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

Km and Vmax Can Be Determined Graphically

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

Zero-Order Reactions

Kcat/Km 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

Bacteria Can Exchange Genes by...