Principles of medical biochemistry

Part ONE PRINCIPLES OF MOLECULAR STRUCTURE AND FUNCTION 1 Chapter 1 INTRODUCTION TO BIOMOLECULES  Water Is the Solvent of Life  Water Contains Hydronium Ions and Hydroxyl Ions  Ionizable Groups Are Characterized by Their pK Values  The Blood pH is Tightly Regulated  Acidosis and Alkalosis Are Common in Clinical Practice  Bonds Are Formed by Reactions between Functional Groups  Isomeric Forms Are Common in Biomolecules  Properties of Biomolecules Are Determined by Their Noncovalent Interactions  Triglycerides Consist of Fatty Acids and Glycerol  Monosaccharides Are Polyalcohols with a Keto Group or an Aldehyde Group  Monosaccharides Form Ring Structures  Complex Carbohydrates Are Formed by Glycosidic Bonds  Polypeptides Are Formed from Amino Acids  Nucleic Acids Are Formed from Nucleotides  Most Biomolecules Are Polymers  Summary  Chapter 2 INTRODUCTION TO PROTEIN STRUCTURE  Amino Acids Are Zwitterions  Amino Acid Side Chains Form Many Noncovalent Interactions  Peptide Bonds and Disulfide Bonds Form the Primary Structure of Proteins  Proteins Can Fold Themselves into Many Shapes  ?-Helix and ?-Pleated Sheet Are the Most Common Secondary Structures in Proteins  Globular Proteins Have a Hydrophobic Core  Proteins Lose Their Biological Activities When Their Higher-Order Structure Is Destroyed  The Solubility of Proteins Depends on pH and Salt Concentration  Proteins Absorb Ultraviolet Radiation  Proteins Can Be Separated by Their Charge or Their Molecular Weight  Abnormal Protein Aggregates Can Cause Disease  Neurodegenerative Diseases Are Caused by Protein Aggregates  Protein Misfolding Can Be Contagious  Summary Chapter 3 OXYGEN TRANSPORTERS: HEMOGLOBIN AND MYOGLOBIN  The Heme Group Is the Oxygen-Binding Site of Hemoglobin and Myoglobin  Myoglobin Is a Tightly Packed Globular Protein  Red Blood Cells Are Specialized for Oxygen Transport  The Hemoglobins Are Tetrameric Proteins  Oxygenated and Deoxygenated Hemoglobin Have Different Quaternary Structures  Oxygen Binding to Hemoglobin Is Cooperative  2,3-Bisphosphoglycerate Is a Negative Allosteric Effector of Oxygen Binding to Hemoglobin  Fetal Hemoglobin Has a Higher Oxygen-Binding Affinity than Does Adult Hemoglobin  The Bohr Effect Facilitates Oxygen Delivery  Most Carbon Dioxide Is Transported as Bicarbonate  Summary 38 Chapter 4 ENZYMATIC REACTIONS 39 The Equilibrium Constant Describes the Equilibrium of the Reaction  The Free Energy Change Is the Driving Force for Chemical Reactions  The Standard Free Energy Change Determines the Equilibrium  Enzymes Are Both Powerful and Selective  The Substrate Must Bind to Its Enzyme before the Reaction Can Proceed  Rate Constants Are Useful for Describing Reaction Rates  Enzymes Decrease the Free Energy of Activation  Many Enzymatic Reactions Can Be Described by Michaelis-Menten Kinetics  Km and Vmax Can Be Determined Graphically  Substrate Half-Life Can Be Determined for First-Order but Not Zero-Order Reactions  Kcat/Km Predicts the Enzyme Activity at Low Substrate Concentration  Allosteric Enzymes Do Not Conform to Michaelis-Menten Kinetics  Enzyme Activity Depends on Temperature and pH  Different Types of Reversible Enzyme Inhibition Can Be Distinguished Kinetically  Enzymes Stabilize the Transition State  Chymotrypsin Forms a Transient Covalent Bond during Catalysis  Summary  Chapter 5 COENZYMES  Enzymes Are Classified According to Their Reaction Type  Adenosine Triphosphate Has Two Energy-Rich Bonds  ATP Is the Phosphate Donor in Phosphorylation Reactions  ATP Hydrolysis Drives Endergonic Reactions  Cells Always Try to