Part ONE PRINCIPLES OF MOLECULAR STRUCTURE AND FUNCTION 1<br>Chapter 1 INTRODUCTION TO BIOMOLECULES<br>Water Is the Solvent of Life<br>Water Contains Hydronium Ions and Hydroxyl Ions<br>Ionizable Groups Are Characterized by Their pK Values<br>The Blood pH is Tightly Regulated<br>Acidosis and Alkalosis Are Common in Clinical Practice<br>Bonds Are Formed by Reactions between Functional Groups<br>Isomeric Forms Are Common in Biomolecules<br>Properties of Biomolecules Are Determined by Their Noncovalent<br>Interactions<br>Triglycerides Consist of Fatty Acids and Glycerol<br>Monosaccharides Are Polyalcohols with a Keto Group or an<br>Aldehyde Group<br>Monosaccharides Form Ring Structures<br>Complex Carbohydrates Are Formed by Glycosidic Bonds<br>Polypeptides Are Formed from Amino Acids<br>Nucleic Acids Are Formed from Nucleotides<br>Most Biomolecules Are Polymers<br>Summary<br>Chapter 2 INTRODUCTION TO PROTEIN STRUCTURE<br>Amino Acids Are Zwitterions<br>Amino Acid Side Chains Form Many Noncovalent<br>Peptide Bonds and Disulfide Bonds Form the Primary Structure of<br>Proteins<br>Proteins Can Fold Themselves into Many Shapes<br>α-Helix and β-Pleated Sheet Are the Most Common Secondary<br>Structures in Proteins<br>Globular Proteins Have a Hydrophobic Core<br>Proteins Lose Their Biological Activities When Their Higher-Order<br>Structure Is Destroyed<br>The Solubility of Proteins Depends on pH and Salt<br>Concentration<br>Proteins Absorb Ultraviolet Radiation<br>Proteins Can Be Separated by Their Charge or Their Molecular<br>Weight<br>Abnormal Protein Aggregates Can Cause Disease<br>Neurodegenerative Diseases Are Caused by Protein Aggregates<br>Protein Misfolding Can Be Contagious<br>Chapter 3 OXYGEN TRANSPORTERS: HEMOGLOBIN AND MYOGLOBIN<br>The Heme Group Is the Oxygen-Binding Site of Hemoglobin and<br>Myoglobin Is a Tightly Packed Globular Protein<br>Red Blood Cells Are Specialized for Oxygen Transport<br>The Hemoglobins Are Tetrameric Proteins<br>Oxygenated and Deoxygenated Hemoglobin Have Different<br>Quaternary Structures<br>Oxygen Binding to Hemoglobin Is Cooperative<br>2,3-Bisphosphoglycerate Is a Negative Allosteric Effector of<br>Oxygen Binding to Hemoglobin<br>Fetal Hemoglobin Has a Higher Oxygen-Binding Affinity than<br>Does Adult Hemoglobin<br>The Bohr Effect Facilitates Oxygen Delivery<br>Most Carbon Dioxide Is Transported as Bicarbonate<br>Summary 38<br>Chapter 4 ENZYMATIC REACTIONS 39<br>The Equilibrium Constant Describes the Equilibrium of the<br>Reaction<br>The Free Energy Change Is the Driving Force for Chemical<br>Reactions<br>The Standard Free Energy Change Determines the Equilibrium<br>Enzymes Are Both Powerful and Selective<br>The Substrate Must Bind to Its Enzyme before the Reaction Can<br>Proceed<br>Rate Constants Are Useful for Describing Reaction Rates<br>Enzymes Decrease the Free Energy of Activation<br>Many Enzymatic Reactions Can Be Described by Michaelis-Menten<br>Kinetics<br>K<sub>m</sub> and V<sub>max</sub> Can Be Determined Graphically<br>Substrate Half-Life Can Be Determined for First-Order but Not<br>Zero-Order Reactions<br>K<sub>cat/</sub>K<sub>m</sub> Predicts the Enzyme Activity at Low Substrate<br>Allosteric Enzymes Do Not Conform to Michaelis-Menten<br>Enzyme Activity Depends on Temperature and pH<br>Different Types of Reversible Enzyme Inhibition Can Be<br>Distinguished Kinetically<br>Enzymes Stabilize the Transition State<br>Chymotrypsin Forms a Transient Covalent Bond during<br>Catalysis<br>Chapter 5 COENZYMES<br>Enzymes Are Classified According to Their Reaction Type<br>Adenosine Triphosphate Has Two Energy-Rich Bonds<br>ATP Is the Phosphate Donor in Phosphorylation Reactions<br>ATP Hydrolysis Drives Endergonic Reactions<br>Cells Always Try to