Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

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From Jack Beans to Designer Genes 3 be used to catalyse new types of chemical reactions, or via gene therapy used to correct genetic defects in cellular enzymes which would otherwise lead to human diseases. 1.3 The discovery of coenzymes At the same time as the discovery of enzymes in the late 19th and early 20th centuries, a class of biologically important small molecules was being discovered which had remarkable properties to cure certain dietary disorders. These molecules were christened the vitamins, a corruption of the phrase ‘vital amines’ used to describe their dietary importance (several of the Wrst-discovered vitamins were amines, but this is not true of all the vitamins). The vitamins were later found to have very important cellular roles, shown in Table 1.1. The Wrst demonstration of the importance of vitamins in the human diet took place in 1753. A Scottish naval physician, James Lind, found that the disease scurvy, prevalent amongst mariners at that time, could be avoided by deliberately including green vegetables or citrus fruits in the sailors’ diets. This discovery was used by Captain James Cook to maintain the good health of his crew during his voyages of exploration in 1768–76. The active ingredient was elucidated much later as vitamin C, ascorbic acid. The Wrst vitamin to be identiWed as a chemical substance was thiamine, lack of which causes the limb paralysis beriberi. This nutritional deWciency was Wrst identiWed in the Japanese Navy in the late 19th century. The incidence of beriberi in sailors was connected with their diet of polished rice by Admiral Takaki, who eliminated the ailment in 1885 by improvement of the sailors’ diet. Subsequent investigations by Eijkman identiWed a substance present in rice husks able to cure beriberi. This vitamin was subsequently shown to be an essential ‘cofactor’ in cellular decarboxylation reactions, as we shall see in Chapter 7. Over a number of years the family of vitamins shown in Table 1.1 was identiWed and their chemical structures elucidated. Some, like vitamin C, have simple structures, whilst others, like vitamin B 12 , have very complex structures. It has taken much longer to elucidate the molecular details of their biochemical mode of action. Many of the vitamins are in fact coenzymes: small organic cofactors which are used by certain types of enzyme in order to carry out particular classes of reaction. Table 1.1 gives a list of the coenzymes that we are going to encounter in this book. 1.4 The commercial importance of enzymes in biosynthesis and biotechnology Many plants and micro-organisms contain natural products that possess potent biological activities. The isolation of these natural products has led to the
4 Chapter 1 Table 1.1 The vitamins. Vitamin Chemical name DeWciency disease Biochemical function Coenzyme chemistry A Retinol Night blindness Visual pigments — B 1 Thiamine Beriberi Coenzyme (TPP) Decarboxylation of a-keto acids B 2 RiboXavin Skin lesions Coenzyme (FAD, FMN) 1e =2e redox chemistry Niacin Nicotinamide Pellagra Coenzyme (NAD) Redox chemistry B 6 Pyridoxal Convulsions Coenzyme (PLP) Reactions of a-amino acids B 12 Cobalamine Pernicious anaemia Coenzyme Radical re-arrangements C Ascorbic acid Scurvy Coenzyme, anti-oxidant Redox agent (collagen formation) D Calciferols Rickets Calcium homeostasis — E Tocopherols Newborn haemolytic anaemia Anti-oxidant — H Biotin Skin lesions Coenzyme Carboxylation K Phylloquinone Bleeding disorders Coenzyme, anti-oxidant Carboxylation of glutamyl peptides Folic acid Megaloblastic anaemia Coenzyme (tetrahydrofolate) Pantothenic acid Burning foot syndrome Coenzyme (CoA, phosphopantotheine) 1-carbon transfers Acyl transfer CoA, coenzyme A; FAD, Xavin adenine dinucleotide; FMN, Xavin mononucleotide; NAD, nicotinamide adenine dinucleotide; PLP, pyridoxal-5 0 -phosphate; TPP, thiamine pyrophosphate. discovery of many biologically active compounds such as quinine, morphine and penicillin (Figure 1.2) which have been fundamental to the development of modern medicine. MeO HO H N N HO HO O H H NMe Ph O H N O H H N S CO 2 H quinine morphine Figure 1.2 Structures of quinine, morphine and penicillin G. penicillin G
Page 1 and 2: Introduction to Enzyme and Coenzyme
Page 4 and 5: Introduction to Enzyme and Coenzyme
Page 6 and 7: Contents Preface Representation of
Page 8: Contents vii 8 Enzymatic Addition/E
Page 11 and 12: Representation of Protein Three-Dim
Page 13: 2 Chapter 1 H 2 N O NH 2 + H 2 O Ja
Page 17 and 18: 6 Chapter 1 has very diVerent biolo
Page 19 and 20: 2 All Enzymes are Proteins 2.1 Intr
Page 21 and 22: 10 Chapter 2 (Gln). There are three
Page 23 and 24: 12 Chapter 2 AAA Lys ACA Thr AGA Ar
Page 25 and 26: 14 Chapter 2 H N O H N O Figure 2.8
Page 27 and 28: 16 Chapter 2 (a) (b) Figure 2.12 St
Page 29 and 30: 18 Chapter 2 Figure 2.14 Structure
Page 31 and 32: 20 Chapter 2 (a) X Y Enzyme + Subst
Page 33 and 34: 22 Chapter 2 maintaining protein te
Page 35 and 36: 24 Chapter 2 surface glycoprotein g
Page 37 and 38: 26 Chapter 2 O-linked glycosylation
Page 39 and 40: 28 Chapter 2 Metalloproteins I. Ber
Page 41 and 42: 30 Chapter 3 O N H R CO 2 H acylase
Page 43 and 44: 32 Chapter 3 (a) Free energy uncata
Page 45 and 46: 34 Chapter 3 Ester k rel Effective
Page 47 and 48: 36 Chapter 3 3.4 The importance of
Page 49 and 50: 38 Chapter 3 pKa Tyrosine CH 2 O H
Page 51 and 52: 40 Chapter 3 glycoside hydrolysis (
Page 53 and 54: 42 Chapter 3 O O Glu 143 O − R H
Page 55 and 56: 44 Chapter 3 the hydroxyl groups of
Page 57 and 58: 46 Chapter 3 E + S E + S ES' ES ‘
Page 59 and 60: 48 Chapter 3 Examination of protein
Page 61 and 62: 50 Chapter 3 (Note: Similar results
Page 63 and 64: 52 Chapter 4 (1) Direct UV (2) Radi
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54 Chapter 4 Figure 4.3 PuriWcation
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56 Chapter 4 The two kinetic consta
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58 Chapter 4 Lineweaver−Burk Plot
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60 Chapter 4 E + S K i EI+ I ES E +
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62 Chapter 4 (2) by treatment with
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64 Chapter 4 In general the stereoc