Maintain a High Energy Charge  Dehydrogenase Reactions Require Specialized Coenzymes  Coenzyme A Activates Organic Acids  S-Adenosyl Methionine Donates Methyl Groups  Many Enzymes Require a Metal Ion  Summary  Part TWO GENETIC INFORMATION: DNA, RNA, AND PROTEIN SYNTHESIS  Chapter 6 DNA, RNA, AND PROTEIN SYNTHESIS  All Living Organisms Use DNA as Their Genetic Databank  DNA Contains Four Bases  DNA Forms a Double Helix  DNA Can Be Denatured DNA Is Supercoiled  DNA Replication Is Semiconservative  DNA Is Synthesized by DNA Polymerases  DNA Polymerases Have Exonuclease Activities  Unwinding Proteins Present a Single-Stranded Template to the DNA Polymerases  One of the New DNA Strands Is Synthesized Discontinuously  RNA Plays Key Roles in Gene Expression  The ? Subunit Recognizes Promoters  DNA Is Faithfully Copied into RNA  Some RNAs Are Chemically Modified after Transcription  The Genetic Code Defines the Structural Relationship between mRNA and Polypeptide  Transfer RNA Is the Adapter Molecule in Protein Synthesis  Amino Acids Are Activated by an Ester Bond with the 3' Terminus of the tRNA  Many Transfer RNAs Recognize More than One Codon  Ribosomes Are the Workbenches for Protein Synthesis  The Initiation Complex Brings Together Ribosome, Messenger RNA, and Initiator tRNA  Polypeptides Grow Stepwise from the Amino Terminus to the Carboxyl Terminus  Protein Synthesis Is Energetically Expensive  Gene Expression Is Tightly Regulated  A Repressor Protein Regulates Transcription of the lac Operon in E. coli  Anabolic Operons Are Repressed by the End Product of the Pathway  Glucose Regulates the Transcription of Many Catabolic Operons  Transcriptional Regulation Depends on DNA-Binding Proteins  Summary  Chapter 7 THE HUMAN GENOME  Chromatin Consists of DNA and Histones  The Nucleosome Is the Structural Unit of Chromatin  Covalent Histone Modifications Regulate DNA Replication and Transcription  DNA Methylation Silences Genes  All Eukaryotic Chromosomes Have a Centromere, Telomeres, and Replication Origins  Telomerase Is Required (but Not Sufficient) for Immortality  Eukaryotic DNA Replication Requires Three DNA Polymerases  Most Human DNA Does Not Code for Proteins  Gene Families Originate by Gene Duplication  The Genome Contains Many Tandem Repeats  Some DNA Sequences Are Copies of Functional RNAs  Many Repetitive DNA Sequences Are (or Were) Mobile  L1 Elements Encode a Reverse Transcriptase  Alu Sequences Spread with the Help of L1 Reverse Transcriptase  Mobile Elements Are Dangerous  Humans Have Approximately 20,000 Genes  Transcriptional Initiation Requires General Transcription Factors  Genes Are Surrounded by Regulatory Sites  Gene Expression Is Regulated by DNA-Binding Proteins  Long Non-coding RNAs Play Roles in Gene Expression  mRNA Processing Starts during Transcription  Translational Initiation Requires Many Initiation Factors  mRNA Processing and Translation Are Often Regulated  Small RNA Molecules Inhibit Gene Expression  Mitochondria Have Their Own DNA  Human Genomes Are Very Diverse  Human Genomes Have Many Low-Frequency Copy Number Variations  Summary  Chapter 8 PROTEIN TARGETING AND PROTEOSTASIS A Signal Sequence Directs Polypeptides to the Endoplasmic Reticulum  Glycoproteins Are Processed in the Secretory Pathway  The Endocytic Pathway Brings Proteins into the Cell  Lysosomes Are Organelles of Intracellular Digestion  Autophagy Recycles Cellular Proteins and Organelles  Poorly Folded Proteins Are Either Repaired or Destroyed  Ubiquitin Markes Proteins for Destruction  The Proteostatic System Protects Cells from Abnormal Proteins  Summary  