Maintain a High Energy Charge<br>Dehydrogenase Reactions Require Specialized Coenzymes<br>Coenzyme A Activates Organic Acids<br>S-Adenosyl Methionine Donates Methyl Groups<br>Many Enzymes Require a Metal Ion<br><br>Part TWOGENETIC INFORMATION: DNA, RNA, AND PROTEIN SYNTHESIS<br>Chapter 6 DNA, RNA, AND PROTEIN SYNTHESIS<br>All Living Organisms Use DNA as Their Genetic Databank<br>DNA Contains Four Bases<br>DNA Forms a Double Helix<br>DNA Can Be Denatured<br>DNA Is Supercoiled<br>DNA Replication Is Semiconservative<br>DNA Is Synthesized by DNA Polymerases<br>DNA Polymerases Have Exonuclease Activities<br>Unwinding Proteins Present a Single-Stranded Template to the<br>DNA Polymerases<br>One of the New DNA Strands Is Synthesized Discontinuously<br>RNA Plays Key Roles in Gene Expression<br>The Σ Subunit Recognizes Promoters<br>DNA Is Faithfully Copied into RNA<br>Some RNAs Are Chemically Modified after Transcription<br>The Genetic Code Defines the Structural Relationship between mRNA and Polypeptide<br>Transfer RNA Is the Adapter Molecule in Protein Synthesis<br>Amino Acids Are Activated by an Ester Bond with the 3ˈ Terminus<br>of the tRNA<br>Many Transfer RNAs Recognize More than One Codon<br>Ribosomes Are the Workbenches for Protein Synthesis<br>The Initiation Complex Brings Together Ribosome, Messenger<br>RNA, and Initiator tRNA<br>Polypeptides Grow Stepwise from the Amino Terminus to the<br>Carboxyl Terminus<br>Protein Synthesis Is Energetically Expensive<br>Gene Expression Is Tightly Regulated<br>A Repressor Protein Regulates Transcription of the lac Operon<br>in E. coli<br>Anabolic Operons Are Repressed by the End Product of the<br>Pathway<br>Glucose Regulates the Transcription of Many Catabolic<br>Operons<br>Transcriptional Regulation Depends on DNA-Binding<br>Chapter 7<br>THE HUMAN GENOME<br>Chromatin Consists of DNA and Histones<br>The Nucleosome Is the Structural Unit of Chromatin<br>Covalent Histone Modifications Regulate DNA Replication and<br>Transcription<br>DNA Methylation Silences Genes<br>All Eukaryotic Chromosomes Have a Centromere, Telomeres, and<br>Replication Origins<br>Telomerase Is Required (but Not Sufficient) for Immortality<br>Eukaryotic DNA Replication Requires Three DNA<br>Polymerases<br>Most Human DNA Does Not Code for Proteins<br>Gene Families Originate by Gene Duplication<br>The Genome Contains Many Tandem Repeats<br>Some DNA Sequences Are Copies of Functional RNAs<br>Many Repetitive DNA Sequences Are (or Were) Mobile<br>L1 Elements Encode a Reverse Transcriptase<br>Alu Sequences Spread with the Help of L1 Reverse<br>Transcriptase<br>Mobile Elements Are Dangerous<br>Humans Have Approximately 20,000 Genes<br>Transcriptional Initiation Requires General Transcription<br>Factors<br>Genes Are Surrounded by Regulatory Sites<br>Gene Expression Is Regulated by DNA-Binding Proteins<br>Long Non-coding RNAs Play Roles in Gene Expression<br>mRNA Processing Starts during Transcription<br>Translational Initiation Requires Many Initiation Factors<br>mRNA Processing and Translation Are Often Regulated<br>Small RNA Molecules Inhibit Gene Expression<br>Mitochondria Have Their Own DNA<br>Human Genomes Are Very Diverse<br>Human Genomes Have Many Low-Frequency Copy Number<br>Variations<br>Chapter 8 PROTEIN TARGETING AND PROTEOSTASIS<br>A Signal Sequence Directs Polypeptides to the Endoplasmic<br>Reticulum<br>Glycoproteins Are Processed in the Secretory Pathway<br>The Endocytic Pathway Brings Proteins into the Cell<br>Lysosomes Are Organelles of Intracellular Digestion<br>Autophagy Recycles Cellular Proteins and Organelles<br>Poorly Folded Proteins Are Either Repaired or Destroyed<br>Ubiquitin Markes Proteins for Destruction<br>The Proteostatic System Protects Cells from Abnormal