內容簡介
Enzyme catalysis is a topic of fundamental importance in organic, bio-organic and medicinal chemistry. This new edition of a very popular textbook provides a concise introduction to the underlying principles and mechanisms of enzyme and coenzyme action from a chemical perspective.
Whilst retaining the overall structure of the first edition – preliminary chapters describe the basic principles of enzyme structure and catalysis moving through to detailed discussions of the major classes of enzyme processes in the later chapters – the book has been thoroughly updated to include information on the most recent advances in our understanding of enzyme action. A major feature of the second edition is the inclusion of two-colour figures of the active sites of enzymes discussed in the text, in order to illustrate the interplay between enzyme structure and function. Problems, with outline answers, at the end of each chapter give the student the chance to the check their understanding of the material.
As a concise but comprehensive account, Introduction to Enzyme and Coenzyme Chemistry will continue to prove invaluable to both undergraduate and postgraduate students of organic, bio-organic and medicinal chemistry.
作者簡介
Tim Bugg is professor of biological chemistry in the Department of Chemistry, University of Warwick, UK.
目次
1. From Jack Beans to Designer Genes
1.1 Introduction
1.2 The discovery of enzymes
1.3 The discovery of coenzymes
1.4 The commercial importance of enzymes in biosynthesis and biotechnology
1.5 The importance of enzymes as targets for drug discovery
2. All Enzymes are Proteins
2.1 Introduction
2.2 The structures of the l-a-amino acids
2.3 The primary structure of polypeptides
2.4 Alignment of amino acid sequences
2.5 Secondary structures found in proteins
2.6 The folded tertiary structure of proteins
2.7 Enzyme structure and function
2.8 Metallo-enzymes
2.9 Membrane-associated enzymes
2.10 Glycoproteins
3. Enzymes are Wonderful Catalysts
3.1 Introduction
3.2 A thermodynamic model of catalysis
3.3 Proximity eVects
3.4 The importance of transition state stabilisation
3.5 Acid/base catalysis in enzymatic reactions
3.6 Nucleophilic catalysis in enzymatic reactions
3.7 The use of strain energy in enzyme catalysis
3.8 Catalytic perfection
3.9 The involvement of protein dynamics in enzyme catalysis
4. Methods for Studying Enzymatic Reactions
4.1 Introduction
4.2 Enzyme puriWcation
4.3 Enzyme kinetics
4.4 The stereochemical course of an enzymatic reaction
4.5 The existence of intermediates in enzymatic reactions
4.6 Analysis of transition states in enzymatic reactions
4.7 Determination of active site catalytic groups
5. Enzymatic Hydrolysis and Group Transfer Reactions
5.1 Introduction
5.2 The peptidases
CASE STUDY: HIV-1 protease
5.3 Esterases and lipases
5.4 Acyl transfer reactions in biosynthesis: use of coenzyme A (CoA)
5.5 Enzymatic phosphoryl transfer reactions
5.6 Adenosine 50-triphosphate
5.7 Enzymatic glycosyl transfer reactions
5.8 Methyl group transfer: use of S-adenosyl methionine and tetrahydrofolate coenzymes for one-carbo
6. Enzymatic Redox Chemistry
6.1 Introduction
6.2 Nicotinamide adenine dinucleotide-dependent dehydrogenases
6.3 Flavin-dependent dehydrogenases and oxidases
6.4 Flavin-dependent mono-oxygenases
6.5 CASE STUDY: Glutathione and trypanothione reductases
6.6 DeazaXavins and pterins
6.7 Iron–sulphur clusters
6.8 Metal-dependent mono-oxygenases
6.9 a-Ketoglutarate-dependent dioxygenases
6.10 Non-haem iron-dependent dioxygenases
7. Enzymatic Carbon–Carbon Bond Formation
7.1 Introduction
Carbon–carbon bond formation via carbanion equivalents
7.2 Aldolases
CASE STUDY: Fructose-1,6-bisphosphate aldolase
7.3 Claisen enzymes
7.4 Assembly of fatty acids and polyketides
7.5 Carboxylases: use of biotin
7.6 Ribulose bisphosphate carboxylase/oxygenase (Rubisco)
7.7 Vitamin K-dependent carboxylase
7.8 Thiamine pyrophosphate-dependent enzymes
Carbon–carbon bond formation via carbocation intermediates
7.9 Terpene cyclases
Carbon–carbon bond formation via radical intermediates
7.10 Phenolic radical couplings
8. Enzymatic Addition/Elimination Reactions
8.1 Introduction
8.2 Hydratases and dehydratases
8.3 Ammonia lyases
8.4 Elimination of phosphate and pyrophosphate
8.5 CASE STUDY: 5-Enolpyruvyl-shikimate-3-phosphate (EPSP) synthase
9. Enzymatic Transformations of Amino Acids
9.1 Introduction
9.2 Pyridoxal 50-phosphate-dependent reactions at the a-position of amino acids
9.3 CASE STUDY: Aspartate aminotransferase
9.4 Reactions at b- and g-positions of amino acids
9.5 Serine hydroxymethyltransferase
9.6 N-Pyruvoyl-dependent amino acid decarboxylases
9.7 Imines and enamines in alkaloid biosynthesis
10. Isomerases
10.1 Introduction
10.2 Cofactor-independent racemases and epimerases
10.3 Keto–enol tautomerases
10.4 Allylic isomerases
10.5 CASE STUDY: Chorismate mutase
11. Radicals in Enzyme Catalysis
11.1 Introduction
11.2 Vitamin B12-dependent rearrangements
11.3 The involvement of protein radicals in enzyme catalysis
11.4 S-adenosyl methionine-dependent radical reactions
11.5 Biotin synthase and sulphur insertion reactions
11.6 Oxidised amino acid cofactors and quinoproteins
12. Non-Enzymatic Biological Catalysis
12.1 Introduction
12.2 Catalytic RNA
12.3 Catalytic antibodies
12.4 Synthetic enzyme models
Appendices
1. Cahn–Ingold–Prelog rule for stereochemical nomenclature
2. Amino acid abbreviations
3. A simple demonstration of enzyme catalysis
4. Answers to problems
Index
