Principles of Medical Biochemistry; with STUDENT CONSULT Access

by Meisenberg & Simmons

• ISBN13: 9780323029421
• ISBN10: 0323029426
• Edition: 2nd
• Format: Paperback
• Copyright: 2006-01-27
• Publisher: HARCOURT HEALTH SCIENCES-MOSBY

Summary

The smart way to study! Elsevier titles with STUDENT CONSULT will help you master difficult concepts and study more efficiently in print and online! Perform rapid searches. Integrate bonus content from other disciplines. Download text to your handheld device. And a lot more. Each STUDENT CONSULT title comes with full text online, a unique image library, case studies, USMLE style questions, and online note-taking to enhance your learning experience. Half the size and weight of the usual biochemistry text. Includes clinical cases throughout the text, and a case study section at the end in order to illustrate the practical application of biochemistry concepts. Comprehensive coverage of all the topics that are typically included in medical biochemistry courses Focuses on topics that are of specific medical interest, such as plasma proteins and lipoproteins, molecular carcinogenesis, laboratory diagnostic tests, and the rapidly evolving new applications of molecular genetics. Expanded coverage of molecular genetics, genome structure, and the molecular basis of genetic disease. Discussions of gene therapy and germline gene modifications. Information on molecular carcinogenesis, apoptosis, and signaling pathways. Superb new page design with full color illustrations Online version via the STUDENT CONSULT website with USMLE test questions and integration links

Table of Contents

PART ONE PRINCIPLES OF MOLECULAR STRUCTURE AND FUNCTION	1	(68)
Introduction to Biomolecules	3	(16)
Water Is the Solvent of Life	3	(1)
Water Contains Hydronium Ions and Hydroxyl Ions	4	(1)
Ionizable Groups Are Characterized by Their pK Values	5	(1)
Bonds Are Formed by Reactions between Functional Groups	6	(1)
Isomeric Forms Are Common in Biomolecules	7	(1)
The Properties of Biomolecules Are Determined by Their Noncovalent Interactions	8	(2)
Triglycerides Consist of Fatty Acids and Glycerol	10	(1)
Monosaccharides Are Polyalcohols with a Keto Group or an Aldehyde Group	11	(1)
Monosaccharides Form Ring Structures	12	(1)
Complex Carbohydrates Are Formed by Glycosidic Bonds	12	(1)
Polypeptides Are Formed from Amino Acids	13	(2)
Nucleic Acids Are Formed from Nucleotides	15	(1)
Most Biomolecules Are Polymers	15	(4)
Summary	17	(2)
Introduction to Protein Structure	19	(14)
Amino Acids Are Zwitterions	19	(1)
Amino Acid Side Chains Form Many Noncovalent Interactions	20	(2)
Peptide Bonds and Disulfide Bonds Form the Primary Structure of Proteins	22	(1)
Proteins Can Fold Themselves into Many Different Shapes	23	(2)
The α Helix and β-Pleated Sheet Are the Most Common Secondary Structures in Proteins	25	(1)
Globular Proteins Have a Hydrophobic Core	26	(1)
The Higher Order Structure Forms While the Polypeptide Is Being Synthesized	26	(1)
Proteins Lose Their Biological Activities When Their Higher Order Structure Is Destroyed	27	(1)
The Solubility of Proteins Depends on pH and Salt Concentration	28	(1)
Proteins Absorb Ultraviolet Radiation	28	(1)
Proteins Can Be Separated by Their Charge or Their Molecular Weight	28	(5)
Summary	30	(3)
Oxygen Transporters: Hemoglobin and Myoglobin	33	(10)
The Heme Group Is the Oxygen-Binding Site of Hemoglobin and Myoglobin	33	(1)
Myoglobin Is a Tightly Packed Globular Protein	34	(1)
The Red Blood Cells Are Specialized for Oxygen Transport	34	(1)
The Hemoglobins Are Tetrameric Proteins	35	(1)
Oxygenated and Deoxygenated Hemoglobin Have Different Quaternary Structures	36	(1)
Oxygen Binding to Hemoglobin Is Cooperative	36	(1)
2,3-Bisphosphoglycerate Is a Negative Allosteric Effector of Oxygen Binding to Hemoglobin	37	(1)
Fetal Hemoglobin Has a Higher Oxygen Binding Affinity than Does Adult Hemoglobin	38	(1)
The Bohr Effect Facilitates Oxygen Delivery	38	(1)
Most Carbon Dioxide Is Transported as Bicarbonate	39	(1)
Anemia Is Commonly Seen in Clinical Practice	39	(1)
Methemoglobin Is a Nonfunctional Oxidized Form of Hemoglobin	40	(1)
Carbon Monoxide Competes with Oxygen for Binding to the Heme Iron	40	(3)
Summary	41	(2)
Enzymatic Reactions	43	(18)
The Equilibrium Constant Describes the Equilibrium of the Reaction	43	(1)
The Free Energy Change Is the Driving Force for Chemical Reactions	44	(1)
The Standard Free Energy Change Determines the Equilibrium	45	(1)