Chapter 9 INTRODUCTION TO GENETIC DISEASES  Four Types of Genetic Disease  Mutations Occur in the Germline and in Somatic Cells  Mutations Are an Important Cause of Poor Health  Small Mutations Lead to Abnormal Proteins  Most Mutations Are Caused by Replication Errors  Mutations Can Be Induced by Radiation and Chemicals  Mismatch Repair Corrects Replication Errors  Missing Bases and Abnormal Bases Need to Be Replaced  Nucleotide Excision Repair Removes Bulky Lesions  Repair of DNA Double-Strand Breaks Is Difficult  Hemoglobin Genes Form Two Gene Clusters  Many Point Mutations in Hemoglobin Genes Are Known  Sickle Cell Disease Is Caused by a Point Mutation in the b-Chain Gene  SA Heterozygotes Are Protected from Tropical Malaria  ?-Thalassemia Is Most Often Caused by Large Deletions Many Different Mutations Can Cause ?-Thalassemia  Fetal Hemoglobin Protects from the Effects of ?-Thalassemia and Sickle Cell Disease  Summary  Chapter 10 VIRUSES  Viruses Can Replicate Only in a Host Cell  Bacteriophage T4 Destroys Its Host Cell  DNA Viruses Substitute Their Own DNA for the Host Cell DNA  ? Phage Can Integrate Its DNA into the Host Cell Chromosome  RNA Viruses Require an RNA-Dependent RNA Polymerase  Retroviruses Replicate Through a DNA Intermediate  Plasmids Are Small "Accessory Chromosomes" or "Symbiotic Viruses" of Bacteria  Bacteria Can Exchange Genes by Transformation and Transduction  Jumping Genes Can Change Their Position in the Genome  Summary  Chapter 11 DNA TECHNOLOGY  Restriction Endonucleases Cut Large DNA Molecules into Smaller Fragments  Large Probes Are Used to Detect Copy Number Variations  Small Probes Are Used to Detect Point Mutations  Southern Blotting Determines the Size of Restriction Fragments  DNA Can Be Amplified with the Polymerase Chain Reaction  PCR Is Used for Preimplantation Genetic Diagnosis  Allelic Heterogeneity Is the Greatest Challenge for Molecular Genetic Diagnosis  Normal Polymorphisms Are Used as Genetic Markers  Tandem Repeats Are Used for DNA Fingerprinting  DNA Microarrays Can Be Used for Genetic Screening  DNA Microarrays Are Used for the Study of Gene Expression  DNA Is Sequenced by Controlled Chain Termination  Massively Parallel Sequencing Permits Cost-Efficient Whole-Genome Genetic Diagnosis  Gene Therapy Targets Somatic Cells  Viruses Are Used as Vectors for Gene Therapy  Retroviruses Can Splice a Transgene into the Cell's Genome  Genome Editing Is Based on the Making and Healing of DNA Double Strand Breaks  Designer Nucleases Are Used for Genome Editing  Antisense Oligonucleotides Can Block the Expression of Rogue Genes  Genes Can Be Altered in Animals  Tissue-Specific Gene Expression Can Be Engineered into Animals  Human Germline Genome Editing is Technically Possible  Summary  Part THREE CELL AND TISSUE STRUCTURE  Chapter 12 BIOLOGICAL MEMBRANES  Membranes Consist of Lipid and Protein  Phosphoglycerides Are the Most Abundant Membrane Lipids  Most Sphingolipids Are Glycolipids  Cholesterol Is the Most Hydrophobic Membrane Lipid  Membrane Lipids Form a Bilayer  The Lipid Bilayer Is a Two-Dimensional Fluid  The Lipid Bilayer Is a Diffusion Barrier  Membranes Contain Integral and Peripheral Membrane Proteins  Membranes Are Asymmetrical  Membranes Are Fragile  Membrane Proteins Carry Solutes across the Lipid Bilayer  Transport against an Electrochemical Gradient Requires Metabolic Energy  Active Transport Consumes ATP  Sodium Cotransport Brings Molecules into the Cell  Summary  Chapter 13 THE CYTOSKELETON  The Erythrocyte Membrane Is Reinforced by a Spectrin Network  Keratins Give Strength to Epithelia  Actin