Principles of Medical Biochemistry

Dr. Meisenberg emailed us Jan. 24, 2019 to note his updated email address meisenberggerhard@gmail.com since he has now officially retired from his university position.

• Part ONEPRINCIPLES OF MOLECULAR STRUCTURE ANDFUNCTION 1Chapter 1INTRODUCTION 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 NoncovalentInteractions Triglycerides Consist of Fatty Acids and Glycerol Monosaccharides Are Polyalcohols with a Keto Group or anAldehyde 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 2INTRODUCTION TO PROTEIN STRUCTURE Amino Acids Are Zwitterions Amino Acid Side Chains Form Many NoncovalentInteractions Peptide Bonds and Disulfide Bonds Form the Primary Structure ofProteins Proteins Can Fold Themselves into Many Shapes ?-Helix and ?-Pleated Sheet Are the Most Common SecondaryStructures in Proteins Globular Proteins Have a Hydrophobic Core Proteins Lose Their Biological Activities When Their Higher-OrderStructure Is Destroyed The Solubility of Proteins Depends on pH and SaltConcentration Proteins Absorb Ultraviolet Radiation Proteins Can Be Separated by Their Charge or Their MolecularWeight Abnormal Protein Aggregates Can Cause Disease Neurodegenerative Diseases Are Caused by Protein Aggregates Protein Misfolding Can Be Contagious SummaryChapter 3OXYGEN TRANSPORTERS: HEMOGLOBIN ANDMYOGLOBIN The Heme Group Is the Oxygen-Binding Site of Hemoglobin andMyoglobin 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 DifferentQuaternary Structures Oxygen Binding to Hemoglobin Is Cooperative 2,3-Bisphosphoglycerate Is a Negative Allosteric Effector ofOxygen Binding to Hemoglobin Fetal Hemoglobin Has a Higher Oxygen-Binding Affinity thanDoes Adult Hemoglobin The Bohr Effect Facilitates Oxygen Delivery Most Carbon Dioxide Is Transported as Bicarbonate Summary 38Chapter 4ENZYMATIC REACTIONS 39The Equilibrium Constant Describes the Equilibrium of theReaction The Free Energy Change Is the Driving Force for ChemicalReactions The Standard Free Energy Change Determines the Equilibrium Enzymes Are Both Powerful and Selective The Substrate Must Bind to Its Enzyme before the Reaction CanProceed Rate Constants Are Useful for Describing Reaction Rates Enzymes Decrease the Free Energy of Activation Many Enzymatic Reactions Can Be Described by Michaelis-MentenKinetics Km and Vmax Can Be Determined Graphically Substrate Half-Life Can Be Determined for First-Order but NotZero-Order Reactions Kcat/Km Predicts the Enzyme Activity at Low SubstrateConcentration Allosteric Enzymes Do Not Conform to Michaelis-MentenKinetics Enzyme Activity Depends on Temperature and pH Different Types of Reversible Enzyme Inhibition Can BeDistinguished Kinetically Enzymes Stabilize the Transition State Chymotrypsin Forms a Transient Covalent Bond duringCatalysis Summary Chapter 5COENZYMES 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 TWOGENETIC INFORMATION: DNA, RNA, ANDPROTEIN SYNTHESIS Chapter 6DNA, 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 DenaturedDNA 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 theDNA 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' Terminusof the tRNA Many Transfer RNAs Recognize More than One Codon Ribosomes Are the Workbenches for Protein Synthesis The Initiation Complex Brings Together Ribosome, MessengerRNA, and Initiator tRNA Polypeptides Grow Stepwise from the Amino Terminus to theCarboxyl Terminus Protein Synthesis Is Energetically Expensive Gene Expression Is Tightly Regulated A Repressor Protein Regulates Transcription of the lac Operonin E. coli Anabolic Operons Are Repressed by the End Product of thePathway Glucose Regulates the Transcription of Many CatabolicOperons Transcriptional Regulation Depends on DNA-BindingProteins Summary Chapter 7THE HUMAN GENOME Chromatin Consists of DNA and Histones The Nucleosome Is the Structural Unit of Chromatin Covalent Histone Modifications Regulate DNA Replication andTranscription DNA Methylation Silences Genes All Eukaryotic Chromosomes Have a Centromere, Telomeres, andReplication Origins Telomerase Is Required (but Not Sufficient) for Immortality Eukaryotic DNA Replication Requires Three DNAPolymerases 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 ReverseTranscriptase Mobile Elements Are Dangerous Humans Have Approximately 20,000 Genes Transcriptional Initiation Requires General TranscriptionFactors 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 NumberVariations Summary Chapter 8PROTEIN TARGETING AND PROTEOSTASISA Signal Sequence Directs Polypeptides to the EndoplasmicReticulum 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 9INTRODUCTION 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-ChainGene SA Heterozygotes Are Protected from Tropical Malaria ?