Enzymes Are Both Powerful and Selective	46	(1)
The Substrate Must Bind to Its Enzyme before the Reaction Can Proceed	46	(1)
Rate Constants Are Useful for Describing Reaction Rates	47	(1)
Enzymes Decrease the Free Energy of Activation	48	(1)
Many Enzymatic Reactions Can Be Described by Michaelis-Menten Kinetics	48	(2)
Km and Vmax Can Be Determined Graphically	50	(1)
Substrate Half-Life Can Be Determined for First-Order but Not Zero-Order Reactions	51	(1)
Kcat/Km Predicts the Enzyme Activity at Low Substrate Concentration	51	(1)
Allosteric Enzymes Do Not Conform to Michaelis-Menten Kinetics	52	(1)
Enzyme Activity Depends on Temperature and pH	52	(1)
Different Types of Reversible Enzyme Inhibition Can Be Distinguished Kinetically	53	(1)
Covalent Modification Can Inhibit Enzymes Irreversibly	54	(1)
Enzymes Are Classified According to Their Reaction Type	55	(1)
Enzymes Stabilize the Transition State	56	(1)
Chymotrypsin Forms a Transient Covalent Bond during Catalysis	57	(4)
Summary	57	(4)
Coenzymes	61	(8)
ATP Has Two Energy-Rich Bonds	61	(2)
ATP Is the Phosphate Donor in Phosphorylation Reactions	63	(1)
ATP Hydrolysis Drives Endergonic Reactions	63	(1)
Cells Always Try to Maintain a High Energy Charge	64	(1)
Dehydrogenase Reactions Require Specialized Coenzymes	64	(1)
Coenzyme A Activates Organic Acids	64	(1)
S-Adenosyl Methionine Donates Methyl Groups	65	(2)
Many Enzymes Require a Metal Ion	67	(2)
Summary	68	(1)
PART TWO GENETIC INFORMATION: DNA, RNA, AND PROTEIN SYNTHESIS	69	(128)
DNA, RNA, and Protein Synthesis	71	(32)
All Living Organisms Use DNA as Their Genetic Databank	71	(1)
DNA Contains Four Bases	72	(1)
DNA Forms a Double Helix	73	(1)
DNA Can Be Denatured	74	(1)
DNA Is Supercoiled	75	(1)
DNA Replication Is Semiconservative	76	(1)
DNA Is Synthesized by DNA Polymerases	77	(1)
Bacterial DNA Polymerases Have Exonuclease Activities	78	(2)
Unwinding Proteins Present a Single-Stranded Template to the DNA Polymerases	80	(1)
One of the New DNA Strands Is Synthesized Discontinuously	80	(2)
RNA Plays Key Roles in Gene Expression	82	(1)
The σ Subunit Recognizes Promoters	83	(1)
DNA Is Faithfully Copied Into RNA	84	(1)
Transcription Is Terminated When the RNA Forms a Hairpin Loop	84	(1)
Transcription Can Be Inhibited by Drugs	84	(2)
Some RNAs Are Chemically Modified after Transcription	86	(1)
The Genetic Code Defines the Relationship between the Base Sequence of the Messenger RNA and the Amino Acid Sequence of the Polypeptide	87	(2)
Transfer RNA Is the Adapter Molecule in Protein Synthesis	89	(1)
Amino Acids Are Activated by an Ester Bond with the 3'-Terminus of the Transfer RNA	89	(1)
Many Transfer RNAs Recognize More than One Codon	90	(1)
Ribosomes Are the Workbenches for Protein Synthesis	91	(2)
The Initiation Complex Brings Ribosome, Messenger RNA, and Initiator-Transfer RNA Together	93	(1)
Polypeptides Grow Stepwise from the Amino Terminus to the Carboxyl Terminus	94	(1)
Protein Synthesis Is Energetically Expensive	94	(1)
Many Antibiotics Inhibit Protein Synthesis	94	(2)
Gene Expression Is Tightly Regulated	96	(1)
A Repressor Protein Regulates the Transcription of the lac Operon in Escherichia coli	97	(1)
Anabolic Operons Are Repressed by the End Product of the Pathway	98	(1)
Glucose Regulates the Transcription of Many Catabolic Operons	98	(1)
Transcriptional Regulation Depends on DNA-Binding Proteins	99	(4)
Summary	101	(2)
Viruses	103	(16)
Viruses Can Replicate Only in a Host Cell	103	(1)
Bacteriophage T4 Destroys Its Host Cell	103	(1)
DNA Viruses Substitute Their Own DNA for the Host Cell DNA	104	(1)
λ Phage Can Integrate Its DNA into the Host Cell Chromosome	105	(3)
RNA Viruses Require an RNA-Dependent RNA Polymerase	108	(1)
Retroviruses Replicate through a DNA Intermediate	108	(3)
Plasmids Are Small ``Accessory Chromosomes'' or ``Symbiotic Viruses'' of Bacteria	111	(1)
Some Plasmids Are Transmissible	111	(2)
Bacteria Can Exchange Genes by Transformation and Transduction	113	(1)
Jumping Genes Can Change Their Position in the Genome	113	(2)
Genetic Recombination Requires the Cutting and Joining of DNA	115	(4)
Summary	117	(2)
The Human Genome	119	(24)
Chromatin Consists of DNA and Histones	119	(1)
The Nucleosome Is the Structural Unit of Chromatin	119	(1)
Chromatin Structure Is Regulated by Covalent Modifications of Histones and DNA	120	(1)
All Eukaryotic Chromosomes Have a Centromere, Telomeres, and Replication Origins	120	(2)
Telomerase Is Required (but Not Sufficient) for Immortality	122	(2)