Proteins<br>Chapter 9 INTRODUCTION TO GENETIC DISEASES<br>Four Types of Genetic Disease<br>Mutations Occur in the Germline and in Somatic Cells<br>Mutations Are an Important Cause of Poor Health<br>Small Mutations Lead to Abnormal Proteins<br>Most Mutations Are Caused by Replication Errors<br>Mutations Can Be Induced by Radiation and Chemicals<br>Mismatch Repair Corrects Replication Errors<br>Missing Bases and Abnormal Bases Need to Be Replaced<br>Nucleotide Excision Repair Removes Bulky Lesions<br>Repair of DNA Double-Strand Breaks Is Difficult<br>Hemoglobin Genes Form Two Gene Clusters<br>Many Point Mutations in Hemoglobin Genes Are Known<br>Sickle Cell Disease Is Caused by a Point Mutation in the b-Chain<br>Gene<br>SA Heterozygotes Are Protected from Tropical Malaria<br>α-Thalassemia Is Most Often Caused by Large Deletions<br>Many Different Mutations Can Cause β-Thalassemia<br>Fetal Hemoglobin Protects from the Effects of β-Thalassemia and<br>Sickle Cell Disease<br>Chapter 10 VIRUSES<br>Viruses Can Replicate Only in a Host Cell<br>Bacteriophage T<sub>4</sub> Destroys Its Host Cell<br>DNA Viruses Substitute Their Own DNA for the Host Cell<br>DNA<br>λ Phage Can Integrate Its DNA into the Host Cell<br>Chromosome<br>RNA Viruses Require an RNA-Dependent RNA Polymerase<br>Retroviruses Replicate Through a DNA Intermediate<br>Plasmids Are Small "Accessory Chromosomes" or "Symbiotic<br>Viruses" of Bacteria<br>Bacteria Can Exchange Genes by Transformation and<br>Transduction<br>Jumping Genes Can Change Their Position in the Genome<br>Chapter 11 DNA TECHNOLOGY<br>Restriction Endonucleases Cut Large DNA Molecules into Smaller<br>Fragments<br>Large Probes Are Used to Detect Copy Number Variations<br>Small Probes Are Used to Detect Point Mutations<br>Southern Blotting Determines the Size of Restriction<br>DNA Can Be Amplified with the Polymerase Chain Reaction<br>PCR Is Used for Preimplantation Genetic Diagnosis<br>Allelic Heterogeneity Is the Greatest Challenge for Molecular<br>Genetic Diagnosis<br>Normal Polymorphisms Are Used as Genetic Markers<br>Tandem Repeats Are Used for DNA Fingerprinting<br>DNA Microarrays Can Be Used for Genetic Screening<br>DNA Microarrays Are Used for the Study of Gene Expression<br>DNA Is Sequenced by Controlled Chain Termination<br>Massively Parallel Sequencing Permits Cost-Efficient<br>Whole-Genome Genetic Diagnosis<br>Gene Therapy Targets Somatic Cells<br>Viruses Are Used as Vectors for Gene Therapy<br>Retroviruses Can Splice a Transgene into the Cell’s Genome<br>Genome Editing Is Based on the Making and Healing of DNA Double Strand Breaks<br>Designer Nucleases Are Used for Genome Editing<br>Antisense Oligonucleotides Can Block the Expression of Rogue<br>Genes<br>Genes Can Be Altered in Animals<br>Tissue-Specific Gene Expression Can Be Engineered into<br>Animals<br>Human Germline Genome Editing is Technically Possible<br><br>Part THREE CELL AND TISSUE STRUCTURE<br>Chapter 12 BIOLOGICAL MEMBRANES<br>Membranes Consist of Lipid and Protein<br>Phosphoglycerides Are the Most Abundant Membrane Lipids<br>Most Sphingolipids Are Glycolipids<br>Cholesterol Is the Most Hydrophobic Membrane Lipid<br>Membrane Lipids Form a Bilayer<br>The Lipid Bilayer Is a Two-Dimensional Fluid<br>The Lipid Bilayer Is a Diffusion Barrier<br>Membranes Contain Integral and Peripheral Membrane<br>Membranes Are Asymmetrical<br>Membranes Are Fragile<br>Membrane Proteins Carry Solutes across the Lipid Bilayer<br>Transport against an Electrochemical Gradient Requires Metabolic<br>Energy<br>Active Transport Consumes ATP<br>Sodium Cotransport Brings Molecules into the Cell<br>Chapter 13 THE CYTOSKELETON<br>The Erythrocyte Membrane Is Reinforced by a Spectrin<br>Network<br>Keratins Give Strength