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Book Details
Abstract
For nearly 30 years, Principles of Medical Biochemistry has integrated medical biochemistry with molecular genetics, cell biology, and genetics to provide complete yet concise coverage that links biochemistry with clinical medicine. The 4th Edition of this award-winning text by Drs. Gerhard Meisenberg and William H. Simmons has been fully updated with new clinical examples, expanded coverage of recent changes in the field, and many new case studies online. A highly visual format helps readers retain complex information, and USMLE-style questions (in print and online) assist with exam preparation.
- Just the right amount of detail on biochemistry, cell biology, and genetics – in one easy-to-digest textbook.
- Full-color illustrations and tables throughout help students master challenging concepts more easily.
- Online case studies serve as a self-assessment and review tool before exams.
- Online access includes nearly 150 USMLE-style questions in addition to the questions that are in the book.
- Glossary of technical terms.
- Clinical Boxes and Clinical Content demonstrate the integration of basic sciences and clinical applications, helping readers make connections between the two. New clinical examples have been added throughout the text.
Table of Contents
| Section Title | Page | Action | Price |
|---|---|---|---|
| Front Cover | Cover | ||
| Inside Front Cover | ES2 | ||
| Principles of Medical Biochemistry | iii | ||
| Copyright | iv | ||
| Preface | v | ||
| Faculty resources | v | ||
| Contents | vii | ||
| Part One Principles of Molecular Structure and Function | 1 | ||
| Chapter 1 Introduction to Biomolecules | 2 | ||
| Water is the solvent of life | 2 | ||
| Water contains hydronium ions and hydroxyl ions | 3 | ||
| Ionizable groups are characterized by their pk values | 4 | ||
| The blood pH is tightly regulated | 4 | ||
| Acidosis and alkalosis are common in clinical practice | 5 | ||
| Bonds are formed by reactions between functional groups | 6 | ||
| Isomeric forms are common in biomolecules | 7 | ||
| Properties of biomolecules are determined by their noncovalent interactions | 8 | ||
| Triglycerides consist of fatty acids and glycerol | 10 | ||
| Monosaccharides are polyalcohols with a keto group or an aldehyde group | 10 | ||
| Monosaccharides form ring structures | 11 | ||
| Complex carbohydrates are formed by glycosidic bonds | 11 | ||
| Polypeptides are formed from amino acids | 14 | ||
| Nucleic acids are formed from nucleotides | 14 | ||
| Most biomolecules are polymers | 15 | ||
| Summary | 16 | ||
| Questions | 16 | ||
| Chapter 2 Introduction to Protein Structure | 18 | ||
| Amino acids are zwitterions | 18 | ||
| Amino acid side chains form many noncovalent interactions | 19 | ||
| Peptide bonds and disulfide bonds form the primary structure of proteins | 20 | ||
| Proteins can fold themselves into many shapes | 22 | ||
| α-helix and β-pleated sheet are the most common secondary structures in proteins | 22 | ||
| Globular proteins have a hydrophobic core | 23 | ||
| Proteins lose their biological activities when their higher-order structure is destroyed | 24 | ||
| The solubility of proteins depends on pH and salt concentration | 25 | ||
| Proteins absorb ultraviolet radiation | 26 | ||
| Proteins can be separated by their charge or their molecular weight | 26 | ||
| Abnormal protein aggregates can cause disease | 27 | ||
| Neurodegenerative diseases are caused by protein aggregates | 29 | ||
| Protein misfolding can be contagious | 30 | ||
| Summary | 31 | ||
| Further Reading | 31 | ||
| Questions | 31 | ||
| Chapter 3 Oxygen-Binding Proteins: Hemoglobin and Myoglobin | 33 | ||
| The heme group is the oxygen-binding site of hemoglobin and myoglobin | 33 | ||
| Myoglobin is a tightly packed globular protein | 34 | ||
| Red blood cells are specialized for oxygen transport | 34 | ||
| The hemoglobins are tetrameric proteins | 34 | ||
| Oxygenated and deoxygenated hemoglobin have different quaternary structures | 36 | ||
| Oxygen binding to hemoglobin is cooperative | 36 | ||
| 2,3-Bisphosphoglycerate is a negative allosteric effector of oxygen binding to hemoglobin | 37 | ||
| Fetal hemoglobin has a higher oxygen-binding affinity than does adult hemoglobin | 38 | ||
| The bohr effect facilitates oxygen delivery | 39 | ||
| Most carbon dioxide is transported as bicarbonate | 39 | ||
| Summary | 40 | ||
| Further Reading | 40 | ||
| Questions | 40 | ||
| Chapter 4 Enzymatic Reactions | 41 | ||
| The equilibrium constant describes the equilibrium of the reaction | 41 | ||
| The free energy change is the driving force for chemical reactions | 42 | ||
| The standard free energy change determines the equilibrium | 43 | ||
| Enzymes are both powerful and selective | 43 | ||
| The substrate must bind to its enzyme before the reaction can proceed | 44 | ||
| Rate constants are useful for describing reaction rates | 44 | ||
| Enzymes decrease the free energy of activation | 45 | ||
