BIOCHEMISTRY - L. Stryer - 1984
VOLUME 1
BIOCHEMISTRY - L. Stryer - 1984 VOLUME 1
Translation Editor's Preface
Preface to the Second Edition
Preface to the First Edition
1.1. Molecular Models
1.3. Organization of This Book
PART I. CONFORMATION AND DYNAMICS
CHAPTER 2. INTRODUCTION TO PROTEIN STRUCTURE AND FUNCTION
2.1. Proteins Are Built from Amino Acids
2.2. Modified Amino Acids Supplement the Standard Set of Twenty Amino Acids
2.3. Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains
2.4. Proteins Consist of One or More Polypeptide Chains
2.5. Proteins Can Be Purified by a Variety of Methods
2.6. The Amino Acid Sequence of a Protein Is Unique and Genetically Determined
2.7. Experimental Methods for Determining Amino Acid Sequences
2.8. Conformation of Polypeptide Chains
2.9. Periodic Structures: Alpha Helix, Beta Pleated Sheet, and Collagen Helix
2.10. Polypeptide Chains Can Turn by 180° by Forming β-Turns
2.11. Levels of Structure in Protein Architecture
2.12. Amino Acid Sequence Determines Three-Dimensional Structure
2.13. Folding of Protein Molecules Occurs through the Association of α-Helices and β-Pleated Sheets
APPENDIX. CONCEPTS OF ACIDITY AND BASICITY
Ionization of water
Definition of acids and bases
Determination of pH and pK values
Henderson-Hasselbalch equation
Buffer capacity
pK values of amino acids
CHAPTER 3. OXYGEN CARRIERS—MYOGLOBIN AND HEMOGLOBIN
3.1. Oxygen binds to the heme prosthetic group
3.2. X-ray diffraction analysis of crystals reveals the spatial arrangement of atoms
3.3. Steps in the X-ray structure analysis of myoglobin
3.4. Myoglobin structure is characterized by compactness and a high degree of α-helical content
3.5. The oxygen-binding site in myoglobin
3.6. The rigid environment of the heme ensures the reversibility of oxygenation
3.7. The presence of distal histidine reduces carbon monoxide binding
3.8. Myoglobin has virtually the same structure in solution and in the crystalline state
3.9. Nonpolar interactions play an important role in stabilizing the conformation of myoglobin
3.10. The unfolded myoglobin molecule spontaneously adopts a functionally active conformation
3.11. Hemoglobin consists of four polypeptide chains
3.12. X-ray structure analysis of hemoglobin
3.13. Quaternary structure of hemoglobin
3.14. The α- and β-chains of hemoglobin are very similar to myoglobin
3.15. Critically essential residues in the amino acid sequence
3.16. The emergence of hemoglobin: a new stage in evolution
CHAPTER 4. HEMOGLOBIN: AN ALLOSTERIC PROTEIN
4.1. Functional differences between myoglobin and hemoglobin
4.2. Cooperativity of oxygen binding by hemoglobin
4.3. Cooperative oxygen binding by hemoglobin enhances oxygen transport
4.4. H+ and CO2 promote the release of O2 (the Bohr effect)
4.5. Bisphosphoglycerate reduces oxygen affinity
4.6. Clinical significance of bisphosphoglycerate
4.7. Fetal hemoglobin has a high affinity for oxygen
4.8. Allosteric effects require subunit interaction
4.9. The quaternary structure of hemoglobin changes significantly upon oxygenation
4.10. Salt bridges between individual chains impart rigidity to the structure of deoxyhemoglobin
4.11. Upon oxygenation, the iron atom moves into the plane of the porphyrin
4.12. The movement of the iron atom is transmitted to other subunits via the proximal histidine
4.13. Mechanism of cooperative oxygen binding
4.14. Bisphosphoglycerate reduces oxygen affinity by cross-linking with deoxyhemoglobin
4.15. CO2 binds to the terminal amino groups of hemoglobin, reducing its oxygen affinity
4.16. Mechanism of the Bohr effect
4.17. Communication within the protein molecule
CHAPTER 5. MOLECULAR DISEASES: SICKLE-CELL ANEMIA
5.1. Sickle-cell anemia is an inherited chronic hemolytic disease
5.2. Deoxygenated sickle-cell hemoglobin has reduced solubility
5.3. Hemoglobin S differs from hemoglobin A in electrophoretic mobility
