoxyhemoglobin
5.2. Oxidation of Hemoglobin to Methemoglobin
6. Clinically Important Laboratory Data on Red Blood Cells
7. Color of Hemoglobins
7.1. Effect of Hemoglobin on Skin Color
7.2. Pulse Oximeter
Summary
Further Reading
Review Questions
17 Hemoglobinopathies
Learning Objectives
Synopsis
1. Link Between Malaria and Some Hemoglobinopathies
2. Thalassemias
2.1. General Comments About the Thalassemias
2.2. α-Thalassemia Trait, Hemoglobin H Disease, and Hemoglobin Barts Hydrops Fetalis Syndrome
2.3. β-Thalassemia
3. Sickle Cell Anemia and Hemoglobin S
3.1. Cause and the Genetics of Sickle Cell Anemia
3.2. Polymerization of Deoxyhemoglobin S
3.3. Vaso-Occlusive Episodes in Sickle Cell Anemia
4. Hemoglobin C, Hemoglobin SC, and Hemoglobin E Disease
5. Summary of the Causes and Manifestations of the Most Common Hemoglobinopathies
6. Hemoglobin Analysis for the Diagnosis of Hemoglobin Disorders
Summary
Further Reading
Review Questions
18 Carbohydrate Transport, Carbohydrate Malabsorption, and Lactose Intolerance
Learning Objectives
Synopsis
1. Classification of Carbohydrates
2. Digestion of Polysaccharides and Disaccharides in the Small Intestine
2.1. Structure of the Small Intestine
2.2. Hydrolysis of Polysaccharides and Disaccharides to Monosaccharides
3. Transport of Monosaccharides
3.1. Intestinal Monosaccharide Transport
3.2. Monosaccharide Transport in Tissues Other Than the Intestine
4. Bacterial Metabolism of Undigested Carbohydrates That Reach the Colon
5. Carbohydrate Malabsorption
5.1. General Comments
5.2. Pancreatic Insufficiency
5.3. Diminished Capacity of the Small Intestine to Degrade Carbohydrates
6. SGLT Inhibitors: Drugs That Inhibit Na+-Coupled Glucose Transport
Summary
Further Reading
Review Questions
19 Glycolysis and Its Regulation by Hormones and Hypoxia
Learning Objectives
Synopsis
1. Chemical Reactions of Glycolysis
2. Aerobic Versus Anaerobic Glycolysis
2.1. Production of NADH in Glycolysis
2.2. Cells Performing Anaerobic Glycolysis Release Lactic Acid
2.3. Aerobic Glycolysis: Cells Produce ATP From the Reducing Power of NADH
3. Basic Mechanisms in the Regulation of Glycolysis
3.1. Overview
3.2. Introduction to Insulin, Glucagon, Epinephrine, and Norepinephrine
3.3. Introduction to AMP-Dependent Protein Kinase
3.4. Regulation of Glucose Transport
3.5. Regulation of Hexokinase and Glucokinase Activities
3.6. Regulation of Phosphofructokinase 1
3.7. Regulation of Pyruvate Kinase
3.8. Summary of the Regulation of Flux in Glycolysis
4. Interactions of Glycolysis With Other Pathways
5. Tissue-Specific Regulation of Glycolysis
5.1. Regulation of Glycolysis in Red Blood Cells
5.2. Regulation of Glycolysis in the Brain
5.3. Regulation of Glycolysis in Adipocytes
5.4. Regulation of Glycolysis in Heart Muscle
5.5. Regulation of Glycolysis in Skeletal Muscle
5.6. Regulation of Glycolysis in the Liver
6. Common Laboratory Methods and Assays
6.1. Preservation of Metabolites in Blood Samples
6.2. Plasma or Serum Lactate Dehydrogenase
6.3. 2-Fluoro-Deoxyglucose Positron Emission Tomographic Scans
7. Diseases That Involve an Abnormal Flux in Glycolysis
7.1. Lactate Accumulation
7.2. Effect of Hypophosphatemia on Glycolysis
7.3. Hemolytic Anemias Due to Hereditary Deficiencies of Enzymes of Glycolysis
Summary
Further Reading
Review Questions
20 Fructose and Galactose Metabolism
Learning Objectives
Synopsis
1. Normal Metabolism of Fructose
1.1. Sources of Fructose
1.2. Uptake of Fructose
1.3. Metabolism of Dietary Fructose