| Many enzymatic reactions can be described by michaelis-menten kinetics | 46 | ||
| Km and vmax can be determined graphically | 47 | ||
| Substrate half-life can be determined for first-order but not zero-order reactions | 48 | ||
| Kcat/km predicts the enzyme activity at low substrate concentration | 48 | ||
| Allosteric enzymes do not conform to michaelis-menten kinetics | 48 | ||
| Enzyme activity depends on temperature and pH | 49 | ||
| Different types of reversible enzyme inhibition can be distinguished kinetically | 49 | ||
| Covalent modification can inhibit enzymes irreversibly | 51 | ||
| Enzymes stabilize the transition state | 51 | ||
| Chymotrypsin forms a transient covalent bond during catalysis | 52 | ||
| Summary | 53 | ||
| Further Reading | 53 | ||
| Questions | 54 | ||
| Chapter 5 Coenzymes | 55 | ||
| Enzymes are classified according to their reaction type | 55 | ||
| Oxidoreductases | 55 | ||
| Transferases | 56 | ||
| Hydrolases | 56 | ||
| Lyases | 56 | ||
| Isomerases | 56 | ||
| Ligases | 56 | ||
| Adenosine triphosphate has two energy-rich bonds | 56 | ||
| ATP DONATES phosphate in phosphorylation reactions | 58 | ||
| ATP hydrolysis drives endergonic reactions | 59 | ||
| Cells always try to maintain a high energy charge | 59 | ||
| Dehydrogenase reactions require specialized coenzymes | 59 | ||
| Coenzyme a activates organic acids | 60 | ||
| S -adenosyl methionine donates methyl groups | 62 | ||
| Many enzymes require a metal ion | 62 | ||
| Summary | 63 | ||
| Questions | 63 | ||
| Part Two Genetic Information: DNA, RNA, and Protein SYnthesis | 65 | ||
| Chapter 6 DNA, RNA, and Protein Synthesis | 66 | ||
| All living organisms use dna as their genetic databank | 66 | ||
| DNA contains four bases | 68 | ||
| DNA forms a double helix | 68 | ||
| DNA can be denatured | 69 | ||
| DNA is supercoiled | 69 | ||
| DNA replication is semiconservative | 70 | ||
| DNA is synthesized by DNA polymerases | 70 | ||
| DNA polymerases have exonuclease activities | 71 | ||
| Unwinding proteins present a single-stranded template to the DNA polymerases | 72 | ||
| One of the new DNA strands is synthesized discontinuously | 74 | ||
| RNA plays key roles in gene expression | 76 | ||
| The σ subunit recognizes promoters | 76 | ||
| DNA is faithfully copied into RNA | 77 | ||
| Some RNAs are chemically modified after transcription | 79 | ||
| The genetic code defines the structural relationship between mRNA and polypeptide | 80 | ||
| Transfer RNA is the adapter molecule in protein synthesis | 81 | ||
| Amino acids are activated by an ester bond with the 3′ terminus of the tRNA | 82 | ||
| Many transfer RNAs recognize more than one codon | 83 | ||
| Ribosomes are the workbenches for protein synthesis | 83 | ||
| The initiation complex brings together ribosome, messenger RNA, and initiator tRNA | 85 | ||
| Polypeptides grow stepwise from the amino terminus to the carboxyl terminus | 85 | ||
| Protein synthesis is energetically expensive | 88 | ||
| Gene expression is tightly regulated | 88 | ||
| A repressor protein regulates transcription of the lac operon in E. coli | 88 | ||
| Anabolic operons are repressed by the end product of the pathway | 89 | ||
| Glucose regulates the transcription of many catabolic operons | 90 | ||
| Transcriptional regulation depends on DNA-binding proteins | 91 | ||
| Summary | 92 | ||
| Further Reading | 92 | ||
| Questions | 93 | ||
| Chapter 7 The Human Genome | 94 | ||
| Chromatin consists of DNA and histones | 94 | ||
| The nucleosome is the structural unit of chromatin | 95 | ||
| Covalent histone modifications regulate DNA replication and transcription | 95 | ||
| DNA methylation silences genes | 95 | ||
| All eukaryotic chromosomes have a centromere, telomeres, and replication origins | 97 | ||
| Telomerase is required (but not sufficient) for immortality | 97 | ||
| Eukaryotic DNA replication requires three DNA polymerases | 99 | ||
| Most human DNA does not code for proteins | 100 | ||
| Gene families originate by gene duplication | 100 | ||
| The genome contains many tandem repeats | 101 | ||
| Some DNA sequences are copies of functional RNAs | 101 | ||
| Many repetitive DNA sequences are (or were) mobile | 102 | ||
| L1 elements encode a reverse transcriptase | 103 | ||
| ALU sequences spread with the help of L1 reverse transcriptase | 105 | ||
| Mobile elements are dangerous | 105 | ||
| Humans have approximately 20,000 genes | 105 | ||
| Transcriptional initiation requires general transcription factors | 106 | ||
| Genes are surrounded by regulatory sites | 107 | ||
| Gene expression is regulated by DNA-binding proteins | 107 | ||
| Long noncoding RNAs play roles in gene expression | 108 | ||
| mRNA processing starts during transcription | 109 | ||
| Translational initiation requires many initiation factors | 111 | ||
| mRNA processing and translation are often regulated | 113 | ||
| Regulation of Messenger RNA Stability | 113 | ||
| Tissue-Specific Initiation and Termination of Transcription | 113 | ||
