The Organic Chemistry of Enzyme-Catalyzed Reactions / Edition 1

The Organic Chemistry of Enzyme-Catalyzed Reactions / Edition 1

by Richard B. Silverman
     
 

ISBN-10: 0126437459

ISBN-13: 9780126437454

Pub. Date: 12/28/1999

Publisher: Elsevier Science & Technology Books

This unique text illuminates the "black box" of enzyme-catalyzed reactions by showing how enzymes are simply highly efficient organic chemists. Illustrated with a vast number of computer-drawn structures and reaction schemes, each chapter describes the organic reaction mechanisms that enzymes use to catalyze a particular family of organic transformations. Rather than

Overview

This unique text illuminates the "black box" of enzyme-catalyzed reactions by showing how enzymes are simply highly efficient organic chemists. Illustrated with a vast number of computer-drawn structures and reaction schemes, each chapter describes the organic reaction mechanisms that enzymes use to catalyze a particular family of organic transformations. Rather than bogging the reader down with all of the enzymes that catalyze a transformation, Professor Silverman selects one or two examples of enzymes that catalyze the particular chemistry. Chemical model studies used to elucidate enzyme mechanisms are discussed, along with the design of haptens, the generation of catalytic antibodies ("designer enzymes"), and the design and mechanism of enzyme inhibitors. An extensive bibliography annotates the coverage of numerous experiments that aid in elucidating of the enzyme mechanisms. Problem sets and solutions are provided for each chapter. Intended as a textbook for courses in enzymology and bioorganic and medicinal chemistry, The Organic Chemistry of Enzyme-Catalyzed Reactions will also serve as an essential reference for chemists and biochemists working with enzymes in the chemical, pharmaceutical, agricultural, and biotechnology industries.

KEY FEATURES

· Shows how enzyme-catalyzed reactions are simply efficient organic reactions
· Emphasizes the connection between organic reaction mechanisms and enzyme mechanisms
· Explains how enzymes can accelerate the rates of chemical reactions with high specificity
· Uses selected enzymes to demonstrate general mechanisms of enzyme-catalyzed reactions
· Compiles the latest information about molecular mechanisms of enzyme reactions
· Illustrated with a vast array of clearly drawn structures, schemes, and figures
· Includes an extensive bibliography on enzyme mechanisms
· Describes approaches to the design of enzyme inhibitors
· Covers catalytic antibody design and mechanisms
· Provides problem sets and solutions for each chapter
· Written in an informal and engaging style

Product Details

ISBN-13:
9780126437454
Publisher:
Elsevier Science & Technology Books
Publication date:
12/28/1999
Edition description:
New Edition
Pages:
718
Product dimensions:
6.39(w) x 9.35(h) x 1.44(d)

