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Part ONE PRINCIPLES OF MOLECULAR STRUCTURE AND FUNCTION 1
Chapter 1 INTRODUCTION TO BIOMOLECULES Water Is the Solvent of Life Water Contains Hydronium Ions and Hydroxyl Ions Ionizable Groups Are Characterized by Their pK Values The Blood pH is Tightly Regulated Acidosis and Alkalosis Are Common in Clinical Practice Bonds Are Formed by Reactions between Functional Groups Isomeric Forms Are Common in Biomolecules Properties of Biomolecules Are Determined by Their Noncovalent Interactions Triglycerides Consist of Fatty Acids and Glycerol Monosaccharides Are Polyalcohols with a Keto Group or an Aldehyde Group Monosaccharides Form Ring Structures Complex Carbohydrates Are Formed by Glycosidic Bonds Polypeptides Are Formed from Amino Acids Nucleic Acids Are Formed from Nucleotides Most Biomolecules Are Polymers Summary
Chapter 2 INTRODUCTION TO PROTEIN STRUCTURE Amino Acids Are Zwitterions Amino Acid Side Chains Form Many Noncovalent Interactions Peptide Bonds and Disulfide Bonds Form the Primary Structure of Proteins Proteins Can Fold Themselves into Many Shapes a-Helix and ß-Pleated Sheet Are the Most Common Secondary Structures in Proteins Globular Proteins Have a Hydrophobic Core Proteins Lose Their Biological Activities When Their Higher-Order Structure Is Destroyed The Solubility of Proteins Depends on pH and Salt Concentration Proteins Absorb Ultraviolet Radiation Proteins Can Be Separated by Their Charge or Their Molecular Weight Abnormal Protein Aggregates Can Cause Disease Neurodegenerative Diseases Are Caused by Protein Aggregates Protein Misfolding Can Be Contagious Summary
Chapter 3 OXYGEN TRANSPORTERS: HEMOGLOBIN AND MYOGLOBIN The Heme Group Is the Oxygen-Binding Site of Hemoglobin and Myoglobin Myoglobin Is a Tightly Packed Globular Protein Red Blood Cells Are Specialized for Oxygen Transport The Hemoglobins Are Tetrameric Proteins Oxygenated and Deoxygenated Hemoglobin Have Different Quaternary Structures Oxygen Binding to Hemoglobin Is Cooperative 2,3-Bisphosphoglycerate Is a Negative Allosteric Effector of Oxygen Binding to Hemoglobin Fetal Hemoglobin Has a Higher Oxygen-Binding Affinity than Does Adult Hemoglobin The Bohr Effect Facilitates Oxygen Delivery Most Carbon Dioxide Is Transported as Bicarbonate Summary 38
Chapter 4 ENZYMATIC REACTIONS 39 The Equilibrium Constant Describes the Equilibrium of the Reaction The Free Energy Change Is the Driving Force for Chemical Reactions The Standard Free Energy Change Determines the Equilibrium Enzymes Are Both Powerful and Selective The Substrate Must Bind to Its Enzyme before the Reaction Can Proceed Rate Constants Are Useful for Describing Reaction Rates Enzymes Decrease the Free Energy of Activation Many Enzymatic Reactions Can Be Described by Michaelis-Menten Kinetics K m and V max Can Be Determined Graphically Substrate Half-Life Can Be Determined for First-Order but Not Zero-Order Reactions K cat/ K m Predicts the Enzyme Activity at Low Substrate Concentration Allosteric Enzymes Do Not Conform to Michaelis-Menten Kinetics Enzyme Activity Depends on Temperature and pH Different Types of Reversible Enzyme Inhibition Can Be Distinguished Kinetically Enzymes Stabilize the Transition State Chymotrypsin Forms a Transient Covalent Bond during Catalysis Summary
Chapter 5 COENZYMES Enzymes Are Classified According to Their Reaction Type Adenosine Triphosphate Has Two Energy-Rich Bonds ATP Is the Phosphate Donor in Phosphorylation Reactions ATP Hydrolysis Drives Endergonic Reactions Cells Always Try to Maintain a High Energy Charge Dehydrogenase Reactions Require Specialized Coenzymes Coenzyme A Activates Organic Acids S-Adenosyl Methionine Donates Methyl Groups Many Enzymes Require a Metal Ion Summary
Part TWO GENETIC INFORMATION: DNA, RNA, AND PROTEIN SYNTHESIS
