Biochemistry 9th Edition by Lubert Stryer, ISBN-13: 978-1319114671

Part I THE MOLECULAR DESIGN OF LIFE

Chapter 1 Biochemistry: An Evolving Science

1.1 Biochemical Unity Underlies Biological Diversity

1.2 DNA Illustrates the Interplay Between Form and Function

DNA is constructed from four building blocks

Two single strands of DNA combine to form a double helix

DNA structure explains heredity and the storage of information

1.3 Concepts from Chemistry Explain the Properties of Biological Molecules

The formation of the DNA double helix as a key example

The double helix can form from its component strands

Covalent and noncovalent bonds are important for the structure and stability of biological molecules

The double helix is an expression of the rules of chemistry

The laws of thermodynamics govern the behavior of biochemical systems

Heat is released in the formation of the double helix

Acid–base reactions are central in many biochemical processes

Acid–base reactions can disrupt the double helix

Buffers regulate pH in organisms and in the laboratory

1.4 The Genomic Revolution Is Transforming Biochemistry, Medicine, and Other Fields

Genome sequencing has transformed biochemistry and other fields

Environmental factors influence human biochemistry

Genome sequences encode proteins and patterns of expression

APPENDIX Visualizing Molecular Structures: Small Molecules

APPENDIX Functional Groups

Chapter 2 Protein Composition and Structure

2.1 Proteins Are Built from a Repertoire of 20 Amino Acids

2.2 Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains

Proteins have unique amino acid sequences specified by genes

Polypeptide chains are flexible yet conformationally restricted

2.3 Secondary Structure: Polypeptide Chains Can Fold into Regular Structures Such As the Alpha Helix, the Beta Sheet, and Turns and Loops

The alpha helix is a coiled structure stabilized by intrachain hydrogen bonds

Beta sheets are stabilized by hydrogen bonding between polypeptide strands

Polypeptide chains can change direction by making reverse turns and loops

2.4 Tertiary Structure: Proteins Can Fold into Globular or Fibrous Structures

Fibrous proteins provide structural support for cells and tissues

2.5 Quaternary Structure: Polypeptide Chains Can Assemble into Multisubunit Structures

2.6 The Amino Acid Sequence of a Protein Determines Its Three-Dimensional Structure

Amino acids have different propensities for forming 〈 helices, ® sheets, and turns

Protein folding is a highly cooperative process

Proteins fold by progressive stabilization of intermediates rather than by random search

Prediction of three-dimensional structure from sequence remains a great challenge

Some proteins are inherently unstructured and can exist in multiple conformations

Protein misfolding and aggregation are associated with some neurological diseases

Posttranslational modifications confer new capabilities to proteins

APPENDIX Visualizing Molecular Structures: Proteins

Chapter 3 Exploring Proteins and Proteomes

3.1 The Purification of Proteins Is an Essential First Step in Understanding Their Function

The assay: How do we recognize the protein that we are looking for?

Proteins must be released from the cell to be purified

Proteins can be purified according to solubility, size, charge, and binding affinity

Proteins can be separated by gel electrophoresis and displayed

A protein purification scheme can be quantitatively evaluated

Ultracentrifugation is valuable for separating biomolecules and determining their masses

Protein purification can be made easier with the use of recombinant DNA technology

3.2 Immunology Provides Important Techniques with Which to Investigate Proteins

Antibodies to specific proteins can be generated

Monoclonal antibodies with virtually any desired specificity can be readily prepared

Proteins can be detected and quantified by using an enzyme-linked immunosorbent assay

Western blotting permits the detection of proteins separated by gel electrophoresis

Co-immunoprecipitation enables the identification of binding partners of a protein

Fluorescent markers make the visualization of proteins in the cell possible

3.3 Mass Spectrometry Is a Powerful Technique for the Identification of Peptides and Proteins

Peptides can be sequenced by mass spectrometry

Proteins can be specifically cleaved into small peptides to facilitate analysis

Genomic and proteomic methods are complementary

The amino acid sequence of a protein provides valuable information

Individual proteins can be identified by mass spectrometry

3.4 Peptides Can Be Synthesized by Automated Solid-Phase Methods

3.5 Three-Dimensional Protein Structure Can Be Determined by X-ray Crystallography, NMR Spectroscopy, and Cryo-Electron Microscopy