to Epithelia<br>Actin Filaments Are Formed from Globular Subunits<br>Striated Muscle Contains Thick and Thin Filaments<br>Myosin Is a Two-Headed Molecule with ATPase Activity<br>Muscle Contraction Requires Calcium and ATP<br>The Cytoskeleton of Skeletal Muscle Is Linked to the Extracellular<br>Matrix<br>Microtubules Consist of Tubulin<br>Eukaryotic Cilia and Flagella Contain a 9 + 2 Array of<br>Microtubules<br>Cells Form Specialized Junctions with Other Cells and with the<br>Extracellular Matrix<br>Chapter 14 THE EXTRACELLULAR MATRIX<br>Collagen Is the Most Abundant Protein in the Human Body<br>Tropocollagen Molecule Forms a Long Triple Helix<br>Collagen Fibrils Are Staggered Arrays of Tropocollagen<br>Molecules<br>Collagen Is Subject to Extensive Posttranslational Processing<br>Collagen Metabolism Is Altered in Aging and Disease<br>Many Genetic Defects of Collagen Structure and Biosynthesis Are<br>Known<br>Elastic Fibers Contain Elastin and Fibrillin<br>The Amorphous Ground Substance Contains Hyaluronic Acid<br>Sulfated Glycosaminoglycans Are Covalently Bound to Core<br>Cartilage Contains Large Proteoglycan Aggregates<br>Proteoglycans Are Synthesized in the ER and Degraded in<br>Lysosomes<br>Mucopolysaccharidoses Are Caused by Deficiency of<br>Glycosaminoglycan-Degrading Enzymes<br>Bone Consists of Calcium Phosphates in a Collagenous<br>Basement Membranes Contain Type IV Collagen, Laminin,<br>and Heparan Sulfate Proteoglycans<br>Fibronectin Glues Cells and Collagen Fibers Together<br><br>Part FOUR MOLECULAR PHYSIOLOGY<br>Chapter 15 EXTRACELLULAR MESSENGERS<br>Steroid Hormones Are Made from Cholesterol<br>Progestins Are the Biosynthetic Precursors of All Other Steroid<br>Hormones<br>Thyroid Hormones Are Synthesized from Protein-Bound<br>Tyrosine<br>T<sub>4</sub> Becomes Activiated to T<sub>3</sub> in the Target Tissues<br>Both Hypothyroidism and Hyperthyroidism Are Common<br>Disorders<br>Insulin Is Released Together with the C-Peptide<br>Proopiomelanocortin Forms Several Active Products<br>Angiotensin Is Formed from Circulating Angiotensinogen<br>Immunoassays Are Used for Determination of Hormone Levels<br>Catecholamines Are Synthesized from Tyrosine<br>Indolamines Are Synthesized from Tryptophan<br>Histamine Is Produced by Mast Cells and Basophils<br>Neurotransmitters Are Released at Synapses<br>Acetylcholine Is the Neurotransmitter of the Neuromuscular<br>Junction<br>There Are Many Neurotransmitters<br>Chapter 16 INTRACELLULAR MESSENGERS<br>Receptor-Hormone Interactions Are Noncovalent, Reversible,<br>and Saturable<br>Many Neurotransmitter Receptors Are Ion Channels<br>Steroid and Thyroid Hormones Bind to Transcription Factors<br>Seven-Transmembrane Receptors Are Coupled to G Proteins<br>Adenylate Cyclase Is Regulated by G Proteins<br>Hormones Can Both Activate and Inhibit the cAMP Cascade<br>Cytoplasmic Calcium Is an Important Intracellular Signal<br>Phospholipase C Generates Two Second Messengers<br>Both cAMP and Calcium Regulate Gene Transcription<br>Muscle Contraction and Exocytosis Are Triggered by Calcium<br>Atrial Natriuretic Factor Acts through a Membrane-Bound Guanylate Cyclase<br>Nitric Oxide Stimulates a Soluble Guanylate Cyclase<br>cGMP Is a Second Messenger in Retinal Rod Cells<br>Receptors for Insulin and Growth Factors Are Tyrosine-Specific<br>Protein Kinases<br>Growth Factors and Insulin Trigger Multiple Signaling<br>Cascades<br>Cytokin Receptors Use the JAK-Stat Pathway<br>Many Receptors Become Desensitized after Overstimulation<br>Chapter 17 PLASMA PROTEINS<br>Plasma Proteins Are Both Synthesized and Destroyed in the<br>Liver<br>Albumin Prevents Edema<br>Albumin Binds Many Small Molecules<br>Some Plasma Proteins Are Specialized Carriers of Small<br>Deficiency