-Thalassemia Is Most Often Caused by Large DeletionsMany Different Mutations Can Cause ?-Thalassemia Fetal Hemoglobin Protects from the Effects of ?-Thalassemia andSickle Cell Disease Summary Chapter 10VIRUSES Viruses Can Replicate Only in a Host Cell Bacteriophage T4 Destroys Its Host Cell DNA Viruses Substitute Their Own DNA for the Host CellDNA ? Phage Can Integrate Its DNA into the Host CellChromosome RNA Viruses Require an RNA-Dependent RNA Polymerase Retroviruses Replicate Through a DNA Intermediate Plasmids Are Small "Accessory Chromosomes" or "SymbioticViruses" of Bacteria Bacteria Can Exchange Genes by Transformation andTransduction Jumping Genes Can Change Their Position in the Genome Summary Chapter 11DNA TECHNOLOGY Restriction Endonucleases Cut Large DNA Molecules into SmallerFragments Large Probes Are Used to Detect Copy Number Variations Small Probes Are Used to Detect Point Mutations Southern Blotting Determines the Size of RestrictionFragments DNA Can Be Amplified with the Polymerase Chain Reaction PCR Is Used for Preimplantation Genetic Diagnosis Allelic Heterogeneity Is the Greatest Challenge for MolecularGenetic 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-EfficientWhole-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 RogueGenes Genes Can Be Altered in Animals Tissue-Specific Gene Expression Can Be Engineered intoAnimals Human Germline Genome Editing is Technically Possible Summary Part THREECELL AND TISSUE STRUCTURE Chapter 12BIOLOGICAL 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 MembraneProteins Membranes Are Asymmetrical Membranes Are Fragile Membrane Proteins Carry Solutes across the Lipid Bilayer Transport against an Electrochemical Gradient Requires MetabolicEnergy Active Transport Consumes ATP Sodium Cotransport Brings Molecules into the Cell Summary Chapter 13THE CYTOSKELETON The Erythrocyte Membrane Is Reinforced by a SpectrinNetwork 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 ExtracellularMatrix Microtubules Consist of Tubulin Eukaryotic Cilia and Flagella Contain a 9 + 2 Array ofMicrotubules Cells Form Specialized Junctions with Other Cells and with theExtracellular Matrix Summary Chapter 14THE EXTRACELLULAR MATRIX Collagen Is the Most Abundant Protein in the Human BodyTropocollagen Molecule Forms a Long Triple Helix Collagen Fibrils Are Staggered Arrays of TropocollagenMolecules Collagen Is Subject to Extensive Posttranslational Processing Collagen Metabolism Is Altered in Aging and Disease Many Genetic Defects of Collagen Structure and Biosynthesis AreKnown Elastic Fibers Contain Elastin and Fibrillin The Amorphous Ground Substance Contains Hyaluronic Acid Sulfated Glycosaminoglycans Are Covalently Bound to CoreProteins Cartilage Contains Large Proteoglycan Aggregates Proteoglycans Are Synthesized in the ER and Degraded inLysosomes Mucopolysaccharidoses Are Caused by Deficiency ofGlycosaminoglycan-Degrading Enzymes Bone Consists of Calcium Phosphates in a CollagenousMatrix Basement Membranes Contain Type IV Collagen, Laminin,and Heparan Sulfate Proteoglycans Fibronectin Glues Cells and Collagen Fibers Together SummaryPart FOURMOLECULAR PHYSIOLOGY Chapter 15EXTRACELLULAR MESSENGERS Steroid Hormones Are Made from Cholesterol Progestins Are the Biosynthetic Precursors of All Other SteroidHormones Thyroid Hormones Are Synthesized from Protein-BoundTyrosine T4 Becomes Activiated to T3 in the Target Tissues Both Hypothyroidism and Hyperthyroidism Are CommonDisorders 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 NeuromuscularJunction There Are Many Neurotransmitters Summary Chapter 16INTRACELLULAR 