X-ray crystallography reveals three-dimensional structure in atomic detail

Nuclear magnetic resonance spectroscopy can reveal the structures of proteins in solution

Cryo-electron microscopy is an emerging method of protein structure determination

APPENDIX Problem-Solving Strategies

Chapter 4 DNA, RNA, and the Flow of Genetic Information

4.1 A Nucleic Acid Consists of Four Kinds of Bases Linked to a Sugar–Phosphate Backbone

RNA and DNA differ in the sugar component and one of the bases

Nucleotides are the monomeric units of nucleic acids

DNA molecules are very long and have directionality

4.2 A Pair of Nucleic Acid Strands with Complementary Sequences Can Form a Double-Helical Structure

The double helix is stabilized by hydrogen bonds and van der Waals interactions

DNA can assume a variety of structural forms

Some DNA molecules are circular and supercoiled

Single-stranded nucleic acids can adopt elaborate structures

4.3 The Double Helix Facilitates the Accurate Transmission of Hereditary Information

Differences in DNA density established the validity of the semiconservative replication hypothesis

The double helix can be reversibly melted

Unusual circular DNA exists in the eukaryotic nucleus

4.4 DNA Is Replicated by Polymerases That Take Instructions from Templates

DNA polymerase catalyzes phosphodiester-bridge formation

The genes of some viruses are made of RNA

4.5 Gene Expression Is the Transformation of DNA Information into Functional Molecules

Several kinds of RNA play key roles in gene expression

All cellular RNA is synthesized by RNA polymerases

RNA polymerases take instructions from DNA templates

Transcription begins near promoter sites and ends at terminator sites

Transfer RNAs are the adaptor molecules in protein synthesis

4.6 Amino Acids Are Encoded by Groups of Three Bases Starting from a Fixed Point

Major features of the genetic code

Messenger RNA contains start and stop signals for protein synthesis

The genetic code is nearly universal

4.7 Most Eukaryotic Genes Are Mosaics of Introns and Exons

RNA processing generates mature RNA

Many exons encode protein domains

APPENDIX Problem-Solving Strategies

Chapter 5 Exploring Genes and Genomes

5.1 The Exploration of Genes Relies on Key Tools

Restriction enzymes split DNA into specific fragments

Restriction fragments can be separated by gel electrophoresis and visualized

DNA can be sequenced by controlled termination of replication

DNA probes and genes can be synthesized by automated solid-phase methods

Selected DNA sequences can be greatly amplified by the polymerase chain reaction

PCR is a powerful technique in medical diagnostics, forensics, and studies of molecular evolution

The tools for recombinant DNA technology have been used to identify disease-causing mutations

5.2 Recombinant DNA Technology Has Revolutionized All Aspects of Biology

Restriction enzymes and DNA ligase are key tools in forming recombinant DNA molecules

Plasmids and ⎣ phage are choice vectors for DNA cloning in bacteria

Bacterial and yeast artificial chromosomes

Specific genes can be cloned from digests of genomic DNA

Complementary DNA prepared from mRNA can be expressed in host cells

Proteins with new functions can be created through directed changes in DNA

Recombinant methods enable the exploration of the functional effects of disease-causing mutations

5.3 Complete Genomes Have Been Sequenced and Analyzed

The genomes of organisms ranging from bacteria to multicellular eukaryotes have been sequenced

The sequence of the human genome has been completed

Next-generation sequencing methods enable the rapid determination of a complete genome sequence

Comparative genomics has become a powerful research tool

5.4 Eukaryotic Genes Can Be Quantitated and Manipulated with Considerable Precision

Gene-expression levels can be comprehensively examined

New genes inserted into eukaryotic cells can be efficiently expressed

Transgenic animals harbor and express genes introduced into their germ lines

Gene disruption and genome editing provide clues to gene function and opportunities for new therapies