5.4. Peptide mapping: identifying the amino acid substitution in sickle-cell hemoglobin
5.5. A single amino acid is substituted in the β-chain
5.6. Sickle-cell hemoglobin has "sticky" patches on its surface
5.7. Deoxyhemoglobin S forms long, helical fibers
5.8. The rate of fiber formation is highly dependent on the concentration of deoxyhemoglobin S
5.9. The high frequency of the sickle-cell gene is due to its protective effect against malaria
5.10. Drug discovery strategies for the treatment of sickle-cell anemia
5.11. Molecular pathology of hemoglobin
5.12. Hemoglobin M: a product of mutation in the active site
5.13. Polar groups in the heme pocket weaken its binding to the polypeptide chain
5.14. Certain mutations destabilize hemoglobins by distorting their tertiary structure
5.15. Mutations at contact interfaces disrupt allosteric interactions
5.16. Significance of the discovery of mutant hemoglobins
CHAPTER 6. INTRODUCTION TO ENZYMES
6.1. Enzymes have enormous catalytic power
6.2. Enzymes are highly specific
6.3. The activity of some enzymes is regulated
6.4. Enzymes transform different forms of energy
6.5. Enzymes do not alter reaction equilibria
6.6. Enzymes decrease the activation energy of the reactions they catalyze
6.7. The first step in enzymatic catalysis is the formation of an enzyme-substrate complex
6.8. Some properties of active sites
6.9. The kinetics of many enzymes follow the Michaelis-Menten model
6.10. Vmax and Km can be determined using different substrate concentrations
6.11. Significance of Km and Vmax values
6.12. The kinetic perfection of enzyme catalysis is evaluated by the kcat/Km ratio
6.13. Enzymes can be inhibited by specific molecules
6.14. Competitive and noncompetitive inhibition differ in their kinetics
6.15. Treatment of ethylene glycol poisoning based on competitive inhibition
6.16. Allosteric enzymes do not obey Michaelis-Menten kinetics
6.17. The concerted mechanism of allosteric interactions
6.18. The sequential mechanism of allosteric interactions
6.19. Hydrogen bonds, electrostatic, and van der Waals interactions in enzyme-substrate complexes
6.20. Charged substrates can bind to oppositely charged groups on the enzyme
6.21. Highly directional hydrogen bonds are formed upon substrate binding to enzymes
6.22. Proteins have a pronounced ability to form hydrogen bonds
6.23. Van der Waals interactions play an important role in cases of steric complementarity
6.24. Biologically important properties of water: water polarity and its cohesive properties
6.25. The presence of water weakens polar interactions
6.26. Hydrophobic interactions: nonpolar groups tend to associate in an aqueous environment
CHAPTER 7. MECHANISM OF ENZYME ACTION: LYSOZYME AND CARBOXYPEPTIDASE
7.1. Lysozyme cleaves bacterial cell walls
7.2. Three-dimensional structure of lysozyme
7.3. Identification of the active site of lysozyme
7.4. The mode of binding of a competitive inhibitor
7.5. From enzyme structure to the mechanism of enzyme action
7.6. Transient formation of a carbonium ion is a critical step in catalysis
7.7. Experimental evidence for the proposed mechanism of enzymatic catalysis
7.8. Carboxypeptidase A: a zinc-containing proteolytic enzyme
7.9. Substrate binding induces large structural changes in the active site of carboxypeptidase A
7.10. The rate of catalysis by carboxypeptidase A is enhanced by electronic strain
CHAPTER 8. ZYMOGEN ACTIVATION: DIGESTIVE ENZYMES AND BLOOD COAGULATION FACTORS
8.1. Chymotrypsinogen is activated by the specific cleavage of a single peptide bond
8.2. The three-dimensional structure of chymotrypsin
8.3. Chymotrypsin is specific for aromatic and bulky nonpolar side chains
8.4. In chymotrypsin catalysis, a portion of the substrate becomes covalently bound to the enzyme
8.5. The acyl group is linked to an unusually reactive serine residue on the enzyme