2. Polyol Pathway and Its Role in Disease
3. Abnormal Fructose Absorption and Metabolism
3.1. Fructose Malabsorption
3.2. Fructosuria
3.3. Hereditary Fructose Intolerance
3.4. Concerns About High Fructose Consumption in the General Population
3.5. Problems With the Use of Fructose or Sorbitol in Medicine
4. Normal Metabolism of Galactose
5. Galactosemia
5.1. Classical Galactosemia
5.2. Nonclassical Galactosemia
6. Lactose Synthesis in the Lactating Breast
Summary
Further Reading
Review Questions
21 Pentose Phosphate Pathway, Oxidative Stress, and Glucose 6-Phosphate Dehydrogenase Deficiency
Learning Objectives
Synopsis
1. Steps of the Pentose Phosphate Pathway
1.1. General Comments
1.2. Oxidative Branch
1.3. Nonoxidative Branch
1.4. Independent Versus Joint Operation of the Branches
2. Processes That Use NADPH Inside Cells
2.1. Use of NADPH in Biosynthetic Pathways
2.2. NADPH Reduces Oxidized Glutathione
2.3. Removal of ROS and Repair of ROS-Induced Damage
3. Glucose 6-Phosphate Dehydrogenase Deficiency
Summary
Further Reading
Review Questions
22 Citric Acid Cycle and Thiamine Deficiency
Learning Objectives
Synopsis
1. Mitochondria Convert Pyruvate to Acetyl-CoA
2. Reactions of the Citric Acid Cycle
3. Oxaloacetate Helps Replenish Citric Acid Cycle Intermediates
4. Regulation of the Citric Acid Cycle and the Use of Pyruvate
5. Problems Associated With the Citric Acid Cycle
5.1. Inhibition of the Citric Acid Cycle Secondary to Impaired Oxidative Phosphorylation
5.2. Clinically Significant Vitamin Deficiencies
5.2.1. Overview
5.2.2. Deficiency of Thiamine (Vitamin B1)
5.2.3. Deficiency of Riboflavin (Vitamin B2)
5.2.4. Deficiency of Niacin (Vitamin B3, Nicotinic Acid)
5.2.5. Deficiency of Biotin
5.3. Pyruvate Carboxylase Deficiency
5.4. Acute Poisoning With Arsenic
5.5. Tumorigenic Mutations in Isocitrate Dehydrogenase, Succinate Dehydrogenase, or Fumarase
5.6. Deficiency of the Pyruvate Dehydrogenase Complex
Summary
Further Reading
Review Questions
23 Oxidative Phosphorylation and Mitochondrial Diseases
Learning Objectives
Synopsis
1. Oxidative Phosphorylation
1.1. Structure and Function of Mitochondria
1.2. Electron Transport Chain
1.3. Clinically Relevant Inhibitors of the Electron Transport Chain
1.4. ATP Synthase
1.5. Transport of Chemical Energy in the Form of ATP and Phosphocreatine
1.6. Uncouplers of Oxidative Phosphorylation
2. Interplay of Glycolysis, Citric Acid Cycle, and Oxidative Phosphorylation
3. Mitochondrial Dna and Its Inheritance
4. Diseases Involving Mitochondria
4.1. Overview
4.2. Diseases Associated With mtDNA Mutations
4.3. Diseases Associated With Dysfunctional Mitochondria Due to Mutation in the Nucleus
4.4. Idiopathic or Acquired Diseases of Mitochondria
Summary
Further Reading
Review Questions
24 Glycogen Metabolism and Glycogen Storage Diseases
Learning Objectives
Synopsis
1. Synthesis of Glycogen (Glycogenesis)
1.1. Structure and Role of Glycogen
1.2. Reactions of Glycogen Synthesis
1.3. Regulation of Glycogen Synthesis
2. Degradation of Glycogen (Glycogenolysis)
2.1. Degradation of Glycogen to Glucose 6-Phosphate and Glucose
2.2. Regulation of Glycogenolysis
3. Disorders of Glycogen Metabolism
3.1. Diabetes and Glycogen Metabolism
3.2. Fructose and Glycogen Metabolism
3.3. Glycogenoses
Summary
Further Reading
Review Questions
25 Gluconeogenesis and Fasting Hypoglycemia
Learning Objectives
Synopsis
1. Pathway of Gluconeogenesis
2. Substrate and Energy Sources for Gluconeogenesis
2.1. Lactate
2.2. Amino Acids
2.3. Glycerol