Filaments Are Formed from Globular Subunits  Striated Muscle Contains Thick and Thin Filaments  Myosin Is a Two-Headed Molecule with ATPase Activity  Muscle Contraction Requires Calcium and ATP  The Cytoskeleton of Skeletal Muscle Is Linked to the Extracellular Matrix  Microtubules Consist of Tubulin  Eukaryotic Cilia and Flagella Contain a 9 + 2 Array of Microtubules  Cells Form Specialized Junctions with Other Cells and with the Extracellular Matrix  Summary  Chapter 14 THE EXTRACELLULAR MATRIX  Collagen Is the Most Abundant Protein in the Human Body Tropocollagen Molecule Forms a Long Triple Helix  Collagen Fibrils Are Staggered Arrays of Tropocollagen Molecules  Collagen Is Subject to Extensive Posttranslational Processing  Collagen Metabolism Is Altered in Aging and Disease  Many Genetic Defects of Collagen Structure and Biosynthesis Are Known  Elastic Fibers Contain Elastin and Fibrillin  The Amorphous Ground Substance Contains Hyaluronic Acid  Sulfated Glycosaminoglycans Are Covalently Bound to Core Proteins  Cartilage Contains Large Proteoglycan Aggregates  Proteoglycans Are Synthesized in the ER and Degraded in Lysosomes  Mucopolysaccharidoses Are Caused by Deficiency of Glycosaminoglycan-Degrading Enzymes  Bone Consists of Calcium Phosphates in a Collagenous Matrix  Basement Membranes Contain Type IV Collagen, Laminin, and Heparan Sulfate Proteoglycans  Fibronectin Glues Cells and Collagen Fibers Together  Summary Part FOUR MOLECULAR PHYSIOLOGY  Chapter 15 EXTRACELLULAR MESSENGERS  Steroid Hormones Are Made from Cholesterol  Progestins Are the Biosynthetic Precursors of All Other Steroid Hormones  Thyroid Hormones Are Synthesized from Protein-Bound Tyrosine  T4 Becomes Activiated to T3 in the Target Tissues  Both Hypothyroidism and Hyperthyroidism Are Common Disorders  Insulin Is Released Together with the C-Peptide  Proopiomelanocortin Forms Several Active Products  Angiotensin Is Formed from Circulating Angiotensinogen  Immunoassays Are Used for Determination of Hormone Levels  Catecholamines Are Synthesized from Tyrosine  Indolamines Are Synthesized from Tryptophan  Histamine Is Produced by Mast Cells and Basophils  Neurotransmitters Are Released at Synapses  Acetylcholine Is the Neurotransmitter of the Neuromuscular Junction  There Are Many Neurotransmitters  Summary  Chapter 16 INTRACELLULAR MESSENGERS  Receptor-Hormone Interactions Are Noncovalent, Reversible, and Saturable  Many Neurotransmitter Receptors Are Ion Channels  Steroid and Thyroid Hormones Bind to Transcription Factors  Seven-Transmembrane Receptors Are Coupled to G Proteins  Adenylate Cyclase Is Regulated by G Proteins  Hormones Can Both Activate and Inhibit the cAMP Cascade  Cytoplasmic Calcium Is an Important Intracellular Signal  Phospholipase C Generates Two Second Messengers  Both cAMP and Calcium Regulate Gene Transcription  Muscle Contraction and Exocytosis Are Triggered by Calcium  Atrial Natriuretic Factor Acts through a Membrane-Bound Guanylate Cyclase  Nitric Oxide Stimulates a Soluble Guanylate Cyclase  cGMP Is a Second Messenger in Retinal Rod Cells  Receptors for Insulin and Growth Factors Are Tyrosine-Specific Protein Kinases  Growth Factors and Insulin Trigger Multiple Signaling Cascades  Cytokin Receptors Use the JAK-Stat Pathway  Many Receptors Become Desensitized after Overstimulation  Summary  Chapter 17 PLASMA PROTEINS  The Blood pH Is Tightly Regulated  Acidosis and Alkalosis Are Common in Clinical Practice  Plasma Proteins Are Both Synthesized and Destroyed in the Liver  Albumin Prevents Edema  Albumin Binds Many Small Molecules  Some Plasma Proteins