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-SpecificProtein Kinases Growth Factors and Insulin Trigger Multiple SignalingCascades Cytokin Receptors Use the JAK-Stat Pathway Many Receptors Become Desensitized after Overstimulation Summary Chapter 17PLASMA PROTEINS The Blood pH Is Tightly Regulated Acidosis and Alkalosis Are Common in Clinical Practice Plasma Proteins Are Both Synthesized and Destroyed in theLiver Albumin Prevents Edema Albumin Binds Many Small Molecules Some Plasma Proteins Are Specialized Carriers of SmallMolecules 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 IntrinsicPathways Negative Controls Are Necessary to Prevent Thrombosis Plasmin Degrades the Fibrin Clot Heparin and the Vitamin K Antagonists Are Used asAnticoagulants Clotting Factor Deficiencies Cause Abnormal Bleeding Tissue Damage Causes Release of Cellular Enzymes intoBlood Serum Enzymes Are Used for the Diagnosis of Many Diseases Summary Chapter 18Defense Mechanisms Lipophilic Xenobiotics Are Metabolized to Water-soluble Products Cytochrome P-450 Is Involved in Phase I MetabolismPhase II Metabolism Makes Xenobiotics Water-Soluble for ExcretionPhase 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 AcidProstaglandins 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 EicosanoidsSummary Chapter 19CELLULAR 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 Genesand Inactivation of Growth-Inhibiting Genes Some Retroviruses Contain an Oncogene Retroviruses Can Cause Cancer by Inserting Themselves Nextto a Cellular Proto-Oncogene Many Oncogenes Code for Components of Mitogenic SignalingCascades Cancer Susceptibility Syndromes Are Caused by InheritedMutations in Tumor Suppressor Genes Many Tumor Suppressor Genes Are Known Components of the Cell Cycle Machinery Are Abnormal in MostCancers 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 ManyCancers The Products of Some Viral Oncogenes Neutralize the Productsof 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 FIVEMETABOLISM Chapter 20DIGESTIVE 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 theMicrovilli Poorly Digestible Nutrients Cause Flatulence Many Digestive Enzymes Are Released as InactivePrecursors Summary Chapter 21INTRODUCTION 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 MostImportant Regulatory Principles Metabolism Is Regulated to Ensure Homeostasis Inherited Enzyme Deficiencies Cause Metabolic Diseases Vitamin Deficiencies, Toxins, and Endocrine Disorders Can DisruptMetabolic Pathways Summary Chapter 22GLYCOLYSIS, TRICARBOXYLIC ACID CYCLE, ANDOXIDATIVE PHOSPHORYLATION Glucose Uptake into the Cells Is Regulated Glucose Degradation Begins in the Cytoplasm and Ends in theMitochondria Glycolysis Begins with ATP-Dependent Phosphorylations Most Glycolytic Intermediates Have Three Carbons Phosphofructokinase Is the Most Important Regulated Enzymeof Glycolysis Lactate Is Produced under Anaerobic Conditions Pyruvate Is Decarboxylated to Acetyl-CoA in theMitochondria The TCA Cycle Produces Two Molecules of Carbon Dioxide forEach Acetyl Residue Reduced Coenzymes Are the Most Important Products of the TCACycle Oxidative Pathways Are Regulated by Energy Charge and[NADH]/[NAD+] Ratio TCA Cycle Provides an Important Pool of MetabolicIntermediates Antiporters Transport Metabolites across the Inner MitochondrialMembrane The Respiratory Chain Channels Electrons fromNADHand FADH2 to Molecular Oxygen Standard Reduction Potential Is the Tendency to DonateElectrons The Respiratory Chain Contains Flavoproteins, Iron-SulfurProteins, Cytochromes, Ubiquinone, and Protein-BoundCopper The Respiratory Chain Contains Large MultiproteinComplexes 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 ofADP Brown Adipose Tissue Contains an Uncoupling Protein Mutations in Mitochondrial DNA Can Cause Disease Summary Chapter 23Oxygen 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 24CARBOHYDRATE METABOLISM An Adequate Blood Glucose Level Must Be Maintained at AllTimes Gluconeogenesis Bypasses the Three Irreversible Reactions ofGlycolysis Fatty Acids Cannot Be Converted into Glucose Glycolysis and Gluconeogenesis Are Regulated by Hormones Glycolysis and Gluconeogenesis Are Fine Tuned by AllostericEffectors