Eukaryotic DNA Replication Starts from Many Origins	124	(1)
Most Human DNA Does Not Code for Proteins	124	(2)
Gene Families Originate by Gene Duplication	126	(1)
The Genome Contains Many Tandem Repeats	126	(1)
Microsatellite Expansions Can Cause Disease	127	(1)
Some DNA Sequences Are Copies of Functional RNAs	127	(1)
Some Repetitive DNA Sequences Are Mobile	128	(1)
L1 Elements Encode a Reverse Transcriptase	129	(1)
Alu Sequences Spread with the Help of Reverse Transcriptase from Other Mobile Elements	129	(1)
Humans Have Approximately 30,000 Genes	130	(1)
Eukaryotes Have Three Nuclear RNA Polymerases	131	(1)
Transcriptional Initiation Requires General Transcription Factors	131	(1)
Transcriptional Activator and Repressor Proteins Are Essential for Regulated Gene Expression	131	(1)
Regulatory Sites on the DNA Can Be at Great Distance from the Transcriptional Start Site	132	(2)
Gene Expression Is Regulated by DNA-Binding Proteins	134	(1)
Genes Can Be Silenced by Methylation	135	(1)
Eukaryotic Messenger RNA Is Extensively Processed by Nuclear Enzyme Systems	136	(1)
The Pre-Messenger RNA Is Processed during Transcription	136	(2)
Translation Is Similar in Prokaryotes and Eukaryotes	138	(1)
Messenger RNA Processing and Translation Are Often Regulated	138	(2)
Diphtheria Toxin Inhibits Protein Synthesis	140	(1)
Mitochondria Have Their Own DNA	141	(2)
Summary	142	(1)
Protein Targeting	143	(10)
A Signal Sequence Directs Polypeptides to the Endoplasmic Reticulum	143	(2)
Glycoproteins Are Processed in the Secretory Pathway	145	(3)
Lysosomes Are Derivatives of the Secretory Pathway	148	(1)
Nuclear Proteins Possess Their Own Targeting Sequences	148	(1)
The Endocytic Pathway Brings Proteins into the Cell	148	(2)
Endocytosis Is Regulated by Cytoplasmic Proteins	150	(1)
The Secretory and Endocytic Organelles Are Derived from the Plasma Membrane	150	(1)
Ubiquitin Marks Cellular Proteins for Destruction	151	(1)
The Proteasome Degrades Ubiquitinated Proteins	151	(2)
Summary	152	(1)
Introduction to Genetic Diseases	153	(16)
Mutations Are an Important Cause of Poor Health	153	(1)
There Are Four Types of Genetic Disease	153	(1)
A Change in the Base Sequence of DNA Can Change the Amino Acid Sequence of the Encoded Polypeptide	154	(1)
Mutations Can Be Induced by Radiation and Chemicals	155	(1)
Mismatch Repair Is Coupled to DNA Replication	156	(2)
Damaged DNA Can Be Repaired	158	(1)
Base Excision Repair Removes Abnormal Bases	158	(1)
Nucleotide Excision Repair Removes Bulky Lesions	159	(1)
The Repair of DNA Double-Strand Breaks Is Difficult	159	(1)
Many Genes Are Not Essential for Life	160	(2)
Hemoglobin Genes Are Present in Two Gene Clusters	162	(1)
Many Point Mutations in Hemoglobin Genes Are Known	163	(1)
Sickle Cell Disease Is Caused by a Point Mutation in the β-Chain Gene	163	(2)
SA Heterozygotes Are Protected from Tropical Malaria	165	(1)
The Thalassemias Are Caused by Reduced α or β-Chain Production	165	(1)
α-Thalassemia Is Most Often Caused by Large Deletions	166	(1)
Many Different Mutations Can Cause β-Thalassemia	166	(1)
High Levels of Fetal Hemoglobin Protect from the Effects of β-Thalassemia and Sickle Cell Disease	167	(2)
Summary	167	(2)
DNA Technology	169	(28)
Restriction Endonucleases Cut Large DNA Molecules into Smaller Fragments	169	(1)
DNA Is Sequenced by Controlled Chain Termination	169	(1)
Complementary DNA Probes Are Used for In Situ Hybridization	170	(1)
Dot Blotting Is Used for Genetic Screening	171	(1)
The Size of Restriction Fragments Is Determined by Southern Blotting	172	(1)
DNA Can Be Amplified with the Polymerase Chain Reaction	173	(1)
Polymerase Chain Reaction with Nested Primers Is Used for Preimplantation Genetic Diagnosis	174	(2)
Polymerase Chain Reaction Can Be Used for Deletion Scanning	176	(1)
Allele-Specific Polymerase Chain Reaction Can Detect Point Mutations	177	(1)
Allelic Heterogeneity Is the Greatest Challenge for Molecular Genetic Diagnosis	177	(1)
Single-Nucleotide Polymorphisms, Restriction-Site Polymorphisms, and Variable Number of Tandem Repeats Are Used as Genetic Markers	178	(2)
Tandem Repeats Are Used for DNA Fingerprinting	180	(1)
DNA Microarrays Can Be Used for Genetic Screening	181	(1)
DNA Microarrays Are Used for the Study of Gene Expression	182	(1)
Genomic DNA Fragments Can Be Propagated in Bacterial Plasmids	183	(2)
Complementary DNA Libraries Contain Only Expressed DNA	185	(1)
Expression Vectors Are Used to Manufacture Useful Proteins	186	(1)