Chapter 6 DNA, RNA, AND PROTEIN SYNTHESIS All Living Organisms Use DNA as Their Genetic Databank DNA Contains Four Bases DNA Forms a Double Helix DNA Can Be Denatured DNA Is Supercoiled DNA Replication Is Semiconservative DNA Is Synthesized by DNA Polymerases DNA Polymerases Have Exonuclease Activities Unwinding Proteins Present a Single-Stranded Template to the DNA Polymerases One of the New DNA Strands Is Synthesized Discontinuously RNA Plays Key Roles in Gene Expression The S Subunit Recognizes Promoters DNA Is Faithfully Copied into RNA Some RNAs Are Chemically Modified after Transcription The Genetic Code Defines the Structural Relationship between mRNA and Polypeptide Transfer RNA Is the Adapter Molecule in Protein Synthesis Amino Acids Are Activated by an Ester Bond with the 3'' Terminus of the tRNA Many Transfer RNAs Recognize More than One Codon Ribosomes Are the Workbenches for Protein Synthesis The Initiation Complex Brings Together Ribosome, Messenger RNA, and Initiator tRNA Polypeptides Grow Stepwise from the Amino Terminus to the Carboxyl Terminus Protein Synthesis Is Energetically Expensive Gene Expression Is Tightly Regulated A Repressor Protein Regulates Transcription of the lac Operon in E. coli Anabolic Operons Are Repressed by the End Product of the Pathway Glucose Regulates the Transcription of Many Catabolic Operons Transcriptional Regulation Depends on DNA-Binding Proteins Summary
Chapter 7 THE HUMAN GENOME Chromatin Consists of DNA and Histones The Nucleosome Is the Structural Unit of Chromatin Covalent Histone Modifications Regulate DNA Replication and Transcription DNA Methylation Silences Genes All Eukaryotic Chromosomes Have a Centromere, Telomeres, and Replication Origins Telomerase Is Required (but Not Sufficient) for Immortality Eukaryotic DNA Replication Requires Three DNA Polymerases Most Human DNA Does Not Code for Proteins Gene Families Originate by Gene Duplication The Genome Contains Many Tandem Repeats Some DNA Sequences Are Copies of Functional RNAs Many Repetitive DNA Sequences Are (or Were) Mobile L1 Elements Encode a Reverse Transcriptase Alu Sequences Spread with the Help of L1 Reverse Transcriptase Mobile Elements Are Dangerous Humans Have Approximately 20,000 Genes Transcriptional Initiation Requires General Transcription Factors Genes Are Surrounded by Regulatory Sites Gene Expression Is Regulated by DNA-Binding Proteins Long Non-coding RNAs Play Roles in Gene Expression mRNA Processing Starts during Transcription Translational Initiation Requires Many Initiation Factors mRNA Processing and Translation Are Often Regulated Small RNA Molecules Inhibit Gene Expression Mitochondria Have Their Own DNA Human Genomes Are Very Diverse Human Genomes Have Many Low-Frequency Copy Number Variations Summary
Chapter 8 PROTEIN TARGETING AND PROTEOSTASIS A Signal Sequence Directs Polypeptides to the Endoplasmic Reticulum Glycoproteins Are Processed in the Secretory Pathway The Endocytic Pathway Brings Proteins into the Cell Lysosomes Are Organelles of Intracellular Digestion Autophagy Recycles Cellular Proteins and Organelles Poorly Folded Proteins Are Either Repaired or Destroyed Ubiquitin Markes Proteins for Destruction The Proteostatic System Protects Cells from Abnormal Proteins Summary
Chapter 9 INTRODUCTION TO GENETIC DISEASES Four Types of Genetic Disease Mutations Occur in the Germline and in Somatic Cells Mutations Are an Important Cause of Poor Health Small Mutations Lead to Abnormal Proteins Most Mutations Are Caused by Replication Errors Mutations Can Be Induced by Radiation and Chemicals Mismatch Repair Corrects Replication Errors Missing Bases and Abnormal Bases Need to Be Replaced Nucleotide Excision Repair Removes Bulky Lesions Repair of DNA Double-Strand Breaks Is Difficult Hemoglobin Genes Form Two Gene Clusters Many Point Mutations in Hemoglobin Genes Are Known Sickle Cell Disease Is Caused by a Point Mutation in the b-Chain Gene SA Heterozygotes Are Protected from Tropical Malaria a-Thalassemia Is Most Often Caused by Large Deletions Many Different Mutations Can Cause ß-Thalassemia Fetal Hemoglobin Protects from the Effects of ß-Thalassemia and Sickle Cell Disease Summary
Chapter 10 VIRUSES Viruses Can Replicate Only in a Host Cell Bacteriophage T4 Destroys Its Host Cell DNA Viruses Substitute Their Own DNA for the Host Cell DNA ? Phage Can Integrate Its DNA into the Host Cell Chromosome RNA Viruses Require an RNA-Dependent RNA Polymerase Retroviruses Replicate Through a DNA Intermediate Plasmids Are Small "Accessory Chromosomes" or "Symbiotic Viruses" of Bacteria