| Alternative Splicing | 113 | ||
| Translational Repressors | 113 | ||
| mRNA Editing | 113 | ||
| Small RNA molecules inhibit gene expression | 115 | ||
| Mitochondria have their own DNA | 116 | ||
| Human genomes are very diverse | 117 | ||
| Human genomes have many low-frequency copy number variations | 117 | ||
| Summary | 118 | ||
| Further Reading | 118 | ||
| Questions | 119 | ||
| Chapter 8 Protein Targeting and Proteostasis | 120 | ||
| A signal sequence directs polypeptides to the endoplasmic reticulum | 120 | ||
| Glycoproteins are processed in the secretory pathway | 121 | ||
| The endocytic pathway brings proteins into the cell | 124 | ||
| Lysosomes are organelles of intracellular digestion | 126 | ||
| Autophagy recycles cellular proteins and organelles | 127 | ||
| Poorly folded proteins are either repaired or destroyed | 127 | ||
| Ubiquitin marks proteins for destruction | 127 | ||
| The proteostatic system protects cells from abnormal proteins | 129 | ||
| Summary | 131 | ||
| Further Reading | 131 | ||
| Questions | 131 | ||
| Chapter 9 Introduction to Genetic Diseases | 132 | ||
| Four types of genetic disease | 132 | ||
| Mutations occur in the germline and in somatic cells | 133 | ||
| Mutations are an important cause of poor health | 134 | ||
| Small mutations lead to abnormal proteins | 134 | ||
| Most mutations are caused by replication errors | 135 | ||
| Mutations can be induced by radiation and chemicals | 135 | ||
| Mismatch repair corrects replication errors | 136 | ||
| Missing bases and abnormal bases need to be replaced | 138 | ||
| Nucleotide excision repair removes bulky lesions | 139 | ||
| Repair of dna double-strand breaks is difficult | 139 | ||
| Hemoglobin genes form two gene clusters | 141 | ||
| Many point mutations in hemoglobin genes are known | 142 | ||
| Sickle cell disease is caused by a point mutation in the β-chain gene | 143 | ||
| SA heterozygotes are protected from tropical malaria | 144 | ||
| α-thalassemia is most often caused by large deletions | 145 | ||
| Many different mutations can cause β-thalassemia | 146 | ||
| Fetal hemoglobin protects from the effects of β-thalassemia and sickle cell disease | 147 | ||
| Polygenic diseases have multiple genetic risk factors | 147 | ||
| Genetic risk factors are discovered in genome-wide association studies | 148 | ||
| Summary | 149 | ||
| Further Reading | 149 | ||
| Questions | 150 | ||
| Chapter 10 Viruses | 152 | ||
| Viruses can replicate only in a host cell | 152 | ||
| Bacteriophage T4 destroys its host cell | 153 | ||
| DNA viruses substitute their own DNA for the host cell DNA | 153 | ||
| λ phage can integrate its DNA into the host cell chromosome | 154 | ||
| RNA viruses require an RNA-dependent RNA polymerase | 157 | ||
| Retroviruses replicate through a DNA intermediate | 157 | ||
| Plasmids are small “accessory chromosomes” or “symbiotic viruses” of bacteria | 160 | ||
| Bacteria can exchange genes by transformation and transduction | 160 | ||
| Jumping genes can change their position in the genome | 162 | ||
| Summary | 164 | ||
| Further Reading | 164 | ||
| Questions | 164 | ||
| Chapter 11 DNA Technology | 165 | ||
| Restriction endonucleases cut large DNA molecules into smaller fragments | 165 | ||
| Large probes are used to detect copy number variations | 165 | ||
| Small probes are used to detect point mutations | 166 | ||
| Southern blotting determines the size of restriction fragments | 167 | ||
| DNA can be amplified with the polymerase chain reaction | 168 | ||
| PCR is used for preimplantation genetic diagnosis | 169 | ||
| Allelic heterogeneity is the greatest challenge for molecular genetic diagnosis | 170 | ||
| Normal polymorphisms are used as genetic markers | 170 | ||
| Tandem repeats are used for DNA fingerprinting | 171 | ||
| DNA microarrays can be used for genetic screening | 172 | ||
| DNA microarrays are used for the study of gene expression | 174 | ||
| DNA is sequenced by controlled chain termination | 174 | ||
| Massively parallel sequencing permits cost-efficient whole-genome genetic diagnosis | 175 | ||
| Gene therapy targets somatic cells | 177 | ||
| Viruses are used as vectors for gene therapy | 177 | ||
| Retroviruses can splice a transgene into the cell’s genome | 178 | ||
| Genome editing is based on the making and healing of DNA double strand breaks | 179 | ||
| Designer nucleases are used for genome editing | 180 | ||
| Antisense oligonucleotides can block the expression of rogue genes | 181 | ||
| Genes can be altered in animals | 181 | ||
| Tissue-specific gene expression can be engineered into animals | 183 | ||
| Human germline genome editing is technically possible | 184 | ||
| Summary | 184 | ||
| Further Reading | 184 | ||
| Questions | 185 | ||
| Part Three Cell and Tissue Structure | 187 | ||
| Chapter 12 Biological Membranes | 188 | ||
| Membranes consist of lipid and protein | 188 | ||
| Phosphoglycerides are the most abundant membrane lipids | 188 | ||
