Amazon no longer offers textbook rentals. We do!

Principles of Medical Biochemistry; with STUDENT CONSULT Access

by: Meisenberg & Simmons

Principles of Medical Biochemistry; with STUDENT CONSULT Access

by: Meisenberg & Simmons

ISBN 13:
9780323029421
ISBN 10:
0323029426
Edition: 2nd
Format: Paperback
Copyright: 01/27/2006
Publisher: HARCOURT HEALTH SCIENCES-MOSBY
Newer Edition

Rent

Sorry, this item is currently unavailable on Knetbooks.com

Click the link below to purchase this eBook from our trusted partner, eCampus.com.

View eBook

Note: Supplemental materials are not guaranteed with Rental or Used book purchases.

Extend or Purchase Your Rental at Any Time

Need to keep your rental past your due date? At any time before your due date you can extend or purchase your rental through your account.

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

PART ONE PRINCIPLES OF MOLECULAR STRUCTURE AND FUNCTION

(68)

Introduction to Biomolecules

(16)

Water Is the Solvent of Life

(1)

Water Contains Hydronium Ions and Hydroxyl Ions

(1)

Ionizable Groups Are Characterized by Their pK Values

(1)

Bonds Are Formed by Reactions between Functional Groups

(1)

Isomeric Forms Are Common in Biomolecules

(1)

The Properties of Biomolecules Are Determined by Their Noncovalent Interactions

(2)

Triglycerides Consist of Fatty Acids and Glycerol

(1)

Monosaccharides Are Polyalcohols with a Keto Group or an Aldehyde Group

(1)

Monosaccharides Form Ring Structures

(1)

Complex Carbohydrates Are Formed by Glycosidic Bonds

(1)

Polypeptides Are Formed from Amino Acids

(2)

Nucleic Acids Are Formed from Nucleotides

(1)

Most Biomolecules Are Polymers

(4)

Summary

(2)

Introduction to Protein Structure

(14)

Amino Acids Are Zwitterions

(1)

Amino Acid Side Chains Form Many Noncovalent Interactions

(2)

Peptide Bonds and Disulfide Bonds Form the Primary Structure of Proteins

(1)

Proteins Can Fold Themselves into Many Different Shapes

(2)

The α Helix and β-Pleated Sheet Are the Most Common Secondary Structures in Proteins

(1)

Globular Proteins Have a Hydrophobic Core

(1)

The Higher Order Structure Forms While the Polypeptide Is Being Synthesized

(1)

Proteins Lose Their Biological Activities When Their Higher Order Structure Is Destroyed

(1)

The Solubility of Proteins Depends on pH and Salt Concentration

(1)

Proteins Absorb Ultraviolet Radiation

(1)

Proteins Can Be Separated by Their Charge or Their Molecular Weight

(5)

Summary

(3)

Oxygen Transporters: Hemoglobin and Myoglobin

(10)

The Heme Group Is the Oxygen-Binding Site of Hemoglobin and Myoglobin

(1)

Myoglobin Is a Tightly Packed Globular Protein

(1)

The Red Blood Cells Are Specialized for Oxygen Transport

(1)

The Hemoglobins Are Tetrameric Proteins

(1)

Oxygenated and Deoxygenated Hemoglobin Have Different Quaternary Structures

(1)

Oxygen Binding to Hemoglobin Is Cooperative

(1)

2,3-Bisphosphoglycerate Is a Negative Allosteric Effector of Oxygen Binding to Hemoglobin

(1)

Fetal Hemoglobin Has a Higher Oxygen Binding Affinity than Does Adult Hemoglobin

(1)

The Bohr Effect Facilitates Oxygen Delivery

(1)

Most Carbon Dioxide Is Transported as Bicarbonate

(1)

Anemia Is Commonly Seen in Clinical Practice

(1)

Methemoglobin Is a Nonfunctional Oxidized Form of Hemoglobin

(1)

Carbon Monoxide Competes with Oxygen for Binding to the Heme Iron

(3)

Summary

(2)

Enzymatic Reactions

(18)

The Equilibrium Constant Describes the Equilibrium of the Reaction

(1)

The Free Energy Change Is the Driving Force for Chemical Reactions

(1)

The Standard Free Energy Change Determines the Equilibrium

(1)

Enzymes Are Both Powerful and Selective

(1)

The Substrate Must Bind to Its Enzyme before the Reaction Can Proceed

(1)