Table of Contents

Prefacexiii
About the Authorxvii
1Enzymes as Catalysts
I.What Are Enzymes, and How Do They Work?1
A.Historical1
B.Specificity of Enzyme-Catalyzed Reactions4
C.Rate Acceleration13
II.Mechanisms of Enzyme Catalysis15
A.Approximation16
B.Covalent Catalysis18
C.General Acid/Base Catalysis20
D.Electrostatic Catalysis28
E.Desolvation30
F.Strain or Distortion30
III.Enzyme Catalysis in Organic Media33
IV.Enzyme Nomenclature34
V.Epilogue35
References36
2Group Transfer Reactions: Hydrolysis, Amination, Phosphorylation
I.Hydrolysis Reactions39
A.Amide Hydrolysis: Peptidases39
B.Ester Hydrolysis: Esterases and Lipases60
II.Aminations64
A.Glutamine-Dependent Enzymes64
B.Aspartic Acid as a Source of Ammonia76
III.Phosphorylations: Transfers of Phosphate and Phosphate Esters to Water or Other Acceptors76
A.Phosphatases79
B.Phosphodiesterases85
C.Kinases87
References90
3Reduction and Oxidation
I.General95
II.Redox without a Coenzyme95
III.Redox Reactions That Require Coenzymes100
A.Nicotinamide Coenzymes (Pyridine Nucleotides)100
B.Flavin Coenzymes119
C.Quinone-Containing Coenzymes147
D.Other Redox Enzymes157
References169
4Monooxygenation
I.General175
II.Flavin-Dependent Hydroxylases175
A.No Reducing Agent Required175
B.Hydroxylases Requiring an External Reducing Agent177
III.Pterin-Dependent Hydroxylases188
A.General188
B.Mechanism189
IV.Heme-Dependent Monooxygenases193
A.General193
B.Molecular Oxygen Activation196
C.Mechanistic Considerations198
V.Nonheme Iron Oxygenation218
A.Methane Monooxygenase218
VI.Copper-Dependent Oxygenation219
A.Dopamine [beta]-Monooxygenase219
References223
5Dioxygenation
I.General227
II.Intramolecular Dioxygenases227
A.Catechol Dioxygenases227
B.Prostaglandin H Synthase (Cyclooxygenase)232
III.Intermolecular Dioxygenases239
A.[alpha]-Keto Acid-Dependent Dioxygenases239
References248
6Substitutions
I.S[subscript N]1251
A.Farnesyl Diphosphate Synthase and Related Enzymes251
II.S[subscript N]1/S[subscript N]2257
A.Disaccharide Phosphorylases257
B.[beta]-Glycosidases260
III.S[subscript N]2262
IV.S[subscript N]2'265
V.S[subscript N]Ar: Nucleophilic Aromatic Substitution268
VI.Electrophilic Substitution (Addition/Elimination)273
VII.Electrophilic Aromatic Substitution282
References286
7Carboxylations
I.General Concepts289
II.Carbon Dioxide as the Carboxylating Agent290
A.Phosphoenolpyruvate (PEP) Carboxykinase290
B.Phosphoenolpyruvate Carboxytransphosphorylase293
C.Vitamin K-Dependent Carboxylation of Proteins297
III.Bicarbonate as the Carboxylating Agent303
A.Phosphoenolpyruvate Carboxylase303
B.Biotin-Dependent Carboxylases307
References319
8Decarboxylation
I.General321
II.[beta]-Keto Acids321
A.Schiff Base Mechanism323
B.Metal Ion-Catalyzed Mechanism327
III.[beta]-Hydroxy Acids329
A.Isocitrate Dehydrogenase329
B.6-Phosphogluconate Dehydrogenase330
IV.[alpha]-Keto Acids331
A.General331
B.Chemistry and Properties of Thiamin Diphosphate331
C.Mechanism of Thiamin Diphosphate-Dependent Enzymes335
V.Amino Acids343
A.Pyridoxal Phosphate-Dependent Decarboxylation343
B.Pyruvoyl-Dependent Decarboxylation348
VI.Other Substrates349
A.Orotidine 5'-Monophosphate349
B.Mevalonate Diphosphate354
References356
9Isomerizations
I.General359
II.[1,1]-Hydrogen Shift359
A.Amino Acid Racemases That Require No Cofactors359
B.Amino Acid Racemases That Require Pyridoxal 5'-Phosphate364
C.Other Racemases367
D.Epimerases369
III.[1,2]-Hydrogen Shift376
A.Aldose-Ketose Isomerases376
IV.[1,3]-Hydrogen Shift378
A.Enolization378
B.Allylic Isomerizations379
C.Aza-Allylic Isomerizations387
V.Cis/Trans Isomerizations390
A.Maleylacetoacetate Isomerase390
B.Retinol Isomerase391
C.Catalytic Antibody-Catalyzed Cis/Trans Isomerization393
VI.Phosphate Isomerization393
References395
10Eliminations and Additions
I.Anti Eliminations and Additions399
A.Dehydratases and Hydratases399
B.Elimination of Phosphate420
C.Ammonia Lyases: Elimination of Ammonia424
II.Syn Eliminations and Additions428
A.Schiff Base Mechanism429
B.Pyridoxal 5'-Phosphate-Dependent Eliminations430
C.Pyridoxamine 5'-Phosphate and Iron-Sulfur Cluster-Dependent Reactions445
D.A Catalytic Antibody-Catalyzed Syn Elimination448
References449
11Aldol and Claisen Reactions and Retroreactions
I.Aldol Reactions453
A.General Chemical Considerations453
B.Aldolases454
C.Porphobilinogen Synthase (5-Aminolevulinate Dehydratase)458
D.ATP Citrate-Lyase464
E.Transketolase467
F.Dehydroquinate Synthase468
II.Claisen Reactions471
A.General471
B.Thiolase472
C.Kynureninase474
References476
12Formylations, Hydroxymethylations, and Methylations
I.Tetrahydrofolate-Dependent Enzymes: The Transfer of One-Carbon Units479
A.Formation of the Active Coenzyme479
B.Transfer of One-Carbon Units483
II.S-Adenosylmethionine-Dependent Enzymes: The Transfer of Methyl Groups500
References502
13Rearrangements
I.Pericyclic Reactions505
A.Sigmatropic Rearrangements505
B.Cycloaddition Reactions511
II.Rearrangements That Proceed via Carbenium Ion Intermediates516
A.Acyloin Rearrangement516
B.Cyclizations518
III.Rearrangements That Proceed via Radical Intermediates526
A.DNA Photolyase, Formally a [2+2] Cycloreversion Reaction526
B.Coenzyme B[subscript 12]-Dependent and Related Rearrangements530
IV.Epilogue554
References556
Appendix IEnzyme Kinetics563
I.Substrate Kinetics563
A.Michaelis-Menten Equation563
B.Graphical Representations567
II.Kinetics of Enzyme Inhibition570
A.Reversible Enzyme Inhibition570
B.Irreversible Enzyme Inhibition584
III.Substrate Inhibition587
IV.Nonproductive Binding589
V.Competing Substrates590
VI.Multisubstrate Systems591
A.Sequential Mechanisms591
VII.Allosterism and Cooperativity593
A.General593
B.Monod-Wyman-Changeux (MWC) Concerted Model594
C.Koshland-Nemethy-Filmer (KNF) Sequential Model595
General References596
References596
Appendix IIProblems and Solutions597
I.Problems597
A.Chapter 1597
B.Chapter 2600
C.Chapter 3604
D.Chapter 4605
E.Chapter 5608
F.Chapter 6611
G.Chapter 7613
H.Chapter 8614
I.Chapter 9616
J.Chapter 10617
K.Chapter 11620
L.Chapter 12622
M.Chapter 13623
N.Biosynthetic Pathways624
II.Solutions to Problems626
A.Chapter 1626
B.Chapter 2631
C.Chapter 3636
D.Chapter 4643
E.Chapter 5650
F.Chapter 6655
G.Chapter 7657
H.Chapter 8662
I.Chapter 9667
J.Chapter 10672
K.Chapter 11681
L.Chapter 12686
M.Chapter 13688
N.Biosynthetic Pathways691
Index697

Customer Reviews

Average Review:

Write a Review

and post it to your social network

     

Most Helpful Customer Reviews

See all customer reviews >