of α1-Antiprotease Causes Lung Emphysema<br>Levels of Plasma Proteins Are Affected by Many Diseases<br>Blood Components Are Used for Transfusions<br>Blood Clotting Must Be Tightly Controlled<br>Platelets Adhere to Exposed Subendothelial Tissue<br>Insoluble Fibrin Is Formed from Soluble Fibrinogen<br>Thrombin Is Derived from Prothrombin<br>Factor X Can Be Activated by the Extrinsic and Intrinsic<br>Pathways<br>Negative Controls Are Necessary to Prevent Thrombosis<br>Plasmin Degrades the Fibrin Clot<br>Heparin and the Vitamin K Antagonists Are Used as<br>Anticoagulants<br>Clotting Factor Deficiencies Cause Abnormal Bleeding<br>Tissue Damage Causes Release of Cellular Enzymes into<br>Blood<br>Serum Enzymes Are Used for the Diagnosis of Many Diseases<br>Chapter 18 Defense Mechanisms<br>Lipophilic Xenobiotics Are Metabolized to Water-soluble Products<br>Cytochrome P-450 Is Involved in Phase I Metabolism<br>Phase II Metabolism Makes Xenobiotics Water-Soluble for Excretion<br>Phase III Metabolism Excretes Xenobiotic Metabolites<br>Drug Metabolizing Enzymes Are Inducible<br>The Innate Immune System Uses Pattern Recognitino Receptors<br>Infection Triggers Inflammation<br>Lymphocytes Possess Antigen Receptors<br>B Lymphocytes Produce Immunoglobulins<br>Antiboidies Consist of Two Light Chains and Two Heavy Chains<br>Different Immunoglobulin Classes Have Different Properties<br>Adaptive Immune Responses Are Based on Clonal Selection<br>Immunoglobulin genes Are Rearranged During B-Cell Development<br>The T-Cell Receptor Recruits Cytosolic Tyrosine Protein Kinases<br>Mediatros of Inflammation Are Produced form Arachidonic Acid<br>Prostaglandins Are Synthesized in All Tissues<br>Prostanoids Participate in Many Physiological Processes<br>Leukotrienes Are Produced by the Lipoxygenase Pathway<br>Anti-Inflammatory Drugs Inhibit the Synthesis of Eicosanoids<br>Chapter 19 CELLULAR GROWTH CONTROL AND CANCER<br>The Cell Cycle Is Controlled at Two Checkpoints<br>Cells Can Be Grown in Culture<br>Cyclins Play Key Roles in Cell Cycle Control<br>Retinoblastoma Protein Guards the G<sub>1</sub> Checkpoint<br>Cell Proliferation Is Triggered by Mitogens<br>Mitogens Regulate Gene Expression<br>Cells Can Commit Suicide<br>Cancers Are Monoclonal in Origin<br>Cancer Is Caused by Activation of Growth-Promoting Genes<br>and Inactivation of Growth-Inhibiting Genes<br>Some Retroviruses Contain an Oncogene<br>Retroviruses Can Cause Cancer by Inserting Themselves Next<br>to a Cellular Proto-Oncogene<br>Many Oncogenes Code for Components of Mitogenic Signaling<br>Cancer Susceptibility Syndromes Are Caused by Inherited<br>Mutations in Tumor Suppressor Genes<br>Many Tumor Suppressor Genes Are Known<br>Components of the Cell Cycle Machinery Are Abnormal in Most<br>Cancers<br>DNA Damage Causes Either Growth Arrest or Apoptosis<br>Most Spontaneous Cancers Are Defective in p53 Action<br>The P13K/Protein Kinase B Pathway Is Activated in Many<br>The Products of Some Viral Oncogenes Neutralize the Products<br>of Cellular Tumor Suppressor Genes<br>Tumors Become More Malignant through Darwinian Selection<br>Intestinal Polyps Are Benign Lesions<br>Intestinal Polyps Can Evolve into Colon Cancer<br><br>Part FIVE METABOLISM<br>Chapter 20 DIGESTIVE ENZYMES<br>Saliva Contains α-Amylase and Lysozyme<br>Protein and Fat Digestion Start in the Stomach<br>The Pancreas Is a Factory for Digestive Enzymes<br>Fat Digestion Requires Bile Salts<br>Some Digestive Enzymes Are Anchored to the Surface of the<br>Microvilli<br>Poorly Digestible Nutrients Cause Flatulence<br>Many Digestive Enzymes Are Released as Inactive<br>Precursors<br>Chapter 21 INTRODUCTION TO METABOLIC PATHWAYS<br>Alternative Substrates Can Be Oxidized in the Body Metabolic Processes