2.4. Fatty Acids as a Source of ATP
3. Regulation of Gluconeogenesis
4. Diseases Associated With an Abnormal Rate of Gluconeogenesis
4.1. Diseases Associated With Inadequate Gluconeogenesis
4.1.1. General Comments
4.1.2. Hyperinsulinemia
4.1.3. Hypocortisolism
4.1.4. Liver Disease
4.1.5. Impaired Production of ATP and Intermediates of Gluconeogenesis (Impaired Oxidation of Fatty Acids, Alcohol Intoxication, and Enzyme Deficiencies)
4.2. Diseases Associated With Excessive Gluconeogenesis
4.2.1. General Comments
4.2.2. Insulin Deficiency With Diabetes
4.2.3. Cushing Syndrome
4.2.4. Hyperthyroidism
4.2.5. Pheochromocytoma
4.2.6. Glucagonoma
Summary
Further Reading
Review Questions
26 Insulin and Counterregulatory Hormones
Learning Objectives
Synopsis
1. Structure of the Human Pancreas
2. Synthesis of Glucagon, Glucagon-Like Peptides, Insulin, Epinephrine, and Cortisol
2.1. Synthesis of Glucagon and Glucagon-Like Peptides
2.2. Synthesis of Insulin and Amylin
2.3. Synthesis of Epinephrine and Cortisol in the Adrenal Glands
3. Secretion of Glucagon, Glucagon-Like Peptides, Insulin, Epinephrine, and Cortisol
3.1. Secretion of Glucagon-Like Peptide 1
3.2. Secretion of Glucagon
3.3. Secretion of Insulin
3.3.1. Stimulatory Effect of Glucose
3.3.2. Amplification of Glucose-Induced Insulin Secretion
3.3.3. Inhibition of Insulin Secretion by Catecholamines
3.4. Secretion of Epinephrine and Norepinephrine
3.5. Secretion of Cortisol
4. Effects of Insulin and Counterregulatory Hormones on Tissues
4.1. Biological Effects of Glucagon-Like Peptides
4.2. Biological Effects of Glucagon
4.3. Biological Effects of Insulin
4.4. Biological Effects of Epinephrine and Norepinephrine
4.5. Biological Effects of Cortisol
5. Physiological and Pathological Changes in Insulin Sensing
5.1. General Commen+ts About Insulin Resistance
5.2. Polycystic Ovary Syndrome
6. Pathology of the Secretion of Insulin and Counterregulatory Hormones
6.1. Disorders Associated With Hypoglycemia
6.1.1. Insulinoma
6.1.2. Multiple Endocrine Neoplasia
6.1.3. Congenital Hyperinsulinism
6.1.4. Adrenal Insufficiency
6.2. Disorders Associated With Hyperglycemia
6.2.1. Diabetes Due to Heritable β-Cell Abnormalities
6.2.2. Hyperglycemia Due to Glucagonoma
6.2.3. Hyperglycemia Due to Pheochromocytoma or Cushing Syndrome
Summary
Further Reading
Review Questions
27 Fatty Acids, Ketone Bodies, and Ketoacidosis
Learning Objectives
Synopsis
1. Use and Nomenclature of Fatty Acids
2. Fatty Acid Synthesis
3. Fatty Acid Activation, Elongation, and Desaturation
4. Fatty Acid Oxidation
5. Synthesis and Degradation of Ketone Bodies
5.1. Ketone Body Synthesis (Ketogenesis)
5.2. Oxidation of Ketone Bodies by Extra-Hepatic Tissues
5.3. Laboratory Tests for Ketone Bodies
5.4. Ketosis, Ketonemia, and Ketonuria
6. Overview of Fuel Use by Tissues
7. Metabolic Disturbances of Fatty Acid and Ketone Body Metabolism
7.1. Hypoketotic Hypoglycemia and Disorders of Fatty Acid Oxidation
7.2. Diseases of Very-Long-Chain Fatty Acid Oxidation in Peroxisomes
7.3. Ketoacidosis
Summary
Further Reading
Review Questions
28 Triglycerides and Hypertriglyceridemia
Learning Objectives
Synopsis
1. Structure and Role of Triglycerides
2. Digestion of Triglycerides and Absorption of Fatty Acids and Monoglycerides
2.1. Partial Digestion of Triglycerides in the Stomach
2.2. Digestion of Triglycerides in the Intestine
2.3. Absorption of Fatty Acids and Monoglycerides
3. Production and Export of Triglycerides From the Intestine, Liver, and Mammary Glands