The Structure-Function Relationships of Proteins Can Be Determined by Site-Directed Mutagenesis	186	(1)
Gene Therapy Targets Somatic Cells	186	(2)
Viruses Are Used as Vectors for Gene Therapy	188	(1)
Retroviruses Can Splice a Transgene into the Cell's Genome	188	(2)
Antisense Oligonucleotides Can Block the Expression of Rogue Genes	190	(1)
Selective Germline Mutations Can Be Produced	191	(1)
Tissue-Specific Gene Expression Can Be Engineered into Animals	191	(1)
The Production of Transgenic Humans Is Technically Possible	192	(5)
Summary	194	(3)
PART THREE CELL AND TISSUE STRUCTURE	197	(56)
Biological Membranes	199	(18)
Membranes Consist of Lipid and Protein	199	(1)
The Phosphoglycerides Are the Most Abundant Membrane Lipids	199	(1)
Dipalmitoyl-Phosphatidylcholine Is the Most Important Component of Lung Surfactant	200	(2)
Most Sphingolipids Are Glycolipids	202	(1)
Cholesterol Is the Most Hydrophobic Membrane Lipid	203	(1)
Membrane Lipids Form a Bilayer	203	(1)
The Lipid Bilayer Is a Two-Dimensional Fluid	203	(2)
The Lipid Bilayer Is a Diffusion Barrier	205	(1)
Membranes Contain Integral and Peripheral Membrane Proteins	206	(1)
Membranes Are Asymmetrical	206	(2)
Cell Surfaces Have a Fluffy Carbohydrate Coat	208	(1)
Membranes Are Fragile	208	(1)
Membrane Carriers Form Channels across the Lipid Bilayer	209	(2)
Carrier-Mediated Transport Is Substrate-Specific and Saturable and Can Be Selectively Inhibited	211	(1)
Transport against an Electrochemical Gradient Requires Metabolic Energy	211	(1)
Active Transport Consumes Adenosine Triphosphate	212	(1)
Many Molecules Are Transported into the Cell by Sodium Cotransport	212	(1)
The Sodium-Potassium Pump Is Inhibited by Cardiotonic Steroids	212	(5)
Summary	214	(3)
The Cytoskeleton	217	(16)
The Erythrocyte Membrane Is Reinforced by a Spectrin Network	217	(1)
Defects of the Erythrocyte Membrane Skeleton Cause Hemolytic Anemia	217	(1)
Muscular Dystrophies Are Caused by Defects in Structural Proteins of Skeletal Muscle	218	(2)
The Keratins Are the Most Important Structural Proteins of Epithelial Tissues	220	(2)
Abnormalities of Keratin Structure Cause Skin Diseases	222	(1)
Actin Filaments Are Formed from Globular Subunits	222	(1)
Striated Muscle Contains Thick and Thin Filaments	223	(1)
Myosin Is a Two-Headed Molecule with ATPase Activity	223	(3)
Muscle Contraction Requires Calcium and ATP	226	(1)
Microtubules Consist of Tubulin	227	(1)
Eukaryotic Cilia and Flagella Contain a 9 + 2 Array of Microtubules	227	(1)
Structural Defects of Cilia and Flagella Cause Bronchitis, Sinusitis, and Infertility	228	(1)
Cells Form Specialized Junctions with Other Cells and with the Extracellular Matrix	228	(5)
Summary	230	(3)
The Extracellular Matrix	233	(20)
Collagen Is the Most Abundant Protein in the Human Body	233	(1)
The Tropocollagen Molecule Forms a Long Triple Helix	234	(1)
Collagen Fibrils Are Staggered Arrays of Tropocollagen Molecules	235	(1)
Collagen Is Subject to Extensive Post-translational Processing	236	(1)
Collagen Genes Have Unusual Structures	237	(1)
Collagen Metabolism Is Altered in Aging and Disease	238	(1)
Many Genetic Defects of Collagen Structure and Biosynthesis Are Known	239	(1)
Elastic Fibers Contain Elastin and Fibrillin	240	(1)
Hyaluronic Acid Is a Component of the Amorphous Ground Substance	241	(1)
Sulfated Glycosaminoglycans Are Covalently Bound to Core Proteins	242	(1)
Cartilage Contains Large Proteoglycan Aggregates	243	(1)
Bone Consists of Calcium Phosphates in a Collagenous Matrix	243	(1)
Basement Membranes Contain Type IV Collagen, Laminin, and Heparan Sulfate Proteoglycans	244	(3)
Fibronectin Glues Cells and Collagen Fibers Together	247	(1)
Proteoglycans Are Synthesized in the Endoplasmic Reticulum and Degraded in Lysosomes	248	(1)
Mucopolysaccharidoses Are Caused by the Deficiency of Glycosaminoglycan-Degrading Enzymes	249	(4)
Summary	249	(4)
PART FOUR INTEGRATION	253	(108)
Plasma Proteins	255	(32)
The Blood pH Is Tightly Regulated	255	(1)
Acidosis and Alkalosis Are Common in Clinical Practice	256	(1)
Most Plasma Proteins Are Derived from the Liver	257	(1)
Albumin Prevents Edema	258	(1)
Albumin Binds Many Small Molecules	258	(1)
Some Plasma Proteins Are Specialized Carriers of Small Molecules	259	(1)
The Deficiency of α1-Antiprotease Causes Lung Emphysema	260	(1)
The Levels of Plasma Proteins Are Affected by Many Diseases	261	(2)
Blood Components Are Used for Transfusions	263	(1)
Immunoglobulins Bind Antigens Very Selectively	263	(1)