RNA interference provides an additional tool for disrupting gene expression

Tumor-inducing plasmids can be used to introduce new genes into plant cells

Human gene therapy holds great promise for medicine

APPENDIX Biochemistry in Focus: Improved biofuel production from genetically-engineered algae

Chapter 6 Exploring Evolution and Bioinformatics

6.1 Homologs Are Descended from a Common Ancestor

6.2 Statistical Analysis of Sequence Alignments Can Detect Homology

The statistical significance of alignments can be estimated by shuffling

Distant evolutionary relationships can be detected through the use of substitution matrices

Databases can be searched to identify homologous sequences

6.3 Examination of Three-Dimensional Structure Enhances Our Understanding of Evolutionary Relationships

Tertiary structure is more conserved than primary structure

Knowledge of three-dimensional structures can aid in the evaluation of sequence alignments

Repeated motifs can be detected by aligning sequences with themselves

Convergent evolution illustrates common solutions to biochemical challenges

Comparison of RNA sequences can be a source of insight into RNA secondary structures

6.4 Evolutionary Trees Can Be Constructed on the Basis of Sequence Information

Horizontal gene transfer events may explain unexpected branches of the evolutionary tree

6.5 Modern Techniques Make the Experimental Exploration of Evolution Possible

Ancient DNA can sometimes be amplified and sequenced

Molecular evolution can be examined experimentally

APPENDIX Biochemistry in Focus: Using sequence alignments to identify functionally important residues

APPENDIX Problem-Solving Strategies

Chapter 7 Hemoglobin: Portrait of a Protein in Action

7.1 Binding of Oxygen by Heme Iron

Changes in heme electronic structure upon oxygen binding are the basis for functional imaging studies

The structure of myoglobin prevents the release of reactive oxygen species

Human hemoglobin is an assembly of four myoglobin-like subunits

7.2 Hemoglobin Binds Oxygen Cooperatively

Oxygen binding markedly changes the quaternary structure of hemoglobin

Hemoglobin cooperativity can be potentially explained by several models

Structural changes at the heme groups are transmitted to the 〈1®1–〈2®2 interface

2,3-Bisphosphoglycerate in red cells is crucial in determining the oxygen affinity of hemoglobin

Carbon monoxide can disrupt oxygen transport by hemoglobin

7.3 Hydrogen Ions and Carbon Dioxide Promote the Release of Oxygen: The Bohr Effect

7.4 Mutations in Genes Encoding Hemoglobin Subunits Can Result in Disease

Sickle-cell anemia results from the aggregation of mutated deoxyhemoglobin molecules

Thalassemia is caused by an imbalanced production of hemoglobin chains

The accumulation of free alpha-hemoglobin chains is prevented

Additional globins are encoded in the human genome

APPENDIX Binding Models Can Be Formulated in Quantitative Terms: The Hill Plot and the Concerted Model

APPENDIX Biochemistry in Focus: A potential antidote for carbon monoxide poisoning?

Chapter 8 Enzymes: Basic Concepts and Kinetics

8.1 Enzymes are Powerful and Highly Specific Catalysts

Many enzymes require cofactors for activity

Enzymes can transform energy from one form into another

8.2 Gibbs Free Energy Is a Useful Thermodynamic Function for Understanding Enzymes

The free-energy change provides information about the spontaneity but not the rate of a reaction

The standard free-energy change of a reaction is related to the equilibrium constant

Enzymes alter only the reaction rate and not the reaction equilibrium

8.3 Enzymes Accelerate Reactions by Facilitating the Formation of the Transition State

The formation of an enzyme–substrate complex is the first step in enzymatic catalysis

The active sites of enzymes have some common features

The binding energy between enzyme and substrate is important for catalysis

8.4 The Michaelis–Menten Model Accounts for the Kinetic Properties of Many Enzymes

Kinetics is the study of reaction rates

The steady-state assumption facilitates a description of enzyme kinetics

Variations in KM can have physiological consequences

KM and Vmax values can be determined by several means

KM and Vmax values are important enzyme characteristics

kcat/KM is a measure of catalytic efficiency

Most biochemical reactions include multiple substrates

Allosteric enzymes do not obey Michaelis–Menten kinetics

8.5 Enzymes Can Be Inhibited by Specific Molecules

The different types of reversible inhibitors are kinetically distinguishable

Irreversible inhibitors can be used to map the active site

Penicillin irreversibly inactivates a key enzyme in bacterial cell-wall synthesis