| Most sphingolipids are glycolipids | 190 | ||
| Cholesterol is the most hydrophobic membrane lipid | 191 | ||
| Membrane lipids form a bilayer | 192 | ||
| The lipid bilayer is a two-dimensional fluid | 192 | ||
| The lipid bilayer is a diffusion barrier | 193 | ||
| Membranes contain integral and peripheral membrane proteins | 194 | ||
| Membranes are asymmetrical | 194 | ||
| Membranes are fragile | 196 | ||
| Membrane proteins carry solutes across the lipid bilayer | 196 | ||
| Transport against an electrochemical gradient requires metabolic energy | 198 | ||
| Active transport consumes ATP | 199 | ||
| Sodium cotransport brings molecules into the cell | 199 | ||
| Summary | 201 | ||
| Further Reading | 201 | ||
| Questions | 201 | ||
| Chapter 13 The Cytoskeleton | 203 | ||
| The erythrocyte membrane is reinforced by a spectrin network | 203 | ||
| Keratins give strength to epithelia | 204 | ||
| Actin filaments are formed from globular subunits | 206 | ||
| Striated muscle contains thick and thin filaments | 207 | ||
| Myosin is a two-headed molecule with atpase activity | 207 | ||
| Muscle contraction requires calcium and ATP | 210 | ||
| The cytoskeleton of skeletal muscle is linked to the extracellular matrix | 211 | ||
| Microtubules consist of tubulin | 213 | ||
| Eukaryotic cilia and flagella contain a 9+2 array of microtubules | 214 | ||
| Cells form specialized junctions with other cells and with the extracellular matrix | 214 | ||
| Summary | 216 | ||
| Further Reading | 216 | ||
| Questions | 217 | ||
| Chapter 14 The Extracellular Matrix | 218 | ||
| Collagen is the most abundant protein in the human body | 218 | ||
| The Tropocollagen molecule forms a long triple helix | 220 | ||
| Collagen fibrils are staggered arrays of tropocollagen molecules | 220 | ||
| Collagen is subject to extensive posttranslational processing | 220 | ||
| Collagen metabolism is altered in aging and disease | 222 | ||
| Many genetic defects of collagen structure and biosynthesis are known | 223 | ||
| Elastic fibers contain elastin and fibrillin | 224 | ||
| The amorphous ground substance contains hyaluronic acid | 225 | ||
| Sulfated glycosaminoglycans are covalently bound to core proteins | 226 | ||
| Cartilage contains large proteoglycan aggregates | 227 | ||
| Proteoglycans are synthesized in the er and degraded in lysosomes | 228 | ||
| Mucopolysaccharidoses are caused by deficiency of glycosaminoglycan-degrading enzymes | 229 | ||
| Bone consists of calcium phosphates in a collagenous matrix | 230 | ||
| Basement membranes contain type iv collagen, laminin, and heparan sulfate proteoglycans | 230 | ||
| Fibronectin glues cells and collagen fibers together | 231 | ||
| Summary | 232 | ||
| Further Reading | 233 | ||
| Questions | 234 | ||
| Part Four Molecular Physiology | 235 | ||
| Chapter 15 Extracellular Messengers | 236 | ||
| Steroid hormones are made from cholesterol | 236 | ||
| Progestins are the biosynthetic precursors of all other steroid hormones | 238 | ||
| Thyroid hormones are synthesized from protein-bound tyrosine | 242 | ||
| T4 becomes activated to T3 in the target tissues | 243 | ||
| Both hypothyroidism and hyperthyroidism are common disorders | 244 | ||
| Insulin is released together with the C-peptide | 245 | ||
| Proopiomelanocortin forms several active products | 245 | ||
| Angiotensin is formed from circulating angiotensinogen | 246 | ||
| Immunoassays are used for determination of hormone levels | 247 | ||
| Catecholamines are synthesized from tyrosine | 249 | ||
| Indoleamines are synthesized from tryptophan | 249 | ||
| Histamine is produced by mast cells and basophils | 251 | ||
| Neurotransmitters are released at synapses | 251 | ||
| Acetylcholine is the neurotransmitter of the neuromuscular junction | 252 | ||
| There are many neurotransmitters | 252 | ||
| Summary | 254 | ||
| Further Reading | 254 | ||
| Questions | 255 | ||
| Chapter 16 Intracellular Messengers | 256 | ||
| Receptor-hormone interactions are noncovalent, reversible, and saturable | 256 | ||
| Many neurotransmitter receptors are ion channels | 257 | ||
| Steroid and thyroid hormones bind to transcription factors | 258 | ||
| Seven-transmembrane receptors are coupled to G proteins | 258 | ||
| Adenylate cyclase is regulated by G proteins | 260 | ||
| Hormones can both activate and inhibit the camp cascade | 261 | ||
| Cytoplasmic calcium is an important intracellular signal | 263 | ||
| Phospholipase C generates two second messengers | 263 | ||
| Both camp and calcium regulate gene transcription | 264 | ||
| Muscle contraction and exocytosis are triggered by calcium | 265 | ||
| Atrial natriuretic factor acts through a membrane-bound guanylate cyclase | 265 | ||
| Nitric oxide stimulates a soluble guanylate cyclase | 267 | ||
| cGMP is a second messenger in retinal rod cells | 268 | ||
| Receptors for insulin and growth factors are tyrosine-specific protein kinases | 269 | ||
| Growth factors and insulin trigger multiple signaling cascades | 271 | ||