Are Compartmentalized<br>Free Energy Changes in Metabolic Pathways Are<br>Additive<br>Most Metabolic Pathways Are Regulated<br>Feedback Inhibition and Feedforward Stimulation Are the Most<br>Important Regulatory Principles<br>Metabolism Is Regulated to Ensure Homeostasis<br>Inherited Enzyme Deficiencies Cause Metabolic Diseases<br>Vitamin Deficiencies, Toxins, and Endocrine Disorders Can Disrupt<br>Metabolic Pathways<br>Chapter 22 GLYCOLYSIS, TRICARBOXYLIC ACID CYCLE, AND OXIDATIVE PHOSPHORYLATION<br>Glucose Uptake into the Cells Is Regulated<br>Glucose Degradation Begins in the Cytoplasm and Ends in the<br>Mitochondria<br>Glycolysis Begins with ATP-Dependent Phosphorylations<br>Most Glycolytic Intermediates Have Three Carbons<br>Phosphofructokinase Is the Most Important Regulated Enzyme<br>of Glycolysis<br>Lactate Is Produced under Anaerobic Conditions<br>Pyruvate Is Decarboxylated to Acetyl-CoA in the<br>The TCA Cycle Produces Two Molecules of Carbon Dioxide for<br>Each Acetyl Residue<br>Reduced Coenzymes Are the Most Important Products of the TCA<br>Cycle<br>Oxidative Pathways Are Regulated by Energy Charge and<br>[NADH]/[NAD<sup>+</sup>] Ratio<br>TCA Cycle Provides an Important Pool of Metabolic<br>Intermediates<br>Antiporters Transport Metabolites across the Inner Mitochondrial<br>Membrane<br>The Respiratory Chain Channels Electrons fromNADH<br>and FADH<sub>2</sub> to Molecular Oxygen<br>Standard Reduction Potential Is the Tendency to Donate<br>Electrons<br>The Respiratory Chain Contains Flavoproteins, Iron-Sulfur<br>Proteins, Cytochromes, Ubiquinone, and Protein-Bound<br>Copper<br>The Respiratory Chain Contains Large Multiprotein<br>Complexes<br>The Respiratory Chain Creates a Proton Gradient<br>The Proton Gradient Drives ATP Synthesis<br>The Efficiency of Glucose Oxidation Is Close to 40%<br>Oxidative Phosphorylation Is Limited by the Supply of<br>ADP<br>Brown Adipose Tissue Contains an Uncoupling Protein<br>Mutations in Mitochondrial DNA Can Cause Disease<br>Chapter 23 Oxygen Deficiency and Oxygen Toxicity<br>Ischemia Leads to Infarction<br>Oxidative Phosphorylation Is Inhibited by Many Poisons<br>Hypoxia Inducible Factor Adjusts Cell Metabolism to Hypoxia<br>Reactive Oxygen Derivatives Are Formed during Oxidative Metabolism<br>The Respiratory Chain Is a Major Source of Superoxide<br>Cells Have Specialized Enzymes to Destroy Reactive Oxygen Species<br>Free Radical Formation Is Affected by Energy Supply and Energy Consumption<br>Some Vitamins and Phytochemicals Can Scavange Free Radicals<br>The NRF2 Transcription Factor Coordinates Defenses against Reactive Oxygen Species<br>Phagocytic Cells Use Reactive Oxygen Species for Intracellular Killing<br>Chapter 24 CARBOHYDRATE METABOLISM<br>An Adequate Blood Glucose Level Must Be Maintained at All<br>Times<br>Gluconeogenesis Bypasses the Three Irreversible Reactions of<br>Glycolysis<br>Fatty Acids Cannot Be Converted into Glucose<br>Glycolysis and Gluconeogenesis Are Regulated by Hormones<br>Glycolysis and Gluconeogenesis Are Fine Tuned by Allosteric<br>Effectors and Hormone-Induced Enzyme<br>Phosphorylations<br>Fructose-2,6-biphosphate Switches the Liver from Gluconeogenesis to Glycolysis<br>Glucokinase Is Regulated by Two Regulatory Proteins<br>Carbohydrate Is Stored as Glycogen<br>Glycogen Is 0Synthesized from Glucose<br>Glycogen Is Degraded by Phosphorolytic Cleavage<br>Glycogen Metabolism Is Regulated by Hormones and<br>Metabolites<br>Glycogen Accumulates in Several Enzyme Deficiencies<br>Fructose Is Channeled into Glycolysis/Gluconeogenesis<br>Excess Fructose Is Problematic<br>Excess Galactose Is Channeled into the Pathways of Glucose<br>The Pentose Phosphate Pathway Supplies NADPH and<br>Ribose-5-Phosphate<br>Fructose