Transition-state analogs are potent inhibitors of enzymes

Enzymes have impact outside the laboratory or clinic

8.6 Enzymes Can Be Studied One Molecule at a Time

APPENDIX Enzymes are Classified on the Basis of the Types of Reactions That They Catalyze

APPENDIX Problem-Solving Strategies

APPENDIX Biochemistry in Focus: The effect of temperature rate on enzyme-catalyzed reactions and the coloring of Siamese cats

Chapter 9 Catalytic Strategies

9.1 Proteases Facilitate a Fundamentally Difficult Reaction

Chymotrypsin possesses a highly reactive serine residue

Chymotrypsin action proceeds in two steps linked by a covalently bound intermediate

Serine is part of a catalytic triad that also includes histidine and aspartate

Catalytic triads are found in other hydrolytic enzymes

The catalytic triad has been dissected by site-directed mutagenesis

Cysteine, aspartyl, and metalloproteases are other major classes of peptide-cleaving enzymes

Protease inhibitors are important drugs

9.2 Carbonic Anhydrases Make a Fast Reaction Faster

Carbonic anhydrase contains a bound zinc ion essential for catalytic activity

Catalysis entails zinc activation of a water molecule

A proton shuttle facilitates rapid regeneration of the active form of the enzyme

9.3 Restriction Enzymes Catalyze Highly Specific DNA-Cleavage Reactions

Cleavage is by in-line displacement of 3′-oxygen from phosphorus by magnesium-activated water

Restriction enzymes require magnesium for catalytic activity

The complete catalytic apparatus is assembled only within complexes of cognate DNA molecules, ensuring specificity

Host-cell DNA is protected by the addition of methyl groups to specific bases

Type II restriction enzymes have a catalytic core in common and are probably related by horizontal gene transfer

9.4 Myosins Harness Changes in Enzyme Conformation to Couple ATP Hydrolysis to Mechanical Work

ATP hydrolysis proceeds by the attack of water on the gamma phosphoryl group

Formation of the transition state for ATP hydrolysis is associated with a substantial conformational change

The altered conformation of myosin persists for a substantial period of time

Scientists can watch single molecules of myosin move

Myosins are a family of enzymes containing P-loop structures

APPENDIX Problem-Solving Strategies

Chapter 10 Regulatory Strategies

10.1 Aspartate Transcarbamoylase Is Allosterically Inhibited by the End Product of Its Pathway

Allosterically regulated enzymes do not follow Michaelis–Menten kinetics

ATCase consists of separable catalytic and regulatory subunits

Allosteric interactions in ATCase are mediated by large changes in quaternary structure

Allosteric regulators modulate the T-to-R equilibrium

10.2 Isozymes Provide a Means of Regulation Specific to Distinct Tissues and Developmental Stages

10.3 Covalent Modification Is a Means of Regulating Enzyme Activity

Kinases and phosphatases control the extent of protein phosphorylation

Phosphorylation is a highly effective means of regulating the activities of target proteins

Cyclic AMP activates protein kinase A by altering the quaternary structure

Mutations in protein kinase A can cause Cushing Syndrome

Exercise modifies the phosphorylation of many proteins

10.4 Many Enzymes Are Activated by Specific Proteolytic Cleavage

Chymotrypsinogen is activated by specific cleavage of a single peptide bond

Proteolytic activation of chymotrypsinogen leads to the formation of a substrate-binding site

The generation of trypsin from trypsinogen leads to the activation of other zymogens

Some proteolytic enzymes have specific inhibitors

Serpins can be degraded by a unique enzyme

Blood clotting is accomplished by a cascade of zymogen activations

Prothrombin must bind to Ca2+ to be converted to thrombin

Fibrinogen is converted by thrombin into a fibrin clot

Vitamin K is required for the formation of ©-carboxyglutamate

The clotting process must be precisely regulated

Hemophilia revealed an early step in clotting

APPENDIX Biochemistry in Focus: Phosphoribosylpyrophosphate synthetase-induced gout