| Cytokine receptors use the JAK-STAT pathway | 271 | ||
| Many receptors become desensitized after overstimulation | 273 | ||
| Summary | 273 | ||
| Further Reading | 273 | ||
| Questions | 274 | ||
| Chapter 17 Plasma Proteins | 275 | ||
| Plasma proteins are both synthesized and destroyed in the liver | 275 | ||
| Albumin prevents edema | 275 | ||
| Albumin binds many small molecules | 277 | ||
| Some plasma proteins are specialized carriers of small molecules | 277 | ||
| Deficiency of α1 -antitrypsin causes lung emphysema | 278 | ||
| Levels of plasma proteins are affected by many diseases | 279 | ||
| Blood components are used for transfusions | 280 | ||
| Blood clotting must be tightly controlled | 281 | ||
| Platelets adhere to exposed subendothelial tissue | 281 | ||
| Insoluble fibrin is formed from soluble fibrinogen | 283 | ||
| Thrombin is derived from prothrombin | 284 | ||
| Factor X can be activated by the extrinsic and intrinsic pathways | 284 | ||
| Negative controls are necessary to prevent thrombosis | 286 | ||
| Plasmin degrades the fibrin clot | 287 | ||
| Heparin and vitamin K antagonists are used as anticoagulants | 288 | ||
| Clotting factor deficiencies cause abnormal bleeding | 289 | ||
| Tissue damage causes release of cellular enzymes into blood | 289 | ||
| Serum Enzymes are Used for the Diagnosis of Many Diseases | 290 | ||
| Plasma Cholinesterase | 290 | ||
| Transaminases | 290 | ||
| Alkaline Phosphatase | 291 | ||
| γ -Glutamyl Transferase | 291 | ||
| Acid Phosphatase and Prostate-Specific Antigen | 291 | ||
| Lactate Dehydrogenase (LDH) | 291 | ||
| Creatine Kinase | 292 | ||
| Pancreatic enzymes | 292 | ||
| Summary | 292 | ||
| Further Reading | 293 | ||
| Questions | 293 | ||
| Chapter 18 Defense Mechanisms | 294 | ||
| Lipophilic xenobiotics are metabolized to water-soluble products | 294 | ||
| Cytochrome P-450 is involved in phase I metabolism | 294 | ||
| Phase II metabolism makes xenobiotics water-soluble for excretion | 296 | ||
| Phase III metabolism excretes xenobiotic metabolites | 297 | ||
| Drug-metabolizing enzymes are inducible | 298 | ||
| The innate immune system uses pattern recognition receptors | 298 | ||
| Infection triggers inflammation | 299 | ||
| Lymphocytes possess antigen receptors | 300 | ||
| B Lymphocytes produce immunoglobulins | 301 | ||
| Antibodies consist of two light chains and two heavy chains | 301 | ||
| Different immunoglobulin classes have different properties | 303 | ||
| Adaptive immune responses are based on clonal selection | 305 | ||
| Immunoglobulin genes are rearranged during B-cell development | 306 | ||
| The T-cell receptor recruits cytosolic tyrosine protein kinases | 309 | ||
| Mediators of inflammation are produced from arachidonic acid | 310 | ||
| Prostaglandins are synthesized in all tissues | 311 | ||
| Prostanoids participate in many physiological processes | 312 | ||
| Leukotrienes are produced by the lipoxygenase pathway | 312 | ||
| Antiinflammatory drugs inhibit the synthesis of eicosanoids | 312 | ||
| Summary | 314 | ||
| Further Reading | 314 | ||
| Questions | 315 | ||
| Chapter 19 Cellular Growth Control and Cancer | 316 | ||
| The cell cycle is controlled at checkpoints | 316 | ||
| Cells can be grown in culture | 317 | ||
| Cyclins play key roles in cell cycle control | 317 | ||
| Retinoblastoma protein guards the G1 checkpoint | 317 | ||
| Cell proliferation is triggered by mitogens | 318 | ||
| Mitogens regulate gene expression | 319 | ||
| Cells can commit suicide | 320 | ||
| Cancers are monoclonal in origin | 322 | ||
| Cancer is caused by activation of growth-promoting genes and inactivation of growth-inhibiting genes | 323 | ||
| Some retroviruses contain an oncogene | 324 | ||
| Retroviruses can cause cancer by inserting themselves next to a cellular proto-oncogene | 325 | ||
| Many oncogenes code for components of mitogenic signaling cascades | 326 | ||
| Growth Factors | 326 | ||
| Receptor Tyrosine Kinases | 326 | ||
| Nonreceptor Tyrosine Protein Kinases | 327 | ||
| Cytoplasmic Serine/Threonine Kinases | 327 | ||
| G Proteins | 327 | ||
| Nuclear Transcription Factors | 328 | ||
| Cancer susceptibility syndromes are caused by inherited mutations in tumor suppressor genes | 329 | ||
| Many tumor suppressor genes are known | 330 | ||
| Components of the cell cycle machinery are abnormal in most cancers | 331 | ||
| DNA Damage causes either growth arrest or apoptosis | 332 | ||
| Most spontaneous cancers are defective in p53 action | 333 | ||
| The PI3K/protein kinase B pathway is activated in many cancers | 334 | ||
| The products of some viral oncogenes neutralize the products of cellular tumor suppressor genes | 334 | ||
| Tumors become more malignant through darwinian selection | 336 | ||
| Intestinal polyps are benign lesions | 336 | ||
| Intestinal polyps can evolve into colon cancer | 337 | ||
| Summary | 338 | ||
| Further Reading | 338 | ||
| Questions | 339 | ||
| Part Five Metabolism | 341 | ||
| Chapter 20 Digestive Enzymes | 342 | ||