Antibodies Consist of Two Light Chains and Two Heavy Chains	264	(1)
Different Immunoglobulin Classes Have Different Properties	265	(3)
Immunoglobulins Are Present on the Surface of B Lymphocytes	268	(1)
The Immunoglobulin Genes Are Rearranged during B Cell Development	269	(4)
Monoclonal Gammopathies Are Neoplastic Diseases of Plasma Cells	273	(1)
Blood Clotting Must Be Tightly Controlled	273	(1)
Platelets Adhere to Exposed Subendothelial Tissue	273	(2)
Insoluble Fibrin Is Formed from Soluble Fibrinogen	275	(1)
Thrombin Is Derived from Prothrombin	275	(1)
Factor X Can Be Activated by the Extrinsic and Intrinsic Pathways	276	(1)
Negative Controls Are Necessary to Prevent Thrombosis	277	(1)
Plasmin Degrades the Fibrin Clot	278	(2)
Heparin and the Vitamin K Antagonists Are the Most Important Anticoagulants	280	(1)
Clotting Factor Deficiencies Cause Abnormal Bleeding	281	(1)
Tissue Damage Causes the Release of Cellular Enzymes into the Blood	281	(1)
Serum Enzymes Are Used for the Diagnosis of Many Diseases	281	(6)
Summary	285	(2)
Extracellular Messengers	287	(26)
Steroid Hormones Are Made from Cholesterol	287	(1)
Progestins Are the Biosynthetic Precursors of All Other Steroid Hormones	287	(5)
Defects of Steroid Hormone Synthesis Cause Abnormalities of Sexual Development	292	(1)
Thyroid Hormones Are Synthesized from Protein-Bound Tyrosine	293	(1)
Both Hypothyroidism and Hyperthyroidism Are Common Disorders	293	(3)
The Catecholamines Are Synthesized from Tyrosine	296	(1)
Indolamines Are Synthesized from Tryptophan	296	(1)
Histamine Is Produced by Mast Cells and Basophils	297	(1)
Insulin Is Released Together with the C-Peptide	297	(1)
Some Prohormones Form More than One Active Product	298	(1)
Angiotensin Is Formed from Circulating Angiotensinogen	299	(2)
Radioimmunoassay Is the Most Versatile Method for the Determination of Hormone Levels	301	(1)
Arachidonic Acid Is Converted to Biologically Active Products	302	(1)
Prostaglandins Are Synthesized in Almost All Tissues	302	(1)
The Prostanoids Participate in Many Physiological Processes	303	(1)
The Leukotrienes Are Produced by the Lipoxygenase Pathway	304	(2)
Anti-Inflammatory Drugs Inhibit the Synthesis of Eicosanoids	306	(1)
Neurotransmitters Are Released at Synapses	306	(1)
Acetylcholine Is the Neurotransmitter of the Neuromuscular Junction	306	(2)
There Are Many Neurotransmitters	308	(5)
Summary	310	(3)
Intracellular Messengers	313	(22)
Receptor-Hormone Interactions Are Noncovalent, Reversible, and Saturable	313	(1)
Many Neurotransmitter Receptors Are Ion Channels	313	(2)
The Receptors for Steroid and Thyroid Hormones Are Transcription Factors	315	(1)
The Seven-Transmembrane Receptors Are Coupled to G Proteins	315	(1)
Adenylate Cyclase Is Regulated by G Proteins	316	(2)
Some Bacterial Toxins Modify G Proteins	318	(2)
Responses to Hormones Can Be Blocked at Several Levels	320	(1)
Cytoplasmic Calcium Is an Important Intracellular Signal	320	(1)
Phospholipase C Generates Two Second Messengers	320	(1)
Both cAMP and Calcium Regulate Gene Transcription	321	(2)
Muscle Contraction and Exocytosis Are Triggered by Calcium	323	(1)
The Receptor for Atrial Natriuretic Factor Is a Membrane-Bound Guanylate Cyclase	324	(1)
Nitric Oxide Stimulates a Soluble Guanylate Cyclase	324	(2)
cGMP Is a Second Messenger in Retinal Rod Cells	326	(1)
Receptors for Insulin and Growth Factors Contain a Protein Tyrosine Kinase Domain	327	(1)
Growth Factors and Insulin Trigger Multiple Signaling Cascades	328	(1)
Some Receptors Recruit Tyrosine-Specific Protein Kinases to the Membrane	329	(1)
The T Cell Receptor Recruits Cytosolic Tyrosine Protein Kinases	330	(1)
Many Receptors Become Desensitized after Overstimulation	331	(4)
Summary	333	(2)
Cellular Growth Control and Cancer	335	(26)
The Cell Cycle Is Controlled at Two Checkpoints	335	(1)
Cells Can Be Grown in Culture	335	(1)
The Cyclins Play Key Roles in Cell Cycle Control	336	(1)
The Retinoblastoma Protein Guards the G1 Checkpoint	337	(1)
Cell Proliferation Is Regulated by External Stimuli	337	(1)
Mitogens Regulate Gene Expression	338	(1)
Cells Can Commit Suicide	339	(1)
DNA Damage Causes Either Growth Arrest or Apoptosis	340	(1)
Cancers Are Monoclonal in Origin	341	(2)
Cancer Is Caused by the Activation of Growth-Promoting Genes and the Inactivation of Growth-Inhibiting Genes	343	(1)
Some Retroviruses Contain an Oncogene	344	(1)
Retroviruses Can Also Cause Cancer by Inserting Themselves Next to a Cellular Proto-oncogene	345	(2)