APPENDIX Problem-Solving Strategies

Chapter 11 Carbohydrates

11.1 Monosaccharides Are the Simplest Carbohydrates

Many common sugars exist in cyclic forms

Pyranose and furanose rings can assume different conformations

Glucose is a reducing sugar

Monosaccharides are joined to alcohols and amines through glycosidic bonds

Phosphorylated sugars are key intermediates in energy generation and biosyntheses

11.2 Monosaccharides Are Linked to Form Complex Carbohydrates

Sucrose, lactose, and maltose are the common disaccharides

Glycogen and starch are storage forms of glucose

Cellulose, a structural component of plants, is made of chains of glucose

Human milk oligosaccharides protect newborns from infection

11.3 Carbohydrates Can Be Linked to Proteins to Form Glycoproteins

Carbohydrates can be linked to proteins through asparagine (N-linked) or through serine or threonine (O-linked) residues

The glycoprotein erythropoietin is a vital hormone

Glycosylation functions in nutrient sensing

Proteoglycans, composed of polysaccharides and protein, have important structural roles

Proteoglycans are important components of cartilage

Mucins are glycoprotein components of mucus

Chitin can be processed to a molecule with a variety of uses

Protein glycosylation takes place in the lumen of the endoplasmic reticulum and in the Golgi complex

Specific enzymes are responsible for oligosaccharide assembly

Blood groups are based on protein glycosylation patterns

Errors in glycosylation can result in pathological conditions

Oligosaccharides can be “sequenced”

11.4 Lectins Are Specific Carbohydrate-Binding Proteins

Lectins promote interactions between cells and within cells

Lectins are organized into different classes

Influenza virus binds to sialic acid residues

APPENDIX Biochemistry in Focus: α-Glucosidase (maltase) inhibitors can help to maintain blood glucose homeostsis

Chapter 12 Lipids and Cell Membranes

12.1 Fatty Acids Are Key Constituents of Lipids

Fatty acid names are based on their parent hydrocarbons

Fatty acids vary in chain length and degree of unsaturation

12.2 There Are Three Common Types of Membrane Lipids

Phospholipids are the major class of membrane lipids

Membrane lipids can include carbohydrate moieties

Cholesterol is a lipid based on a steroid nucleus

Archaeal membranes are built from ether lipids with branched chains

A membrane lipid is an amphipathic molecule containing a hydrophilic and a hydrophobic moiety

12.3 Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous Media

Lipid vesicles can be formed from phospholipids

Lipid bilayers are highly impermeable to ions and most polar molecules

12.4 Proteins Carry Out Most Membrane Processes

Proteins associate with the lipid bilayer in a variety of ways

Proteins interact with membranes in a variety of ways

Some proteins associate with membranes through covalently attached hydrophobic groups

Transmembrane helices can be accurately predicted from amino acid sequences

12.5 Lipids and Many Membrane Proteins Diffuse Rapidly in the Plane of the Membrane

The fluid mosaic model allows lateral movement but not rotation through the membrane

Membrane fluidity is controlled by fatty acid composition and cholesterol content

Lipid rafts are highly dynamic complexes formed between cholesterol and specific lipids

All biological membranes are asymmetric

12.6 Eukaryotic Cells Contain Compartments Bounded by Internal Membranes

APPENDIX Biochemistry in Focus: The curious case of cardiolipin

Chapter 13 Membrane Channels and Pumps

13.1 The Transport of Molecules Across a Membrane May Be Active or Passive

Many molecules require protein transporters to cross membranes

Free energy stored in concentration gradients can be quantified

13.2 Two Families of Membrane Proteins Use ATP Hydrolysis to Pump Ions and Molecules Across Membranes

P-type ATPases couple phosphorylation and conformational changes to pump calcium ions across membranes

Digitalis specifically inhibits the Na+–K+ pump by blocking its dephosphorylation