| Saliva contains α-amylase and lysozyme | 342 | ||
| Protein and fat digestion start in the stomach | 343 | ||
| The pancreas is a factory for digestive enzymes | 344 | ||
| Fat digestion requires bile salts | 344 | ||
| Some digestive enzymes are anchored to the surface of the microvilli | 346 | ||
| Poorly digestible nutrients cause flatulence | 347 | ||
| Many digestive enzymes are released as inactive precursors | 348 | ||
| Summary | 349 | ||
| Further Reading | 349 | ||
| Questions | 350 | ||
| Chapter 21 Introduction to Metabolic Pathways | 351 | ||
| Alternative substrates can be oxidized in the body | 351 | ||
| Metabolic processes are compartmentalized | 352 | ||
| Free energy changes in metabolic pathways are additive | 352 | ||
| Most metabolic pathways are regulated | 353 | ||
| Feedback inhibition and feedforward stimulation are the most important regulatory principles | 353 | ||
| Metabolism is regulated to ensure homeostasis | 354 | ||
| Inherited enzyme deficiencies cause metabolic diseases | 354 | ||
| Vitamin deficiencies, toxins, and endocrine disorders can disrupt metabolic pathways | 355 | ||
| Summary | 356 | ||
| Questions | 356 | ||
| Chapter 22 Glycolysis, Tricarboxylic Acid Cycle, and Oxidative Phosphorylation | 357 | ||
| Glucose uptake into the cells is regulated | 357 | ||
| Glucose degradation begins in the cytoplasm and ends in the mitochondria | 358 | ||
| Glycolysis begins with ATP-dependent phosphorylations | 359 | ||
| Most glycolytic intermediates have three carbons | 360 | ||
| Phosphofructokinase is the most important regulated enzyme of glycolysis | 361 | ||
| Lactate is produced under anaerobic conditions | 362 | ||
| Pyruvate is decarboxylated to acetyl-CoA in the mitochondria | 363 | ||
| The TCA cycle produces two molecules of carbon dioxide for each acetyl residue | 363 | ||
| Reduced coenzymes are the most important products of the TCA cycle | 366 | ||
| Oxidative pathways are regulated by energy charge and [NADH]/[NAD+] ratio | 366 | ||
| The TCA cycle provides a pool of metabolic intermediates | 367 | ||
| Antiporters transport metabolites across the inner mitochondrial membrane | 369 | ||
| The respiratory chain channels electrons from NADH and FADH2 to molecular oxygen | 370 | ||
| The standard reduction potential is the tendency to donate electrons | 371 | ||
| The respiratory chain contains flavoproteins, iron-sulfur proteins, cytochromes, ubiquinone, and protein-bound copper | 372 | ||
| The respiratory chain contains large multiprotein complexes | 372 | ||
| The respiratory chain creates a proton gradient | 373 | ||
| The proton gradient drives ATP synthesis | 374 | ||
| The efficiency of glucose oxidation is close to 40% | 375 | ||
| Oxidative phosphorylation is limited by the supply of ADP | 376 | ||
| Brown adipose tissue contains an uncoupling protein | 376 | ||
| Mutations in mitochondrial DNA can cause disease | 377 | ||
| Summary | 378 | ||
| Further Reading | 378 | ||
| Questions | 378 | ||
| Chapter 23 Oxygen Deficiency and Oxygen Toxicity | 380 | ||
| Ischemia leads to infarction | 380 | ||
| Oxidative phosphorylation is inhibited by many poisons | 381 | ||
| Hypoxia inducible factor adjusts cell metabolism to hypoxia | 383 | ||
| Reactive oxygen derivatives are formed during oxidative metabolism | 384 | ||
| The respiratory chain is a major source of superoxide | 384 | ||
| Cells have specialized enzymes to destroy reactive oxygen species | 385 | ||
| Free radical formation is affected by energy supply and energy consumption | 386 | ||
| Some vitamins and phytochemicals can scavenge free radicals | 387 | ||
| The NRF2 transcription factor coordinates defenses against reactive oxygen species | 388 | ||
| Phagocytic cells use reactive oxygen species for intracellular killing | 389 | ||
| Summary | 390 | ||
| Further Reading | 390 | ||
| Questions | 390 | ||
| Chapter 24 Carbohydrate Metabolism | 392 | ||
| An adequate blood glucose level must be maintained at all times | 392 | ||
| Gluconeogenesis bypasses the three irreversible reactions of glycolysis | 392 | ||
| Fatty acids cannot be converted into glucose | 393 | ||
| Glycolysis and gluconeogenesis are regulated by hormones | 394 | ||
| Glycolysis and gluconeogenesis are fine tuned by allosteric effectors and hormone-induced enzyme phosphorylations | 394 | ||
| Fructose-2,6-bisphosphate switches the liver from gluconeogenesis to glycolysis | 396 | ||
| Glucokinase is regulated by two regulatory proteins | 396 | ||
| Carbohydrate is stored as glycogen | 398 | ||
| Glycogen is synthesized from glucose | 398 | ||
| Glycogen is degraded by phosphorolytic cleavage | 399 | ||
| Glycogen metabolisSm is regulated by hormones and metabolites | 400 | ||
| Glycogen accumulates in several enzyme deficiencies | 403 | ||
| Fructose is channeled into glycolysis/gluconeogenesis | 404 | ||
| Excess fructose is problematic | 404 | ||
| Excess galactose is channeled into the pathways of glucose metabolism | 406 | ||