8.6. The involvement of histidine-57 in catalysis is revealed by affinity labeling
8.7. A charge-relay system serves as a proton shuttle in catalysis
8.8. Chymotrypsin contains a deep pocket for binding the aromatic side chain
8.9. A transient tetrahedral intermediate is formed during catalysis
8.10. The mechanism of zymogen activation
8.11. Trypsin and elastase: variations on a theme
8.12. Pancreatic trypsin inhibitor binds tightly to the active site of trypsin
8.13. Divergent and convergent evolution of serine proteases
8.14. Coordinated activation of pancreatic zymogens
8.15. Premature activation of zymogens can be fatal, as in pancreatitis
8.16. The major types of proteolytic enzymes are serine proteases and carboxyproteases
8.17. Blood clotting as a cascade of zymogen activation reactions
8.18. Blood clot formation requires the interaction of two types of enzymatic transformations
8.19. Fibrinogen is converted into a fibrin clot by thrombin
8.20. Fibrin monomers spontaneously form fibrils
8.21. The fibrin clot is stabilized by covalent cross-links
8.22. Thrombin is homologous to trypsin
8.23. Vitamin K is required for prothrombin synthesis
8.24. Prothrombin is activated by factor X on the phospholipid surface of platelets
8.25. Hemophilia and other bleeding disorders have helped elucidate several early steps in blood clot formation
8.26. The intrinsic pathway of blood clotting
8.27. The extrinsic pathway of blood clotting
8.28. Regulation of blood clotting: a problem requiring attention
CHAPTER 9. CONNECTIVE TISSUE PROTEINS: COLLAGEN, ELASTIN, AND PROTEOGLYCANS
9.1. Tropocollagen as the basic structural unit of collagen
9.2. Collagen has an unusual amino acid composition and sequence
9.3. Some proline and lysine residues in collagen are hydroxylated
9.4. Sugars are attached to hydroxylysine residues
9.5. The structure of tropocollagen is a triple helix
9.6. The small size of glycine makes it an indispensable structural component
9.7. The stability of the collagen helix depends on cooperative interactions
9.8. Impaired hydroxylation is a biochemical defect in scurvy
9.9. Procollagen is the precursor of collagen in its biosynthesis
9.10. Extension peptides of precursor chains are cleaved enzymatically
9.11. Collagen fibers consist of staggered tropocollagen molecules
9.12. Collagen fiber formation is regulated by procollagen peptidases
9.13. Cross-links increase the strength of collagen fibers
9.14. Collagenases are enzymes that specifically cleave collagen
9.15. Elastin is a rubber-like protein of elastic fibers
9.16. Proteoglycans form the ground substance of connective tissue
CHAPTER 10. INTRODUCTION TO BIOLOGICAL MEMBRANES
10.1. Common features of biological membranes
10.2. Phospholipids are the major class of membrane lipids
10.3. Most membranes also contain glycolipids and cholesterol
10.4. Phospholipids and glycolipids readily form bilayers
10.5. Lipid bilayers are noncovalent cooperative structures
10.6. Lipid bilayers are impermeable to ions and many polar molecules
10.7. Most membrane processes are mediated by proteins
10.8. Reconstitution of functioning membrane systems from purified components
10.9. Some membrane proteins are deeply embedded in the lipid bilayer
10.10. The erythrocyte membrane contains various peripheral and integral proteins
10.11. The erythrocyte membrane is spanned by an anion channel and glycophorin, a complex protein
10.12. Carbohydrate units are located on the outer surface of the plasma membrane
10.13. Lipids and many membrane proteins diffuse rapidly in the plane of the membrane
10.14. Membrane proteins do not flip-flop across bilayers
10.15. The fluid mosaic model of biological membranes
10.16. Membranes are asymmetric
10.17. Membrane fluidity depends on fatty acid composition and cholesterol content
10.18. Three-dimensional membrane model based on electron microscopy data