Is the Principal Sugar in Seminal Fluid<br>Amino Sugars and Sugar Acids Are Made from Glucose<br>Chapter 25 THE METABOLISM OF FATTY ACIDS AND TRIGLYCERIDES<br>Fatty Acids Differ in Their Chain Length and Number of<br>Double Bonds<br>Chylomicrons Transport Triglycerides from the Intestine to Other<br>Tissues<br>Adipose Tissue Is Specialized for the Storage of Triglycerides<br>Fat Metabolism in Adipose Tissue Is under Hormonal<br>Control<br>Fatty Acids Are Transported into the Mitochondrion<br>β-Oxidation Produces Acetyl-CoA, NADH, and FADH<sub>2</sub><br>Special Fatty Acids Require Special Reactions<br>The Liver Converts Excess Fatty Acids to Ketone Bodies<br>Fatty Acids Are Synthesized from Acetyl-CoA<br>Acetyl-CoA Is Shuttled into the Cytoplasm as Citrate<br>Fatty Acid Synthesis Is Regulated by Hormones and<br>AMP-Activated Protein Kinase Adapts Metabolic Pathways to Cellular Energy Status<br>Most Fatty Acids Can Be Synthesized from Palmitate<br>Fatty Acids Regulate Gene Expression<br>Polyunsaturated Fatty Acids Can Be Oxidized<br>Nonenzymatically<br>Chapter 26 THE METABOLISM OF MEMBRANE LIPIDS<br>Phosphatidic Acid Is an Intermediate in Phosphoglyceride<br>Synthesis<br>Phosphoglycerides Are Remodeled Continuously<br>Sphingolipids Are Synthesized from Ceramide<br>Deficiencies of Sphingolipid-Degrading Enzymes Cause Lipid<br>Storage Diseases<br>Cholesterol Is the Least Soluble Membrane Lipid<br>Cholesterol Is Derived from Both Endogenous Synthesis and the<br>Diet<br>Cholesterol Biosynthesis Is Regulated at the Level of HMG-CoA<br>Reductase<br>Bile Acids Are Synthesized from Cholesterol<br>Bile Acids Are Subject to Extensive Enterohepatic Circulation<br>Most Gallstones Consist of Cholesterol<br>Chapter 27 LIPID TRANSPORT<br>Most Plasma Lipids Are Components of Lipoproteins<br>Lipoproteins Have Characteristic Lipid and Protein<br>Compositions<br>Dietary Lipids Are Transported by Chylomicrons<br>VLDL Is a Precursor of LDL<br>LDL Is Removed by Receptor-Mediated Endocytosis<br>Cholesterol Regulates Its Own Metabolism<br>HDL Is Needed for Reverse Cholesterol Transport<br>Lipoproteins Can Initiate Atherosclerosis<br>Lipoproteins Respond to Diet and Lifestyle<br>Hyperlipoproteinemias Are Grouped into Five Phenotypes<br>Hyperlipidemias Are Treated with Diet and Drugs<br>AMINO ACID METABOLISM<br>Amino Acids Can Be Used for Gluconeogenesis and<br>Ketogenesis<br>The Nitrogen Balance Indicates the Net Rate of Protein<br>The Amino Group of Amino Acids Is Released as Ammonia<br>Ammonia Is Detoxified to Urea<br>Urea Is Synthesized in the Urea Cycle<br>Hyperammonemia Can Be Treated with Diet and Drugs<br>Some Amino Acids Are Closely Related to Common Metabolic<br>Glycine, Serine, and Threonine Are Glucogenic<br>Proline, Arginine, Ornithine, and Histidine Are Degraded to<br>Glutamate<br>Methionine and Cysteine Are Metabolically Related<br>Valine, Leucine, and Isoleucine Are Degraded by Transamination<br>and Oxidative Decarboxylation<br>Phenylalanine and Tyrosine Are Both Glucogenic and<br>Ketogenic<br>Melanin Is Shesized from Tyrosine<br>Lysine and Tryptophan Have Lengthy Catabolic Pathways<br>The Liver Is the Most Important Organ of Amino Acid<br>Glutamine Participates in Renal Acid-Base Regulation<br>Chapter 29 METABOLISM OF IRON AND HEME<br>Iron Is Conserved Very Efficiently in the Body<br>Iron Uptake by Cells Is Regulated<br>Dietary Iron Is Absorbed in the Duodenum<br>Dietary Iron Absorption Is Regulated<br>Iron Deficiency Is the Most Common Micronutrient Deficiency Worldwide<br>Bone Marrow and Liver Are the Most Important Sites of Heme<br>Heme Is Synthesized from Succinyl-Coenzyme A and Glycine<br>Porphyrias Are Caused by Deficiencies of Heme-Synthesizing<br>Enzymes<br>Heme Is Degraded to