Are Specialized Carriers of Small Molecules  Deficiency of ?1-Antiprotease Causes Lung Emphysema  Levels of Plasma Proteins Are Affected by Many Diseases  Blood Components Are Used for Transfusions  Blood Clotting Must Be Tightly Controlled  Platelets Adhere to Exposed Subendothelial Tissue  Insoluble Fibrin Is Formed from Soluble Fibrinogen  Thrombin Is Derived from Prothrombin  Factor X Can Be Activated by the Extrinsic and Intrinsic Pathways  Negative Controls Are Necessary to Prevent Thrombosis  Plasmin Degrades the Fibrin Clot  Heparin and the Vitamin K Antagonists Are Used as Anticoagulants  Clotting Factor Deficiencies Cause Abnormal Bleeding  Tissue Damage Causes Release of Cellular Enzymes into Blood  Serum Enzymes Are Used for the Diagnosis of Many Diseases  Summary  Chapter 18 Defense Mechanisms  Lipophilic Xenobiotics Are Metabolized to Water-soluble Products  Cytochrome P-450 Is Involved in Phase I Metabolism Phase II Metabolism Makes Xenobiotics Water-Soluble for Excretion Phase III Metabolism Excretes Xenobiotic Metabolites  Drug Metabolizing Enzymes Are Inducible  The Innate Immune System Uses Pattern Recognitino Receptors  Infection Triggers Inflammation  Lymphocytes Possess Antigen Receptors  B Lymphocytes Produce Immunoglobulins  Antiboidies Consist of Two Light Chains and Two Heavy Chains  Different Immunoglobulin Classes Have Different Properties  Adaptive Immune Responses Are Based on Clonal Selection  Immunoglobulin genes Are Rearranged During B-Cell Development  The T-Cell Receptor Recruits Cytosolic Tyrosine Protein Kinases  Mediatros of Inflammation Are Produced form Arachidonic Acid Prostaglandins Are Synthesized in All Tissues  Prostanoids Participate in Many Physiological Processes  Leukotrienes Are Produced by the Lipoxygenase Pathway  Anti-Inflammatory Drugs Inhibit the Synthesis of Eicosanoids Summary  Chapter 19 CELLULAR GROWTH CONTROL AND CANCER  The Cell Cycle Is Controlled at Two Checkpoints  Cells Can Be Grown in Culture  Cyclins Play Key Roles in Cell Cycle Control  Retinoblastoma Protein Guards the G1 Checkpoint  Cell Proliferation Is Triggered by Mitogens  Mitogens Regulate Gene Expression  Cells Can Commit Suicide  Cancers Are Monoclonal in Origin  Cancer Is Caused by Activation of Growth-Promoting Genes and Inactivation of Growth-Inhibiting Genes  Some Retroviruses Contain an Oncogene  Retroviruses Can Cause Cancer by Inserting Themselves Next to a Cellular Proto-Oncogene  Many Oncogenes Code for Components of Mitogenic Signaling Cascades  Cancer Susceptibility Syndromes Are Caused by Inherited Mutations in Tumor Suppressor Genes  Many Tumor Suppressor Genes Are Known  Components of the Cell Cycle Machinery Are Abnormal in Most Cancers  DNA Damage Causes Either Growth Arrest or Apoptosis  Most Spontaneous Cancers Are Defective in p53 Action  The P13K/Protein Kinase B Pathway Is Activated in Many Cancers  The Products of Some Viral Oncogenes Neutralize the Products of Cellular Tumor Suppressor Genes  Tumors Become More Malignant through Darwinian Selection  Intestinal Polyps Are Benign Lesions  Intestinal Polyps Can Evolve into Colon Cancer  Summary  Part FIVE METABOLISM  Chapter 20 DIGESTIVE ENZYMES  Saliva Contains ?