P-type ATPases are evolutionarily conserved and play a wide range of roles

Multidrug resistance highlights a family of membrane pumps with ATP-binding cassette domains

13.3 Lactose Permease Is an Archetype of Secondary Transporters That Use One Concentration Gradient to Power the Formation of Another

13.4 Specific Channels Can Rapidly Transport Ions Across Membranes

Action potentials are mediated by transient changes in Na+ and K+ permeability

Patch-clamp conductance measurements reveal the activities of single channels

The structure of a potassium ion channel is an archetype for many ion-channel structures

The structure of the potassium ion channel reveals the basis of ion specificity

The structure of the potassium ion channel explains its rapid rate of transport

Voltage gating requires substantial conformational changes in specific ion-channel domains

A channel can be inactivated by occlusion of the pore: the ball-and-chain model

The acetylcholine receptor is an archetype for ligand-gated ion channels

Action potentials integrate the activities of several ion channels working in concert

Disruption of ion channels by mutations or chemicals can be potentially life-threatening

13.5 Gap Junctions Allow Ions and Small Molecules to Flow Between Communicating Cells

13.6 Specific Channels Increase the Permeability of Some Membranes to Water

APPENDIX Biochemistry in Focus: Setting the pace is more than funny business

APPENDIX Problem-Solving Strategies

Chapter 14 Signal-Transduction Pathways

14.1 Epinephrine and Angiotensin II Signaling: Heterotrimeric G Proteins Transmit Signals and Reset Themselves

Ligand binding to 7TM receptors leads to the activation of heterotrimeric G proteins

Activated G proteins transmit signals by binding to other proteins

Cyclic AMP stimulates the phosphorylation of many target proteins by activating protein kinase A

G proteins spontaneously reset themselves through GTP hydrolysis

Some 7TM receptors activate the phosphoinositide cascade

Calcium ion is a widely used second messenger

Calcium ion often activates the regulatory protein calmodulin

14.2 Insulin Signaling: Phosphorylation Cascades Are Central to Many Signal-Transduction Processes

The insulin receptor is a dimer that closes around a bound insulin molecule

Insulin binding results in the cross-phosphorylation and activation of the insulin receptor

The activated insulin-receptor kinase initiates a kinase cascade

Insulin signaling is terminated by the action of phosphatases

14.3 EGF Signaling: Signal-Transduction Pathways Are Poised to Respond

EGF binding results in the dimerization of the EGF receptor

The EGF receptor undergoes phosphorylation of its carboxyl-terminal tail

EGF signaling leads to the activation of Ras, a small G protein

Activated Ras initiates a protein kinase cascade

EGF signaling is terminated by protein phosphatases and the intrinsic GTPase activity of Ras

14.4 Many Elements Recur with Variation in Different Signal-Transduction Pathways

14.5 Defects in Signal-Transduction Pathways Can Lead to Cancer and Other Diseases

Monoclonal antibodies can be used to inhibit signal-transduction pathways activated in tumors

Protein kinase inhibitors can be effective anticancer drugs

Cholera and whooping cough are the result of altered G-protein activity

APPENDIX Biochemistry in Focus: Gases get in on the signaling game

Part II TRANSDUCING AND STORING ENERGY

Chapter 15 Metabolism: Basic Concepts and Design

15.1 Metabolism Is Composed of Many Coupled, Interconnecting Reactions

Metabolism consists of energy-yielding and energy-requiring reactions

A thermodynamically unfavorable reaction can be driven by a favorable reaction

15.2 ATP Is the Universal Currency of Free Energy in Biological Systems

ATP hydrolysis is exergonic

ATP hydrolysis drives metabolism by shifting the equilibrium of coupled reactions

The high phosphoryl potential of ATP results from structural differences between ATP and its hydrolysis products

Phosphoryl-transfer potential is an important form of cellular energy transformation

15.3 The Oxidation of Carbon Fuels Is an Important Source of Cellular Energy

Compounds with high phosphoryl-transfer potential can couple carbon oxidation to ATP synthesis

Ion gradients across membranes provide an important form of cellular energy that can be coupled to ATP synthesis