Many Oncogene Products Are Links in Mitogenic Signaling Chains	347	(2)
Retinoblastoma Is Caused by the Inactivation of a Tumor Suppressor Gene	349	(2)
Many Tumor Suppressor Genes Are Known	351	(1)
Components of the Cell Cycle Machinery Are Abnormal in Most Cancers	351	(2)
Mutations in the p53 Tumor Suppressor Gene Are the Most Common Genetic Changes in Spontaneous Cancers	353	(1)
Defects in p53-Regulating Proteins Can Also Contribute to Cancer	354	(1)
The P13K/Protein Kinase B Pathway Is Activated in Many Cancers	355	(1)
The Products of Some Viral Oncogenes Neutralize the Products of Cellular Tumor Suppressor Genes	356	(1)
Carcinogenesis Is a Multistep Process	357	(4)
Summary	359	(2)
PART FIVE METABOLISM	361	(220)
Digestive Enzymes	363	(8)
Saliva Contains α-Amylase and Lysozyme	363	(1)
Protein Digestion Starts in the Stomach	363	(2)
The Pancreas Is a Factory for Digestive Enzymes	365	(1)
Fat Digestion Requires Bile Salts	365	(1)
Some Digestive Enzymes Are Anchored to the Surface of the Microvilli	366	(1)
Not Everything Can Be Digested	366	(2)
Many Adults Have Poor Lactose Digestion	368	(1)
Many Digestive Enzymes Are Released as Inactive Precursors	369	(2)
Summary	370	(1)
Introduction to Metabolic Pathways	371	(6)
Metabolic Processes Are Compartmentalized	371	(1)
The Free Energy Changes in Metabolic Pathways Are Additive	371	(1)
Most Metabolic Pathways Are Regulated	372	(1)
Feedback Inhibition and Feedforward Stimulation Are the Most Important Regulatory Principles	373	(1)
Inherited Enzyme Deficiencies Cause Metabolic Diseases	374	(1)
Vitamin Deficiencies, Toxins, and Endocrine Disorders Can Also Disrupt Metabolic Pathways	375	(2)
Summary	375	(2)
Glycolysis, Tricarboxylic Acid Cycle, and Oxidative Phosphorylation	377	(30)
Glucose Is the Principal Transported Carbohydrate in Humans	377	(1)
Glucose Uptake into the Cells Is Regulated	377	(1)
Glucose Degradation Begins in the Cytoplasm and Ends in the Mitochondria	378	(1)
Glycolysis Begins with ATP-Dependent Phosphorylations	379	(1)
Most Glycolytic Intermediates Have Three Carbons	379	(3)
Phosphofructokinase Is the Most Important Regulated Enzyme of Glycolysis	382	(1)
Lactate Is Produced by Glycolysis under Anaerobic Conditions	382	(1)
Lactic Acid Accumulates in Many Metabolic Disorders	383	(1)
Genetic Defects and Toxins Can Inhibit Glycolysis	384	(1)
Pyruvate Is Decarboxylated to Acetyl-CoA in the Mitochondria	384	(1)
Acetyl-CoA Is Formed from Carbohydrates, Fatty Acids, and Amino Acids	384	(1)
The Pyruvate Dehydrogenase Reaction Is Impaired in Several Diseases	385	(1)
The TCA Cycle Produces Two Molecules of Carbon Dioxide for Each Acetyl Residue	386	(2)
Reduced Coenzymes Are the Most Important Products of the TCA Cycle	388	(1)
The Oxidative Pathways Are Regulated by Energy Charge and [NADH]/[NAD+] Ratio	389	(1)
The TCA Cycle Provides an Important Pool of Metabolic Intermediates	389	(2)
Most Intermediates of Mitochondrial Metabolism Can Be Transported across the Inner Mitochondrial Membrane	391	(1)
The Respiratory Chain Uses Molecular Oxygen to Oxidize NADH and FADH2	391	(2)
The Standard Reduction Potential Describes the Tendency to Donate Electrons	393	(1)
The Respiratory Chain Contains Flavoproteins, Iron-Sulfur Proteins, Cytochromes, Ubiquinone, and Protein-Bound Copper	394	(1)
The Respiratory Chain Contains Large Multiprotein Complexes	395	(1)
The Respiratory Chain Creates a Proton Gradient	396	(1)
The Proton Gradient Drives ATP Synthesis	397	(2)
The Efficiency of Glucose Oxidation Is Close to 40%	399	(1)
Oxidative Phosphorylation Is Limited by the Supply of ADP	400	(1)
Oxidative Phosphorylation Is Inhibited by Many Poisons	400	(1)
Oxygen Deficiency Is Rapidly Fatal	401	(1)
Inhibitors of Oxidative Phosphorylation Also Can Be Rapidly Fatal	402	(1)
Mutations in Mitochondrial DNA Can Cause Disease	403	(1)
Reactive Oxygen Derivatives Are Formed during Oxidative Metabolism	403	(4)
Summary	405	(2)
Carbohydrate Metabolism	407	(22)
An Adequate Blood Glucose Level Must Be Maintained at All Times	407	(1)
Three Irreversible Reactions of Glycolysis Must Be Bypassed in Gluconeogenesis	407	(1)
Fatty Acids Cannot Be Converted into Glucose	408	(1)
Hormones Are Important for the Regulation of Glycolysis and Gluconeogenesis	409	(1)
Glycolysis and Gluconeogenesis Are Fine-Tuned by Allosteric Effectors and Hormone-Induced Enzyme Phosphorylations	410	(2)
Carbohydrate Is Stored as Glycogen	412	(1)
Glycogen Is Readily Synthesized from Glucose	413	(1)
Glycogen Is Degraded by Phosphorolytic Cleavage	414	(2)