-Amylase and Lysozyme  Protein and Fat Digestion Start in the Stomach  The Pancreas Is a Factory for Digestive Enzymes  Fat Digestion Requires Bile Salts  Some Digestive Enzymes Are Anchored to the Surface of the Microvilli  Poorly Digestible Nutrients Cause Flatulence  Many Digestive Enzymes Are Released as Inactive Precursors  Summary  Chapter 21 INTRODUCTION TO METABOLIC PATHWAYS  Alternative Substrates Can Be Oxidized in the Body Metabolic Processes Are Compartmentalized  Free Energy Changes in Metabolic Pathways Are  Additive  Most Metabolic Pathways Are Regulated  Feedback Inhibition and Feedforward Stimulation Are the Most Important Regulatory Principles  Metabolism Is Regulated to Ensure Homeostasis  Inherited Enzyme Deficiencies Cause Metabolic Diseases  Vitamin Deficiencies, Toxins, and Endocrine Disorders Can Disrupt Metabolic Pathways  Summary  Chapter 22 GLYCOLYSIS, TRICARBOXYLIC ACID CYCLE, AND OXIDATIVE PHOSPHORYLATION  Glucose Uptake into the Cells Is Regulated  Glucose Degradation Begins in the Cytoplasm and Ends in the Mitochondria  Glycolysis Begins with ATP-Dependent Phosphorylations  Most Glycolytic Intermediates Have Three Carbons  Phosphofructokinase Is the Most Important Regulated Enzyme of Glycolysis  Lactate Is Produced under Anaerobic Conditions  Pyruvate Is Decarboxylated to Acetyl-CoA in the Mitochondria  The TCA Cycle Produces Two Molecules of Carbon Dioxide for Each Acetyl Residue  Reduced Coenzymes Are the Most Important Products of the TCA Cycle  Oxidative Pathways Are Regulated by Energy Charge and [NADH]/[NAD+] Ratio  TCA Cycle Provides an Important Pool of Metabolic Intermediates  Antiporters Transport Metabolites across the Inner Mitochondrial Membrane  The Respiratory Chain Channels Electrons fromNADH and FADH2 to Molecular Oxygen  Standard Reduction Potential Is the Tendency to Donate Electrons  The Respiratory Chain Contains Flavoproteins, Iron-Sulfur Proteins, Cytochromes, Ubiquinone, and Protein-Bound Copper  The Respiratory Chain Contains Large Multiprotein Complexes  The Respiratory Chain Creates a Proton Gradient  The Proton Gradient Drives ATP Synthesis  The Efficiency of Glucose Oxidation Is Close to 40%  Oxidative Phosphorylation Is Limited by the Supply of ADP  Brown Adipose Tissue Contains an Uncoupling Protein  Mutations in Mitochondrial DNA Can Cause Disease  Summary  Chapter 23 Oxygen Deficiency and Oxygen Toxicity  Ischemia Leads to Infarction  Oxidative Phosphorylation Is Inhibited by Many Poisons  Hypoxia Inducible Factor Adjusts Cell Metabolism to Hypoxia  Reactive Oxygen Derivatives Are Formed during Oxidative Metabolism  The Respiratory Chain Is a Major Source of Superoxide  Cells Have Specialized Enzymes to Destroy Reactive Oxygen Species  Free Radical Formation Is Affected by Energy Supply and Energy Consumption  Some Vitamins and Phytochemicals Can Scavange Free Radicals  The NRF2 Transcription Factor Coordinates Defenses against Reactive Oxygen Species  Phagocytic Cells Use Reactive Oxygen Species for Intracellular Killing  Summary  Chapter 24 CARBOHYDRATE METABOLISM  An Adequate Blood Glucose Level Must Be Maintained at All Times  Gluconeogenesis Bypasses the Three Irreversible Reactions of Glycolysis  Fatty Acids Cannot Be Converted into Glucose  Glycolysis and Gluconeogenesis Are Regulated by Hormones  Glycolysis and Gluconeogenesis Are Fine Tuned by Allosteric Effectors and Hormone-Induced Enzyme Phosphorylations  Fructose-2,6-biphosphate Switches the Liver from Gluconeogenesis to Glycolysis  Glucokinase Is Regulated by Two Regulatory Proteins  Carbohydrate Is Stored as Glycogen  Glycogen Is 0Synthesized from Glucose  Glycogen Is Degraded by Phosphorolytic Cleavage  Glycogen Metabolism Is Regulated by Hormones and Metabolites  Glycogen Accumulates in Several Enzyme Deficiencies  Fructose Is Channeled into Glycolysis/Gluconeogenesis  Excess Fructose Is Problematic Excess Galactose Is Channeled into the Pathways of Glucose Metabolism  The Pentose Phosphate Pathway Supplies NADPH and Ribose-5-Phosphate  Fructose Is the Principal Sugar in Seminal Fluid  Amino Sugars and Sugar Acids Are Made from Glucose  Summary  Chapter 25 THE METABOLISM OF FATTY ACIDS AND TRIGLYCERIDES  Fatty Acids Differ in Their Chain Length and Number of Double Bonds  Chylomicrons Transport Triglycerides from the Intestine to Other Tissues  Adipose Tissue Is Specialized for the Storage of Triglycerides  Fat Metabolism in Adipose Tissue Is under Hormonal Control  Fatty Acids Are Transported into the Mitochondrion  ?