3.1. Triglycerides Made in the Intestine
3.2. Triglycerides Made in the Liver
3.3. Triglycerides Made in the Lactating Mammary Glands
4. Removal of Triglycerides From Chylomicrons and VLDL, and Deposition of Triglycerides Inside Adipocytes
4.1. Removal of Triglycerides From Chylomicrons and VLDL
4.2. Deposition of Triglycerides Inside Adipocytes
5. Hydrolysis of Stored Triglycerides
5.1. Lipolysis
5.2. Hydrolysis of Triglycerides in Muscles
5.3. Daily Course of Triglycerides and Fatty Acids in the Blood
6. Laboratory Determinations
7. Absorption, Transport, and Storage of the Fat-Soluble Vitamins a, D, E, and K
8. Disorders of Triglyceride Metabolism
8.1. Hypertriglyceridemia
8.2. Fatty Liver
8.3. Fat Malabsorption
8.4. Abetalipoproteinemia and Hypobetalipoproteinemia
Summary
Further Reading
Review Questions
29 Cholesterol Metabolism and Hypercholesterolemia
Learning Objectives
Synopsis
1. Absorption of Cholesterol
2. De Novo Synthesis of Cholesterol
2.1. Pathway for the Biosynthesis of Cholesterol
2.2. Regulation of Cholesterol Synthesis
3. Transport of Cholesterol via the Blood
3.1. Transport of Cholesterol From the Liver to Peripheral Cells
3.2. Export of Cholesterol From Peripheral Cells (Reverse Cholesterol Transport)
3.3. Treatment of a Low Concentration of HDL Cholesterol
3.4. Laboratory Measurements of Cholesterol-Containing Lipoproteins
4. Bile Metabolism
4.1. Production of Bile and Recirculation of Bile Salts and Cholesterol
4.2. Diseases of Bile Metabolism
5. Hypercholesterolemia
5.1. Blood Cholesterol Concentration and the Risk of Coronary Artery Disease
5.2. Familial Hypercholesterolemia
5.3. Other Causes of Hypercholesterolemia
5.4. Lowering the Concentration of LDL Cholesterol
6. Combined Hyperlipidemia
6.1. Familial Combined Hyperlipidemia
6.2. Familial Dysbetalipoproteinemia
Summary
Further Reading
Review Questions
30 Metabolism of Ethanol and the Consequences of Alcohol Dependence Syndrome
Learning Objectives
Synopsis
1. Effects of Alcohol Use on the Health of the Public
2. Metabolism of Ethanol
2.1. Metabolism of Ethanol to Acetate
2.2. Oxidation of Acetate to CO2
3. Acute Effect of Ethanol on Pathways of Metabolism
3.1. Effect of Ethanol on Gluconeogenesis
3.2. Effect of Ethanol on Fatty Acid Metabolism
3.3. Effect of Ethanol on the Production of Uric Acid
3.4. Treatment of Acute Ethanol Intoxication in the Clinic
4. Effects of Chronic Ethanol Intake on Organ Function
4.1. General Comments About Alcohol Dependence Syndrome
4.2. Effects of Ethanol and Acetaldehyde on Proteins and DNA
4.3. Drugs That Help Patients Free Themselves From Alcohol Dependence
4.4. Effect of Ethanol on the Liver
4.5. Effect of Ethanol on Cancer Risk
4.6. Effect of Ethanol on the Heart
4.7. Effect of Ethanol on the Fetus
Summary
Further Reading
Review Questions
31 Steroid Hormones and Vitamin D
Learning Objectives
Synopsis
1. General Properties and Synthesis of Steroid Hormones
1.1. Structure and Properties of Steroid Hormones
1.2. Common Pathway of Steroid Hormone Synthesis
2. Sex Steroids
2.1. Common Pathways for the Biosynthesis of Sex Steroids
2.2. Biosynthesis of Sex Steroids in Men
2.3. 46,XY Disorder of Sex Development
2.4. Biosynthesis of Sex Steroids in Women
3. Glucocorticoids
4. Mineralocorticoids
4.1. Synthesis of Aldosterone
4.2. Disorders of Aldosterone Synthesis
5. Vitamin D
Summary
Further Reading
Review Questions
32 Eicosanoids
Learning Objectives
Synopsis
1. Eicosanoid Families
2. Prostaglandins and Thromboxanes