| The pentose phosphate pathway supplies NADPH and ribose-5-phosphate | 407 | ||
| Fructose is the principal sugar in seminal fluid | 409 | ||
| Amino sugars and sugar acids are made from glucose | 409 | ||
| Summary | 410 | ||
| Further Reading | 411 | ||
| Questions | 411 | ||
| Chapter 25 The Metabolism of Fatty Acids and Triglycerides | 412 | ||
| Fatty acids differ in chain length and number of double bonds | 412 | ||
| Chylomicrons transport triglycerides from the intestine to other tissues | 414 | ||
| Adipose tissue is specialized for the storage of triglycerides | 415 | ||
| Fat metabolism in adipose tissue is under hormonal control | 416 | ||
| Fatty acids are transported into the mitochondrion | 417 | ||
| β -Oxidation produces acetyl-CoA, NADH, and FADH2 | 418 | ||
| Special fatty acids require special reactions | 419 | ||
| The liver converts excess fatty acids to ketone bodies | 420 | ||
| Fatty acids are synthesized from acetyl-CoA | 423 | ||
| Acetyl-CoA is shuttled into the cytoplasm as citrate | 424 | ||
| Fatty acid synthesis is regulated by hormones and metabolites | 424 | ||
| AMP-Activated protein kinase adapts metabolic pathways to cellular energy status | 426 | ||
| Most fatty acids can be synthesized from palmitate | 427 | ||
| Fatty acids regulate gene expression | 428 | ||
| Polyunsaturated fatty acids can be oxidized nonenzymatically | 429 | ||
| Summary | 429 | ||
| Further Reading | 430 | ||
| Questions | 430 | ||
| Chapter 26 The Metabolism of Membrane Lipids | 432 | ||
| Phosphatidic acid is an intermediate in phosphoglyceride synthesis | 432 | ||
| Phosphoglycerides are remodeled continuously | 432 | ||
| Sphingolipids are synthesized from ceramide | 433 | ||
| Deficiencies of sphingolipid-degrading enzymes cause lipid storage diseases | 434 | ||
| Cholesterol is the least soluble membrane lipid | 438 | ||
| Cholesterol is derived from both endogenous synthesis and the diet | 438 | ||
| Cholesterol biosynthesis is regulated at the level of HMG-CoA reductase | 439 | ||
| Bile acids are synthesized from cholesterol | 440 | ||
| Bile acids are subject to extensive enterohepatic circulation | 441 | ||
| Most gallstones consist of cholesterol | 443 | ||
| Summary | 443 | ||
| Further Reading | 444 | ||
| Questions | 444 | ||
| Chapter 27 Lipid Transport | 445 | ||
| Most plasma lipids are components of lipoproteins | 445 | ||
| Lipoproteins have characteristic lipid and protein compositions | 446 | ||
| Dietary lipids are transported by chylomicrons | 447 | ||
| VLDL is a precursor of LDL | 447 | ||
| LDL is removed by receptor-mediated endocytosis | 449 | ||
| Cholesterol regulates its own metabolism | 450 | ||
| HDL is needed for reverse cholesterol transport | 451 | ||
| Lipoproteins can initiate atherosclerosis | 452 | ||
| Lipoproteins respond to diet and lifestyle | 454 | ||
| Hyperlipoproteinemias are grouped into five phenotypes | 456 | ||
| Type I hyperlipoproteinemia | 457 | ||
| Type II hyperlipoproteinemia | 458 | ||
| Type III hyperlipoproteinemia | 458 | ||
| Type IV hyperlipoproteinemia | 458 | ||
| Type V hyperlipoproteinemia | 459 | ||
| Hyperlipidemias are treated with diet and drugs | 459 | ||
| Summary | 461 | ||
| Further Reading | 461 | ||
| Questions | 462 | ||
| Chapter 28 Amino Acid Metabolism | 463 | ||
| Amino acids can be used for gluconeogenesis and ketogenesis | 463 | ||
| The nitrogen balance indicates the net rate of protein synthesis | 463 | ||
| The amino group of amino acids is released as ammonia | 464 | ||
| Ammonia is detoxified to urea | 465 | ||
| Urea is synthesized in the urea cycle | 465 | ||
| Hyperammonemia can be treated with diet and drugs | 467 | ||
| Some amino acids are closely related to common metabolic intermediates | 470 | ||
| Glycine, serine, and threonine are glucogenic | 470 | ||
| Proline, arginine, ornithine, and histidine are degraded to glutamate | 472 | ||
| Methionine and cysteine are metabolically related | 473 | ||
| Valine, leucine, and isoleucine are degraded by transamination and oxidative decarboxylation | 475 | ||
| Phenylalanine and tyrosine are both glucogenic and ketogenic | 477 | ||
| Melanin is synthesized from tyrosine | 477 | ||
| Lysine and tryptophan have lengthy catabolic pathways | 480 | ||
| The liver is the most important organ of amino acid metabolism | 481 | ||
| Glutamine participates in renal Ł acid-base regulation | 483 | ||
| Summary | 484 | ||
| Further Reading | 484 | ||
| Questions | 485 | ||
| Chapter 29 Metabolism of Iron and Heme | 486 | ||
| Iron is conserved very efficiently in the body | 486 | ||
| Iron uptake by cells is regulated | 487 | ||
| Dietary iron is absorbed in the duodenum | 487 | ||
| Iron deficiency is the most common micronutrient deficiency worldwide | 490 | ||
| Bone marrow and liver are the most important sites of heme synthesis | 491 | ||
| Heme is synthesized from succinyl-CoA and glycine | 492 | ||
| Porphyrias are caused by deficiencies of heme-synthesizing enzymes | 493 | ||
| Heme is degraded to bilirubin | 494 | ||