Rate Constants Are Useful for Describing Reaction Rates

(1)

Enzymes Decrease the Free Energy of Activation

(1)

Many Enzymatic Reactions Can Be Described by Michaelis-Menten Kinetics

(2)

Km and Vmax Can Be Determined Graphically

(1)

Substrate Half-Life Can Be Determined for First-Order but Not Zero-Order Reactions

(1)

Kcat/Km Predicts the Enzyme Activity at Low Substrate Concentration

(1)

Allosteric Enzymes Do Not Conform to Michaelis-Menten Kinetics

(1)

Enzyme Activity Depends on Temperature and pH

(1)

Different Types of Reversible Enzyme Inhibition Can Be Distinguished Kinetically

(1)

Covalent Modification Can Inhibit Enzymes Irreversibly

(1)

Enzymes Are Classified According to Their Reaction Type

(1)

Enzymes Stabilize the Transition State

(1)

Chymotrypsin Forms a Transient Covalent Bond during Catalysis

(4)

Summary

(4)

Coenzymes

(8)

ATP Has Two Energy-Rich Bonds

(2)

ATP Is the Phosphate Donor in Phosphorylation Reactions

(1)

ATP Hydrolysis Drives Endergonic Reactions

(1)

Cells Always Try to Maintain a High Energy Charge

(1)

Dehydrogenase Reactions Require Specialized Coenzymes

(1)

Coenzyme A Activates Organic Acids

(1)

S-Adenosyl Methionine Donates Methyl Groups

(2)

Many Enzymes Require a Metal Ion

(2)

Summary

(1)

PART TWO GENETIC INFORMATION: DNA, RNA, AND PROTEIN SYNTHESIS

(128)

DNA, RNA, and Protein Synthesis

(32)

All Living Organisms Use DNA as Their Genetic Databank

(1)

DNA Contains Four Bases

(1)

DNA Forms a Double Helix

(1)

DNA Can Be Denatured

(1)

DNA Is Supercoiled

(1)

DNA Replication Is Semiconservative

(1)

DNA Is Synthesized by DNA Polymerases

(1)

Bacterial DNA Polymerases Have Exonuclease Activities

(2)

Unwinding Proteins Present a Single-Stranded Template to the DNA Polymerases

(1)

One of the New DNA Strands Is Synthesized Discontinuously

(2)

RNA Plays Key Roles in Gene Expression

(1)

The σ Subunit Recognizes Promoters

(1)

DNA Is Faithfully Copied Into RNA

(1)

Transcription Is Terminated When the RNA Forms a Hairpin Loop

(1)

Transcription Can Be Inhibited by Drugs

(2)

Some RNAs Are Chemically Modified after Transcription

(1)

The Genetic Code Defines the Relationship between the Base Sequence of the Messenger RNA and the Amino Acid Sequence of the Polypeptide

(2)

Transfer RNA Is the Adapter Molecule in Protein Synthesis

(1)

Amino Acids Are Activated by an Ester Bond with the 3'-Terminus of the Transfer RNA

(1)

Many Transfer RNAs Recognize More than One Codon

(1)

Ribosomes Are the Workbenches for Protein Synthesis

(2)

The Initiation Complex Brings Ribosome, Messenger RNA, and Initiator-Transfer RNA Together

(1)

Polypeptides Grow Stepwise from the Amino Terminus to the Carboxyl Terminus

(1)

Protein Synthesis Is Energetically Expensive

(1)

Many Antibiotics Inhibit Protein Synthesis

(2)

Gene Expression Is Tightly Regulated

(1)

A Repressor Protein Regulates the Transcription of the lac Operon in Escherichia coli

(1)

Anabolic Operons Are Repressed by the End Product of the Pathway

(1)

Glucose Regulates the Transcription of Many Catabolic Operons

(1)

Transcriptional Regulation Depends on DNA-Binding Proteins

(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

Amazon no longer offers textbook rentals. We do!

Principles of Medical Biochemistry; with STUDENT CONSULT Access

Principles of Medical Biochemistry; with STUDENT CONSULT Access

9780323029421

0323029426

Summary

Table of Contents

Supplemental Materials

Write a Review

Amazon no longer offers textbook rentals. We do!

Principles of Medical Biochemistry; with STUDENT CONSULT Access

Principles of Medical Biochemistry; with STUDENT CONSULT Access

9780323029421

0323029426

Summary

Table of Contents

Supplemental Materials

Write a Review

Related Products