2.1. Synthesis of Prostanoids
2.2. Prostanoid Receptors
2.3. Physiological Roles of Prostaglandins D2, E2, and F2
2.4. Roles of Thromboxane A2 and Prostacyclin
3. Leukotrienes and Lipoxins
3.1. Leukotrienes
3.2. Lipoxins
Summary
Further Reading
Review Questions
33 Signaling
Learning Objectives
Synopsis
1. Principles of Signaling
2. G Protein–Coupled Receptor Signaling
3. Growth Factor Receptors That Are Receptor Tyrosine Kinases
3.1. Normal Receptor Tyrosine Kinase Signaling
3.2. Neurofibromatosis, Noonan Syndrome, and Cowden Syndrome
Summary
Further Reading
Review Questions
34 Digestion of Dietary Protein and Net Synthesis of Protein in the Body
Learning Objectives
Synopsis
1. Digestion of Protein in the Stomach
2. Digestion of Protein in the Intestine
2.1. Normal Protein Digestion in the Intestine
2.2. Diseases Associated With Impaired Digestion of Protein
3. Transport of Amino Acids and Small Peptides
3.1. Normal Transport of Amino Acids in the Intestinal Epithelium and in Other Cells
3.2. Diseases Due to Deficiencies of Amino Acid Transporters
4. Synthesis of Body Protein
4.1. Daily Turnover of Body Protein
4.2. Essential and Nonessential Amino Acids
4.3. Regulation of the Concentration of Amino Acids in Blood and of Protein Synthesis
Summary
Further Reading
Review Questions
35 Protein Degradation, Amino Acid Metabolism, and Nitrogen Balance
Learning Objectives
Synopsis
1. Degradation of Body Protein
1.1. General Comments
1.2. Degradation of Proteins by Proteasomes
1.3. Regulation of Protein Degradation via Proteasomes
1.4. Degradation of Proteins by Lysosomes
2. Elimination of Amino Acid Nitrogen
2.1. Production of Ammonium Ions From Amino Acids
2.2. Excretion of Ammonium Ions Into the Urine
2.3. Transamination
2.4. Role of Glutamine in Nitrogen Metabolism
2.5. Elimination of Nitrogen via the Urea Cycle
3. Deficiencies of Nitrogen Elimination
3.1. General Comments
3.2. Nitrogen Elimination in Patients With Liver Failure or Kidney Failure
3.3. Inborn Deficiencies That Affect the Urea Cycle
4. Summary of the Metabolism of Amino Acids
4.1. Overview
4.2. Normal Metabolism of Phenylalanine, Tyrosine, and Tryptophan
4.3. Hyperphenylalaninemias (Including Phenylketonuria)
4.4. Disorders of Pigmentation
4.5. Disorders of Tyrosine Degradation
4.6. Maple Syrup Disease and the Degradation of Branched-Chain Amino Acids
5. Nitrogen Balance
5.1. Concept of Nitrogen Balance
5.2. Nitrogen Balance in Health and Illness
Summary
Further Reading
Review Questions
36 One-Carbon Metabolism, Folate Deficiency, and Cobalamin Deficiency
Learning Objectives
Synopsis
1. Sources and Absorption of Dietary Folates
1.1. Structure of Folates
1.2. Absorption of Folates in the Intestine and Transport in the Blood
2. Loading Tetrahydrofolates With One-Carbon Groups
2.1. Glycine and Serine as Sources of One-Carbon Groups
2.2. Other Sources of One-Carbon Groups and Folates
3. Use of One-Carbon Groups on Tetrahydrofolates
3.1. Overview
3.2. Synthesis of Inosine Monophosphate and Deoxythymidine Monophosphate
3.3. Transfer of Methyl Groups to the Activated Methyl Group Cycle
3.4. Detoxification of Methanol
4. The Activated Methyl Group Cycle
4.1. Reactions of the Activated Methyl Group Cycle
4.2. Use of Methyl Groups From the Activated Methyl Group Cycle
5. Absorption of Cobalamin
6. Enzymes That Use Cobalamin as a Cofactor
6.1. Methionine Synthase
6.2. Methylmalonyl-CoA Mutase
7. Megaloblastic Anemia Due to Folate Deficiency or Cobalamin Deficiency
7.1. Folate Deficiency
7.2. Cobalamin Deficiency