Phosphates play a prominent role in biochemical processes

Energy from foodstuffs is extracted in three stages

15.4 Metabolic Pathways Contain Many Recurring Motifs

Activated carriers exemplify the modular design and economy of metabolism

Many activated carriers are derived from vitamins

Key reactions are reiterated throughout metabolism

Metabolic processes are regulated in three principal ways

Aspects of metabolism may have evolved from an RNA world

APPENDIX Problem-Solving Strategies

Chapter 16 Glycolysis and Gluconeogenesis

16.1 Glycolysis Is an Energy-Conversion Pathway in Many Organisms

The enzymes of glycolysis are associated with one another

Glycolysis can be divided into two parts

Hexokinase traps glucose in the cell and begins glycolysis

Fructose 1,6-bisphosphate is generated from glucose 6-phosphate

The six-carbon sugar is cleaved into two three-carbon fragments

Mechanism: Triose phosphate isomerase salvages a three-carbon fragment

The oxidation of an aldehyde to an acid powers the formation of a compound with high phosphoryl-transfer potential

Mechanism: Phosphorylation is coupled to the oxidation of glyceraldehyde 3-phosphate by a thioester intermediate

ATP is formed by phosphoryl transfer from 1,3-bisphosphoglycerate

Additional ATP is generated with the formation of pyruvate

Two ATP molecules are formed in the conversion of glucose into pyruvate

NAD+ is regenerated from the metabolism of pyruvate

Fermentations provide usable energy in the absence of oxygen

Fructose is converted into glycolytic intermediates by fructokinase

Excessive fructose consumption can lead to pathological conditions

Galactose is converted into glucose 6-phosphate

Many adults are intolerant of milk because they are deficient in lactase

Galactose is highly toxic if the transferase is missing

16.2 The Glycolytic Pathway Is Tightly Controlled

Glycolysis in muscle is regulated to meet the need for ATP

The regulation of glycolysis in the liver illustrates the biochemical versatility of the liver

A family of transporters enables glucose to enter and leave animal cells

Aerobic glycolysis is a property of rapidly growing cells

Cancer and endurance training affect glycolysis in a similar fashion

16.3 Glucose Can Be Synthesized from Noncarbohydrate Precursors

Gluconeogenesis is not a reversal of glycolysis

The conversion of pyruvate into phosphoenolpyruvate begins with the formation of oxaloacetate

Oxaloacetate is shuttled into the cytoplasm and converted into phosphoenolpyruvate

The conversion of fructose 1,6-bisphosphate into fructose 6-phosphate and orthophosphate is an irreversible step

The generation of free glucose is an important control point

Six high-transfer-potential phosphoryl groups are spent in synthesizing glucose from pyruvate

16.4 Gluconeogenesis and Glycolysis Are Reciprocally Regulated

Energy charge determines whether glycolysis or gluconeogenesis will be most active

The balance between glycolysis and gluconeogenesis in the liver is sensitive to blood-glucose concentration

Substrate cycles amplify metabolic signals and produce heat

Lactate and alanine formed by contracting muscle are used by other organs

Glycolysis and gluconeogenesis are evolutionarily intertwined

APPENDIX Biochemistry in Focus: Triose phosphate isomerase deficiency (TPID)

APPENDIX Biochemistry in Focus: Pyruvate carboxylase deficiency (PCD)

APPENDIX Problem-Solving Strategies

Chapter 17 The Citric Acid Cycle

17.1 The Pyruvate Dehydrogenase Complex Links Glycolysis to the Citric Acid Cycle

Mechanism: The synthesis of acetyl coenzyme A from pyruvate requires three enzymes and five coenzymes

Flexible linkages allow lipoamide to move between different active sites

17.2 The Citric Acid Cycle Oxidizes Two-Carbon Units

Citrate synthase forms citrate from oxaloacetate and acetyl coenzyme A

Mechanism: The mechanism of citrate synthase prevents undesirable reactions

Citrate is isomerized into isocitrate

Isocitrate is oxidized and decarboxylated to alpha-ketoglutarate

Succinyl coenzyme A is formed by the oxidative