-Oxidation Produces Acetyl-CoA, NADH, and FADH2  Special Fatty Acids Require Special Reactions  The Liver Converts Excess Fatty Acids to Ketone Bodies  Fatty Acids Are Synthesized from Acetyl-CoA  Acetyl-CoA Is Shuttled into the Cytoplasm as Citrate  Fatty Acid Synthesis Is Regulated by Hormones and Metabolites  AMP-Activated Protein Kinase Adapts Metabolic Pathways to Cellular Energy Status  Most Fatty Acids Can Be Synthesized from Palmitate  Fatty Acids Regulate Gene Expression  Polyunsaturated Fatty Acids Can Be Oxidized Nonenzymatically Summary  Chapter 26 THE METABOLISM OF MEMBRANE LIPIDS 000Phosphatidic Acid Is an Intermediate in Phosphoglyceride Synthesis  Phosphoglycerides Are Remodeled Continuously  Sphingolipids Are Synthesized from Ceramide  Deficiencies of Sphingolipid-Degrading Enzymes Cause Lipid Storage Diseases  Cholesterol Is the Least Soluble Membrane Lipid  Cholesterol Is Derived from Both Endogenous Synthesis and the Diet  Cholesterol Biosynthesis Is Regulated at the Level of HMG-CoA Reductase  Bile Acids Are Synthesized from Cholesterol  Bile Acids Are Subject to Extensive Enterohepatic Circulation  Most Gallstones Consist of Cholesterol  Summary  Chapter 27 LIPID TRANSPORT  Most Plasma Lipids Are Components of Lipoproteins  Lipoproteins Have Characteristic Lipid and Protein Compositions  Dietary Lipids Are Transported by Chylomicrons  VLDL Is a Precursor of LDL  LDL Is Removed by Receptor-Mediated Endocytosis  Cholesterol Regulates Its Own Metabolism  HDL Is Needed for Reverse Cholesterol Transport  Lipoproteins Can Initiate Atherosclerosis  Lipoproteins Respond to Diet and Lifestyle  Hyperlipoproteinemias Are Grouped into Five Phenotypes  Hyperlipidemias Are Treated with Diet and Drugs Summary  Chapter 26 AMINO ACID METABOLISM  Amino Acids Can Be Used for Gluconeogenesis and Ketogenesis  The Nitrogen Balance Indicates the Net Rate of Protein Synthesis  The Amino Group of Amino Acids Is Released as Ammonia  Ammonia Is Detoxified to Urea  Urea Is Synthesized in the Urea Cycle  Hyperammonemia Can Be Treated with Diet and Drugs  Some Amino Acids Are Closely Related to Common Metabolic Intermediates  Glycine, Serine, and Threonine Are Glucogenic  Proline, Arginine, Ornithine, and Histidine Are Degraded to Glutamate  Methionine and Cysteine Are Metabolically Related  Valine, Leucine, and Isoleucine Are Degraded by Transamination and Oxidative Decarboxylation  Phenylalanine and Tyrosine Are Both Glucogenic and Ketogenic Melanin Is Shesized from Tyrosine  Lysine and Tryptophan Have Lengthy Catabolic Pathways  The Liver Is the Most Important Organ of Amino Acid Metabolism  Glutamine Participates in Renal Acid-Base Regulation  Summary  Chapter 29 METABOLISM OF IRON AND HEME Iron Is Conserved Very Efficiently in the Body  Iron Uptake by Cells Is Regulated  Dietary Iron Is Absorbed in the Duodenum  Dietary Iron Absorption Is Regulated  Iron Deficiency Is the Most Common Micronutrient Deficiency Worldwide  Bone Marrow and Liver Are the Most Important Sites of Heme Synthesis  Heme Is Synthesized from Succinyl-Coenzyme A and Glycine  Porphyrias