8. Other Diseases Linked to Folates
8.1. Neural Tube Defects and Other Folate-Dependent Congenital Anomalies
8.2. Folates and Cancer
9. Transsulfuration Pathway and Metabolism of Cysteine
Summary
Further Reading
Review Questions
37 Pyrimidine Nucleotides and Chemotherapy
Learning Objectives
Synopsis
1. De Novo Synthesis of Uridine Monophosphate, a Precursor for All Pyrimidine Nucleotides
2. Synthesis and Uses of UTP and CTP
3. Reduction of Ribonucleotides to Deoxyribonucleotides
4. Synthesis of dTMP
5. Chemotherapeutic Agents That Interfere With dTMP Synthesis
5.1. 5-Fluorouracil and Related Drugs
5.2. Pemetrexed
5.3. Methotrexate
6. Degradation of Pyrimidine Nucleotides
Summary
Further Reading
Review Questions
38 Gout and Other Diseases Related to the Metabolism of Purine Nucleotides
Learning Objectives
Synopsis
1. De Novo Synthesis of Purine Nucleotides
2. Degradation and Salvage of Purine Nucleotides
2.1. Degradation of AMP and GMP to Hypoxanthine and Guanine
2.2. Degradation of Hypoxanthine to Xanthine and Urate
2.3. Excretion of Urate by the Kidneys
2.4. Salvage of Hypoxanthine and Guanine
2.5. Balancing the Production of IMP From Salvage and De Novo Synthesis
2.6. Daily Purine Turnover and Urate Excretion
3. Hyperuricemia
3.1. Plasma Urate as a Function of Gender and Age
3.2. Overproduction of Urate
3.3. Underexcretion of Urate
3.4. Plasma Urate and Preeclampsia
3.5. Crystallization of Urate
3.6. Tumor Lysis Syndrome
4. Gout
4.1. General Comments About Gout
4.2. Acute Gouty Arthritis
4.3. Uric Acid and Sodium Urate in Nephrolithiasis
5. Thiopurines
Summary
Further Reading
Review Questions
39 Diabetes
Learning Objectives
Synopsis
1. Overview of the Classification of Diabetes
2. Metabolism During Severe Insulin Deficiency
2.1. Diabetic Ketoacidosis
2.2. Hyperosmolar Hyperglycemic State
3. Diagnosis of Diabetes
4. Pathogenesis, Diagnosis, and Treatment of Type 1 Diabetes
4.1. Definitions
4.2. Pathogenesis, Heredity, and Diagnosis
4.3. Treatment of Type 1 Diabetes
5. Pathogenesis, Diagnosis, and Treatment of Type 2 Diabetes
5.1. Pathogenesis
5.2. Diagnosis
5.3. Treatment
6. MODY
7. Gestational Diabetes
8. Complications of Diabetes
8.1. General Comments
8.2. Clinical Aspects of Complications of Diabetes
8.3. Potential Biochemical Causes of Complications of Diabetes
8.3.1. Nonenzymatic Glycation
8.3.2. Damage by Reactive Oxygen Species
8.3.3. Deregulation of Metabolism
Summary
Further Reading
Review Questions
Answers to Review Questions
Chapter 1
Chapter 2
Chapter 3
Chapter 4
Chapter 5
Chapter 6
Chapter 7
Chapter 8
Chapter 9
Chapter 10
Chapter 11
Chapter 12
Chapter 13
Chapter 14
Chapter 15
Chapter 16
Chapter 17
Chapter 18
Chapter 19
Chapter 20
Chapter 21
Chapter 22
Chapter 23
Chapter 24
Chapter 25
Chapter 26
Chapter 27
Chapter 28
Chapter 29
Chapter 30
Chapter 31
Chapter 32
Chapter 33
Chapter 34
Chapter 35
Chapter 36
Chapter 37
Chapter 38
Chapter 39
Index
A
B
C
D
E
F
G
H
I
J
K
L
M
N
O
P
Q
R
S
T
U
V
W
X
Z
Copyright
Title Page
Dedication
Contents
Chapter 1: ‘I’m thinking’ – Oh, but are you?
Chapter 2: Renegade perception
Chapter 3: The Pushbacker sting
Chapter 4: ‘Covid’: The calculated catastrophe
Chapter 5: There is no ‘virus’
Chapter 6: Sequence of deceit
Chapter 7: War on your mind
Chapter 8: ‘Reframing’ insanity
Chapter 9: We must have it? So what is it?
Chapter 10: Human 2.0
Chapter 11: Who controls the Cult?
Chapter 12: Escaping Wetiko
Postscript
Appendix: Cowan-Kaufman-Morell Statement on Virus Isolation
Bibliography
Index