Glycogen Metabolism Is Regulated by Hormones and Metabolites	416	(2)
Glycogen Accumulates in Several Enzyme Deficiencies	418	(1)
Fructose Is Channeled into Glycolysis/Gluconeogenesis	419	(1)
Excess Fructose Is Toxic	419	(2)
Inborn Errors of Fructose Metabolism Cause Hypoglycemia and Liver Damage	421	(1)
Galactose Is Channeled into the Pathways of Glucose Metabolism	421	(1)
The Pentose Phosphate Pathway Supplies NADPH and Ribose-5-Phosphate	422	(2)
Glucose-6-Phosphage Dehydrogenase Deficiency Causes Drug-Induced Hemolytic Anemia	424	(1)
Fructose Is the Principal Sugar in Seminal Fluid	425	(1)
Amino Sugars and Sugar Acids Are Made from Glucose	425	(4)
Summary	427	(2)
The Metabolism of Fatty Acids and Triglycerides	429	(18)
Fatty Acids Differ in Their Chain Length and the Number of Carbon-Carbon Double Bonds	429	(1)
Chylomicrons Transport Triglycerides from the Intestine to Other Tissues	430	(2)
Adipose Tissue Is Specialized for the Storage of Triglycerides	432	(1)
Fat Metabolism in Adipose Tissue Is under Hormonal Control	433	(1)
Fatty Acids Are Transported into the Mitochondrion	434	(1)
β-Oxidation Produces Acetyl-CoA, NADH, and FADH2	434	(1)
Special Fatty Acids Require Special Reactions	435	(1)
The Liver Converts Excess Fatty Acids to Ketone Bodies	436	(2)
Defects of β-Oxidation Cause Muscle Weakness and Fasting Hypoglycemia	438	(1)
Fatty Acids are Synthesized from Acetyl-CoA	439	(2)
Acetyl-CoA Is Shuttled into the Cytoplasm as Citrate	441	(1)
Fatty Acid Synthesis Is Regulated by Hormones and Metabolites	442	(1)
Most Fatty Acids Can Be Synthesized from Palmitate	442	(1)
Fatty Acids Can Regulate Gene Expression	443	(1)
Polyunsaturated Fatty Acids Can Be Oxidized Nonenzymatically	444	(3)
Summary	445	(2)
The Metabolism of Membrane Lipids	447	(14)
Phosphatidic Acid Is an Intermediate in Phosphoglyceride Synthesis	447	(1)
Phosphoglycerides Are Remodeled Continuously	447	(2)
Sphingolipids Are Synthesized from Ceramide	449	(2)
The ABO Blood Group Substances Are Oligosaccharides in Glycosphingolipids	451	(1)
Deficiencies of Sphingolipid-Degrading Enzymes Cause Lipid Storage Diseases	451	(1)
Cholesterol Is the Least Soluble Membrane Lipid	452	(1)
Cholesterol Is Derived from Both Endogenous Synthesis and the Diet	453	(1)
Cholesterol Biosynthesis Is Regulated at the Level of HMG-CoA Reductase	454	(1)
The Isoprenoids Are Derived from the Pathway of Cholesterol Biosynthesis	455	(1)
Bile Acids Are Synthesized from Cholesterol	455	(1)
Bile Acid Synthesis Is Feedback-Inhibited	455	(1)
Bile Acids Are Subject to Extensive Enterohepatic Circulation	455	(2)
Most Gallstones Consist of Cholesterol	457	(4)
Summary	458	(3)
Lipid Transport	461	(18)
Most Plasma Lipids Are Components of Lipoproteins	461	(1)
Lipoproteins Have Characteristic Lipid and Protein Compositions	462	(1)
Lipids of Dietary Origin Are Transported by Chylomicrons	462	(1)
VLDL Is a Precursor of LDL	463	(3)
LDL Is Removed by Receptor-Mediated Endocytosis	466	(1)
Cholesterol Regulates Its Own Metabolism	466	(1)
HDL Is Needed for Reverse Cholesterol Transport	467	(1)
Lipoproteins Are Risk Factors for Atherosclerosis	468	(2)
Genes and Diet Are Risk Factors for Atherosclerosis	470	(1)
Deficiencies of Individual Lipoprotein Classes Are Causes of Severe Diseases	471	(1)
Defects of LDL Receptors Cause Familial Hypercholesterolemia	471	(1)
Deficiencies of LCAT and CETP Prevent Reverse Cholesterol Transport	471	(2)
Hyperlipoproteinemias Are Grouped into Five Phenotypes	473	(2)
Both Diet and Drugs Affect Plasma Lipoproteins	475	(4)
Summary	475	(4)
Amino Acid Metabolism	479	(24)
Most Amino Acids in the Human Body Are Present as Constituents of Proteins	479	(1)
The Nitrogen Balance Indicates the Net Rate of Protein Synthesis	480	(1)
The Amino Group of the Amino Acids Is Released as Ammonia	480	(1)
Ammonia Is Detoxified into Urea	481	(2)
Urea Is Synthesized in the Urea Cycle	483	(1)
Failure of the Urea Cycle Causes Hyperammonemia and Central Nervous System Dysfunction	484	(1)
Some Amino Acids Are Closely Related to Common Metabolic Intermediates	485	(1)
Glycine, Serine, and Threonine Are Glucogenic	486	(1)
Proline, Arginine, Ornithine, and Histidine Are Degraded to Glutamate	487	(2)
Methionine and Cysteine Are Metabolically Related	489	(2)
Homocysteine Is a Risk Factor for Vascular Disease	491	(1)
The Degradation of Valine, Leucine, and Isoleucine Begins with Transamination and Oxidative Decarboxylation	491	(2)