| Bilirubin is conjugated and excreted by the liver | 495 | ||
| Elevations of serum bilirubin cause jaundice | 496 | ||
| Many diseases can cause jaundice | 497 | ||
| Summary | 499 | ||
| Further Reading | 499 | ||
| Questions | 500 | ||
| Chapter 30 The Metabolism of Purines and Pyrimidines | 501 | ||
| Purine synthesis starts with ribose-5-phosphate | 501 | ||
| Purines are degraded to uric acid | 502 | ||
| Free purine bases can be salvaged | 503 | ||
| Pyrimidines are synthesized from carbamoyl phosphate and aspartate | 503 | ||
| DNA synthesis requires deoxyribonucleotides | 504 | ||
| Many antineoplastic drugs inhibit nucleotide metabolism | 504 | ||
| Uric acid has limited water solubility | 506 | ||
| Hyperuricemia causes gout | 508 | ||
| Abnormalities of purine-metabolizing enzymes can cause gout | 509 | ||
| Gout can be treated with drugs | 509 | ||
| Summary | 510 | ||
| Further Reading | 510 | ||
| Questions | 510 | ||
| Chapter 31 Micronutrients | 511 | ||
| Riboflavin is a precursor of flavin mononucleotide and flavin adenine dinucleotide | 511 | ||
| Niacin is a precursor of NAD and NADP | 512 | ||
| Thiamine deficiency causes weakness and amnesia | 514 | ||
| Vitamin B6 plays a key role in amino acid metabolism | 515 | ||
| Pantothenic acid is a building block of coenzyme a | 516 | ||
| Biotin is a coenzyme in carboxylation reactions | 516 | ||
| Folic acid deficiency causes megaloblastic anemia | 517 | ||
| Vitamin B12 requires intrinsic factor for its absorption | 519 | ||
| Vitamin c is a water-soluble antioxidant | 521 | ||
| Retinol, retinal, and retinoic acid are the active forms of vitamin a | 523 | ||
| Vitamin d is a prohormone | 525 | ||
| Vitamin e prevents lipid oxidation | 526 | ||
| Many vitamins and phytochemicals are antioxidants | 527 | ||
| Vitamin k is required for blood clotting | 528 | ||
| Zinc is a constituent of many enzymes | 528 | ||
| Copper participates in reactions of molecular oxygen | 529 | ||
| Some trace elements serve very specific functions | 530 | ||
| Summary | 531 | ||
| Further Reading | 531 | ||
| Questions | 532 | ||
| Chapter 32 Integration of Metabolism | 533 | ||
| Insulin is released in response to elevated glucose | 533 | ||
| Insulin stimulates the utilization of nutrients | 534 | ||
| Protein synthesis is coordinated by the mTOR complex | 535 | ||
| Glucagon maintains the blood glucose level | 536 | ||
| Catecholamines mediate the flight-or-fight response | 536 | ||
| Glucocorticoids are released in chronic stress | 537 | ||
| Energy is expended continuously | 538 | ||
| Stored fat and glycogen are degraded between meals | 539 | ||
| Adipose tissue is the most important energy depot | 540 | ||
| The liver converts dietary carbohydrates to glycogen and fat after a meal | 541 | ||
| The liver maintains the blood glucose level during fasting | 541 | ||
| Ketone bodies provide lipid-based energy during fasting | 544 | ||
| Obesity is common in all affluent countries | 544 | ||
| Appetite control is the most important determinant of obesity | 546 | ||
| Obesity is related to insulin resistance | 547 | ||
| Diabetes is caused by insulin deficiency or insulin resistance | 549 | ||
| In diabetes, metabolism is regulated as in starvation | 550 | ||
| Diabetes is diagnosed with laboratory tests | 551 | ||
| Diabetes leads to late complications | 552 | ||
| Many drugs are available for diabetes treatment | 553 | ||
| Contracting muscle has three energy sources | 553 | ||
| Creatine Phosphate | 553 | ||
| Anaerobic Glycolysis | 553 | ||
| Oxidative Metabolism | 554 | ||
| Catecholamines coordinate metabolism during exercise | 555 | ||
| Physical exercise leads to adaptive changes | 557 | ||
| Ethanol is metabolized to acetyl-CoA in the liver | 558 | ||
| Liver metabolism is deranged by alcohol | 560 | ||
| Alcohol abuse leads to fatty liver and liver cirrhosis | 561 | ||
| Most “diseases of civilization” are caused by aberrant lifestyles | 561 | ||
| Aging is the greatest challenge for medical research | 564 | ||
| Antiaging treatments are being investigated | 565 | ||
| Summary | 566 | ||
| Further Reading | 566 | ||
| Questions | 567 | ||
| Answers to questions | 569 | ||
| Chapter 1 | 569 | ||
| Chapter 2 | 569 | ||
| Chapter 3 | 569 | ||
| Chapter 4 | 569 | ||
| Chapter 5 | 569 | ||
| Chapter 6 | 569 | ||
| Chapter 7 | 569 | ||
| Chapter 8 | 569 | ||
| Chapter 9 | 569 | ||
| Chapter 10 | 569 | ||
| Chapter 11 | 569 | ||
| Chapter 12 | 569 | ||
| Chapter 13 | 569 | ||
| Chapter 14 | 569 | ||
| Chapter 15 | 569 | ||
| Chapter 16 | 569 | ||
| Chapter 17 | 569 | ||
| Chapter 18 | 569 | ||
| Chapter 19 | 569 | ||
| Chapter 20 | 569 | ||
| Chapter 21 | 569 | ||
| Chapter 22 | 569 | ||
| Chapter 23 | 569 | ||
| Chapter 24 | 569 | ||
| Chapter 25 | 569 | ||
| Chapter 26 | 569 | ||
| Chapter 27 | 569 | ||
| Chapter 28 | 570 | ||
| Chapter 29 | 570 | ||
| Chapter 30 | 570 | ||
| Chapter 31 | 570 | ||
| Chapter 32 | 570 | ||
| Glossary | 571 | ||
| Credits | 590 | ||
| Index | 591 | ||
| Inside Back cover | ES3 |