Are Caused by Deficiencies of Heme-Synthesizing Enzymes  Heme Is Degraded to Bilirubin  Bilirubin Is Conjugated and Excreted by the Liver  Elevations of Serum Bilirubin Cause Jaundice  Many Diseases Can Cause Jaundice  Summary  Chapter 30 THE METABOLISM OF PURINES AND PYRIMIDINES  Purine Synthesis Starts with Ribose-5-Phosphate  Purines Are Degraded to Uric Acid  Free Purine Bases Can Be Salvaged  Pyrimidines Are Synthesized from Carbamoyl Phosphate and Aspartate  DNA Synthesis Requires Deoxyribonucleotides  Many Antineoplastic Drugs Inhibit Nucleotide Metabolism  Uric Acid Has Limited Water Solubility  Hyperuricemia Causes Gout  Abnormalities of Purine-Metabolizing Enzymes Can Cause Gout  Gout Can Be Treated with Drugs  Summary  Chapter 31 MICRONUTRIENTS  Riboflavin Is a Precursor of Flavin Mononucleotide and Flavin Adenine Dinucleotide  Niacin Is a Precursor of NAD and NADP  Thiamin Deficiency Causes Weakness and Amnesia  Vitamin B6 Plays a Key Role in Amino Acid Metabolism  Pantothenic Acid Is a Building Block of Coenzyme A  Biotin Is a Coenzyme in Carboxylation Reactions  Folic Acid Deficiency Causes Megaloblastic Anemia  Vitamin B12 Requires Intrinsic Factor for Its Absorption  Vitamin C Is a Water-Soluble Antioxidant  Retinol, Retinal, and Retinoic Acid Are the Active Forms of Vitamin A  Vitamin D Is a Prohormone  Vitamin E Prevents Lipid Oxidation  Many Vitamins and Phytochemicals Are Antioxidants  Vitamin K Is Required for Blood Clotting  Zinc Is a Constituent of Many Enzymes Copper Participates in Reactions of Molecular Oxygen  Some Trace Elements Serve Very Specific Functions  Summary  Chapter 32 INTEGRATION OF METABOLISM  Insulin Is Released in Response to Elevated Glucose  Insulin Stimulates the Utilization of Nutrients  Protein Synthesis Is Coordinated by the mTOR Complex  Glucagon Maintains the Blood Glucose Level  Catecholamines Mediate the Flight-or-Fight Response  Glucocorticoids Are Released in Chronic Stress  Energy Is Expended Continuously  Stored Fat and Glycogen Are Degraded between Meals  Adipose Tissue Is the Most Important Energy Depot  The Liver Converts Dietary Carbohydrates to Glycogen and Fat after a Meal  The Liver Maintains the Blood Glucose Level during Fasting  Ketone Bodies Provide Lipid-Based Energy during Fasting  Obesity Is Common  in All Affluent Countries  Appetite Control Is the Most Important Determinant of Obesity  Obesity Is Related to Insulin Resistance  Diabetes Is Caused by Insulin Deficiency or Insulin Resistance  In Diabetes, Metabolism Is Regulated as in Starvation  Diabetes Is Diagnosed with Laboratory Tests  Diabetes Leads to Late Complications  Many Drugs Are Available for Diabetes Treatment  Contracting Muscle Has Three Energy Sources  Catecholamines Coordinate Metabolism during Exercise  Physical Exercise Leads to Adaptive Changes  Ethanol Is Metabolized to Acetyl-CoA in the Liver  Liver Metabolism Is Deranged by Alcohol  Alcoholism Leads to Fatty Liver and Liver Cirrhosis  Most "Diseases of Civilization" Are Caused by Aberrant Livestyles  Aging Is the Greatest Challenge for Medical Research Anti-Aging Treatments Are Being Investigated  Summary  ANSWERS TO QUESTIONS  GLOSSARY  CREDITS  EXTRA ONLINE-ONLY CASE STUDIES {more new Cases to be added, to come} The Mafia Boss Viral Gastroenteritis Death in Installments A Mysterious Death To Treat or Not to Treat? Yellow Eyes An Abdominal Emergency Shortness of Breath Itching Abdominal Pain Rheumatism A Bank Manager in Trouble Kidney Problems Gender Blender Man Overboard! Spongy Bones Blisters The Sunburned Child Too Much Ammonia ANSWERS TO CASE STUDIES