Phenylalanine and Tyrosine Are Both Glucogenic and Ketogenic	493	(1)
Phenylketonuria Causes Mental Deficiency	494	(2)
Lysine and Tryptophan Have Lengthy Catabolic Pathways	496	(1)
The Liver Is the Most Important Organ of Amino Acid Metabolism	497	(1)
Glutamine Participates in Renal Acid-Base Regulation	498	(2)
Amino Acid Transport Defects Can Cause Disease	500	(1)
Creatine Phosphate Forms a Store of Energy-Rich Phosphate Bonds in Muscle Tissue	500	(1)
Melanin Is Synthesized from Tyrosine	501	(2)
Summary	501	(2)
Heme Metabolism	503	(8)
Bone Marrow and the Liver Are the Most Important Sites of Heme Synthesis	503	(1)
Heme Is Synthesized from Succinyl-CoA and Glycine	504	(1)
Porphyrias Are Caused by Deficiencies of Heme-Synthesizing Enzymes	505	(1)
Heme Is Degraded to Bilirubin	506	(1)
Bilirubin Is Conjugated and Excreted by the Liver	506	(1)
Elevations of Serum Bilirubin Cause Jaundice	507	(1)
Unconjugated Hyperbilirubinemia Is Most Common in Newborns	508	(1)
Biliary Obstruction Causes Conjugated Hyperbilirubinemia	509	(2)
Summary	510	(1)
The Metabolism of Purines and Pyrimidines	511	(12)
Purine Synthesis Starts with Ribose-5-Phosphate	511	(1)
Purines Are Degraded to Uric Acid	512	(1)
Free Purine Bases Can Be Salvaged	512	(1)
Pyrimidines Are Synthesized from Carbamoyl Phosphate and Aspartate	512	(1)
DNA Synthesis Requires Deoxyribonucleotides	513	(1)
Many Antineoplastic Drugs Inhibit Nucleotide Metabolism	514	(5)
Some Immunodeficiency Diseases Are Caused by Defects in Nucleotide Metabolism	519	(1)
Uric Acid Has Limited Water Solubility	519	(1)
Hyperuricemia Causes Gout	520	(1)
Some Patients with Gout Have Abnormalities of Purine-Metabolizing Enzymes	521	(1)
Gout Can Be Treated with Drugs	521	(2)
Summary	522	(1)
Vitamins and Minerals	523	(26)
Riboflavin Is a Precursor of FMN and FAD	523	(1)
Niacin Is a Precursor of NAD and NADP	524	(2)
Thiamine Deficiency Causes Weakness and Amnesia	526	(1)
Vitamin B6 Plays a Key Role in Amino Acid Metabolism	527	(1)
Pantothenic Acid Is a Building Block of Coenzyme A	528	(1)
Biotin Is a Coenzyme in Carboxylation Reactions	529	(1)
Folic Acid Deficiency Causes Megaloblastic Anemia	530	(2)
Pernicious Anemia Is Caused by the Malabsorption of Vitamin B12	532	(1)
Vitamin C Is a Water-Soluble Antioxidant	533	(1)
Retinol, Retinal, and Retinoic Acid Are the Active Forms of Vitamin A	534	(2)
Vitamin D Is a Prohormone	536	(2)
Vitamin E Is an Important Antioxidant	538	(1)
Vitamin K Is Required for Blood Clotting	539	(1)
Iron Is Conserved Very Efficiently in the Body	540	(2)
Iron Deficiency Is the Most Common Micronutrient Deficiency Worldwide	542	(2)
Iron Overload Can Cause Disease	544	(1)
Zinc Is a Constituent of Many Enzymes	544	(1)
Copper Participates in Reactions of Molecular Oxygen	545	(1)
Some Trace Elements Serve Very Specific Functions	545	(4)
Summary	546	(3)
Integration of Metabolism	549	(32)
Insulin Is a Satiety Hormone	549	(1)
Glucagon Maintains the Blood Glucose Level	549	(1)
Catecholamines Mediate the Flight-or-Fight Response	550	(1)
Glucocorticoids Are Released in Chronic Stress	551	(1)
Energy Must Be Provided Continuously	552	(1)
Adipose Tissue Is the Most Important Energy Depot	553	(1)
The Liver Converts Dietary Carbohydrates to Glycogen and Fat	554	(1)
The Liver Supplies Glucose and Ketone Bodies during Fasting	555	(1)
Most Tissues Switch from Carbohydrate Oxidation to Fat Oxidation during Fasting	556	(1)
Obesity Is the Most Common Nutrition-Related Disorder in Affluent Countries	557	(4)
Diabetes Is Caused by Insulin Deficiency or Insulin Resistance	561	(1)
In Diabetes, Metabolism Is Regulated as in Starvation	562	(1)
Diabetes Is Diagnosed with Laboratory Tests	563	(1)
Diabetes Leads to Late Complications	564	(1)
Contracting Muscle Has Three Energy Sources	564	(2)
The Catecholamines Coordinate Metabolism during Exercise	566	(2)
Physical Endurance Depends on Oxidative Capacity and Muscle Glycogen Stores	568	(1)
Lipophilic Xenobiotics Are Metabolized to Water-Soluble Products	569	(1)
Xenobiotic Metabolism Requires Cytochrome P-450	569	(1)
Ethanol Is Metabolized to Acetyl-CoA in the Liver	570	(3)
Liver Metabolism Is Deranged by Alcohol	573	(1)
Alcoholism Leads to Fatty Liver and Liver Cirrhosis	573	(2)
Most ``Diseases of Civilization'' Are Caused by Aberrant Nutrition	575	(2)
Aging Is the Greatest Challenge for Medical Research	577	(4)
Summary	578	(3)
Case Studies	581	(24)
Answers to Case Studies	605	(18)
Answers to Questions	623	(2)
Glossary	625	(24)
Credits	649	(2)
Index	651