Bilirubin<br>Bilirubin Is Conjugated and Excreted by the Liver<br>Elevations of Serum Bilirubin Cause Jaundice<br>Many Diseases Can Cause Jaundice<br>Chapter 30 THE METABOLISM OF PURINES AND<br>PYRIMIDINES<br>Purine Synthesis Starts with Ribose-5-Phosphate<br>Purines Are Degraded to Uric Acid<br>Free Purine Bases Can Be Salvaged<br>Pyrimidines Are Synthesized from Carbamoyl Phosphate and<br>Aspartate<br>DNA Synthesis Requires Deoxyribonucleotides<br>Many Antineoplastic Drugs Inhibit Nucleotide Metabolism<br>Uric Acid Has Limited Water Solubility<br>Hyperuricemia Causes Gout<br>Abnormalities of Purine-Metabolizing Enzymes Can Cause<br>Gout<br>Gout Can Be Treated with Drugs<br>Chapter 31 MICRONUTRIENTS<br>Riboflavin Is a Precursor of Flavin Mononucleotide<br>and Flavin Adenine Dinucleotide<br>Niacin Is a Precursor of NAD and NADP<br>Thiamin Deficiency Causes Weakness and Amnesia<br>Vitamin B<sub>6</sub> Plays a Key Role in Amino Acid Metabolism<br>Pantothenic Acid Is a Building Block of Coenzyme A<br>Biotin Is a Coenzyme in Carboxylation Reactions<br>Folic Acid Deficiency Causes Megaloblastic Anemia<br>Vitamin B<sub>12</sub> Requires Intrinsic Factor for Its Absorption<br>Vitamin C Is a Water-Soluble Antioxidant<br>Retinol, Retinal, and Retinoic Acid Are the Active Forms of<br>Vitamin A<br>Vitamin D Is a Prohormone<br>Vitamin E Prevents Lipid Oxidation<br>Many Vitamins and Phytochemicals Are Antioxidants<br>Vitamin K Is Required for Blood Clotting<br>Zinc Is a Constituent of Many Enzymes<br>Copper Participates in Reactions of Molecular Oxygen<br>Some Trace Elements Serve Very Specific Functions<br>Chapter 32 INTEGRATION OF METABOLISM<br>Insulin Is Released in Response to Elevated Glucose<br>Insulin Stimulates the Utilization of Nutrients<br>Protein Synthesis Is Coordinated by the mTOR Complex<br>Glucagon Maintains the Blood Glucose Level<br>Catecholamines Mediate the Flight-or-Fight Response<br>Glucocorticoids Are Released in Chronic Stress<br>Energy Is Expended Continuously<br>Stored Fat and Glycogen Are Degraded between Meals<br>Adipose Tissue Is the Most Important Energy Depot<br>The Liver Converts Dietary Carbohydrates to Glycogen<br>and Fat after a Meal<br>The Liver Maintains the Blood Glucose Level during Fasting<br>Ketone Bodies Provide Lipid-Based Energy during<br>Fasting<br>Obesity Is Common<br>in All Affluent Countries<br>Appetite Control Is the Most Important Determinant of Obesity<br>Obesity Is Related to Insulin Resistance<br>Diabetes Is Caused by Insulin Deficiency or Insulin<br>Resistance<br>In Diabetes, Metabolism Is Regulated as in<br>Starvation<br>Diabetes Is Diagnosed with Laboratory Tests<br>Diabetes Leads to Late Complications<br>Many Drugs Are Available for Diabetes Treatment<br>Contracting Muscle Has Three Energy Sources<br>Catecholamines Coordinate Metabolism during Exercise<br>Physical Exercise Leads to Adaptive Changes<br>Ethanol Is Metabolized to Acetyl-CoA in the Liver<br>Liver Metabolism Is Deranged by Alcohol<br>Alcoholism Leads to Fatty Liver and Liver Cirrhosis<br>Most "Diseases of Civilization" Are Caused by Aberrant<br>Livestyles<br>Aging Is the Greatest Challenge for Medical Research<br>Anti-Aging Treatments Are Being Investigated<br><br>ANSWERS TO QUESTIONS<br>GLOSSARY<br>CREDITS<br>EXTRA ONLINE-ONLY CASE STUDIES {more new Cases to be added, to come}<br>The Mafia Boss<br>Viral Gastroenteritis<br>Death in Installments<br>A Mysterious Death<br>To Treat or Not to Treat?<br>Yellow Eyes<br>An Abdominal Emergency<br>Shortness of Breath<br>Itching<br>Abdominal Pain<br>Rheumatism<br>A Bank Manager in Trouble<br>Kidney Problems<br>Gender Blender<br>Man Overboard!<br>Spongy Bones<br>Blisters<br>The Sunburned Child<br>Too Much Ammonia<br>ANSWERS TO CASE STUDIES