and Hormone-Induced EnzymePhosphorylations 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 andMetabolites Glycogen Accumulates in Several Enzyme Deficiencies Fructose Is Channeled into Glycolysis/Gluconeogenesis Excess Fructose Is ProblematicExcess Galactose Is Channeled into the Pathways of GlucoseMetabolism The Pentose Phosphate Pathway Supplies NADPH andRibose-5-Phosphate Fructose Is the Principal Sugar in Seminal Fluid Amino Sugars and Sugar Acids Are Made from Glucose Summary Chapter 25THE METABOLISM OF FATTY ACIDS ANDTRIGLYCERIDES Fatty Acids Differ in Their Chain Length and Number ofDouble Bonds Chylomicrons Transport Triglycerides from the Intestine to OtherTissues Adipose Tissue Is Specialized for the Storage of Triglycerides Fat Metabolism in Adipose Tissue Is under HormonalControl 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 andMetabolites 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 OxidizedNonenzymaticallySummary Chapter 26THE METABOLISM OF MEMBRANE LIPIDS 000Phosphatidic Acid Is an Intermediate in PhosphoglycerideSynthesis Phosphoglycerides Are Remodeled Continuously Sphingolipids Are Synthesized from Ceramide Deficiencies of Sphingolipid-Degrading Enzymes Cause LipidStorage Diseases Cholesterol Is the Least Soluble Membrane Lipid Cholesterol Is Derived from Both Endogenous Synthesis and theDiet Cholesterol Biosynthesis Is Regulated at the Level of HMG-CoAReductase Bile Acids Are Synthesized from Cholesterol Bile Acids Are Subject to Extensive Enterohepatic Circulation Most Gallstones Consist of Cholesterol Summary Chapter 27LIPID TRANSPORT Most Plasma Lipids Are Components of Lipoproteins Lipoproteins Have Characteristic Lipid and ProteinCompositions 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 DrugsSummary Chapter 26AMINO ACID METABOLISM Amino Acids Can Be Used for Gluconeogenesis andKetogenesis The Nitrogen Balance Indicates the Net Rate of ProteinSynthesis 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 MetabolicIntermediates Glycine, Serine, and Threonine Are Glucogenic Proline, Arginine, Ornithine, and Histidine Are Degraded toGlutamate Methionine and Cysteine Are Metabolically Related Valine, Leucine, and Isoleucine Are Degraded by Transaminationand Oxidative Decarboxylation Phenylalanine and Tyrosine Are Both Glucogenic andKetogenicMelanin Is Shesized from Tyrosine Lysine and Tryptophan Have Lengthy Catabolic Pathways The Liver Is the Most Important Organ of Amino AcidMetabolism Glutamine Participates in Renal Acid-Base Regulation Summary Chapter 29METABOLISM OF IRON AND HEMEIron 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 HemeSynthesis Heme Is Synthesized from Succinyl-Coenzyme A and Glycine Porphyrias Are Caused by Deficiencies of Heme-SynthesizingEnzymes 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 30THE METABOLISM OF PURINES ANDPYRIMIDINES 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 andAspartate 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 CauseGout Gout Can Be Treated with Drugs Summary Chapter 31MICRONUTRIENTS Riboflavin Is a Precursor of Flavin Mononucleotideand 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 ofVitamin 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 EnzymesCopper Participates in Reactions of Molecular Oxygen Some Trace Elements Serve Very Specific Functions Summary Chapter 32INTEGRATION 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 Glycogenand Fat after a Meal The Liver Maintains the Blood Glucose Level during Fasting Ketone Bodies Provide Lipid-Based Energy duringFasting 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 InsulinResistance In Diabetes, Metabolism Is Regulated as inStarvation 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 AberrantLivestyles Aging Is the Greatest Challenge for Medical ResearchAnti-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 BossViral GastroenteritisDeath in InstallmentsA Mysterious DeathTo Treat or Not to Treat?Yellow EyesAn Abdominal EmergencyShortness of BreathItchingAbdominal PainRheumatismA Bank Manager in TroubleKidney ProblemsGender BlenderMan Overboard!Spongy BonesBlistersThe Sunburned ChildToo Much AmmoniaANSWERS TO CASE STUDIES