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H D T CO 2 H CO − 2 T HO D H −
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68 Chapter 4 4.5 The existence of i
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70 Chapter 4 18O 18O 18 O O P O −
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72 Chapter 4 If a reaction involves
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74 Chapter 4 O D H ketosteroid isom
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76 Chapter 4 Table 4.3 Group speciW
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78 Chapter 4 [S] (mM) Rate of produ
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80 Chapter 4 Enzyme kinetics I.H. S
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82 Chapter 5 O = C NHR peptidase H
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84 Chapter 5 non-speciWc protease c
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86 Chapter 5 His 57 His 57 Asp 102
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88 Chapter 5 Other serine proteases
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90 Chapter 5 Figure 5.8 Structure o
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92 Chapter 5 now predominate Perhap
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OH R O Zn 2+ O O O Ph Glu 270 H 2 N
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96 Chapter 5 CASE STUDY: HIV-1 prot
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98 Chapter 5 HO Transition state pe
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100 Chapter 5 The aminoacyl group o
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102 Chapter 5 5.5 Enzymatic phospho
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104 Chapter 5 Figure 5.29 Structure
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Page 119 and 120:
108 Chapter 5 Adenosine 5 0 -tripho
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110 Chapter 5 functional group. Gly
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112 Chapter 5 CH 2 OH O RO HO OH O
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114 Chapter 5 to these atoms that t
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116 Chapter 5 Problems (1) Using pa
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118 Chapter 5 (6) Retaining glycosi
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120 Chapter 5 J.R. Knowles (1980) E
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122 Chapter 6 +1.0 Redox potential
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Table 6.1 Classes of redox enzymes.
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126 Chapter 6 An important point is
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128 Chapter 6 O H − OH − O OH H
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130 Chapter 6 one-electron transfer
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132 Chapter 6 (a) R N H + N O R N H
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134 Chapter 6 Inactivation by trany
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Page 149 and 150:
138 Chapter 6 (a) (b) Figure 6.23 S
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140 Chapter 6 glutathione called tr
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142 Chapter 6 neither has a stable
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144 Chapter 6 of the haem cofactor
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146 Chapter 6 Figure 6.33 Active si
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148 Chapter 6 HO H N N O O H N prol
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150 Chapter 6 R R R O 2 , Fe 2+ O O
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152 Chapter 6 CoA. Explain these re
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154 Chapter 6 NADH models O. Almars
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7 Enzymatic Carbon-Carbon Bond Form
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158 Chapter 7 O H − OH O − O H
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162 Chapter 7 Figure 7.6 Active sit
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164 Chapter 7 7.3 Claisen enzymes I
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166 Chapter 7 CoAS O EnzB − H D T
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168 Chapter 7 onto the acetyl-thioe
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170 Chapter 7 In the case of erythr
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172 Chapter 7 O HO O − O ATP ADP
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174 Chapter 7 CO 2 − vitamin K-de
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176 Chapter 7 7.8 Thiamine pyrophos
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178 Chapter 7 HN N + N H NH S O OPP
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180 Chapter 7 O OH OH camphor geran
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182 Chapter 7 CH 3 * OPP (−)pinen
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186 Chapter 7 C C C C C O OCH 3 C H
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188 Chapter 7 AcO HO HO NHAc O OH +
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190 Chapter 7 (9) Usnic acid is a n
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192 Chapter 7 Radical couplings W.M
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194 Chapter 8 C-O cleavage H E1 H C
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196 Chapter 8 leads to the formatio
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198 Chapter 8 aconitase citrate cis
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200 Chapter 8 *H R H H CO 2 − NH
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202 Chapter 8 EnzB − 2 H − O 2
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204 Chapter 8 involves no change in
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206 Chapter 8 Glyphosate H H N CO
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208 Chapter 8 (5) Chorismic acid (s
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9 Enzymatic Transformations of Amin
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CO − − 2 CO 2 H H CO 2 − N +
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214 Chapter 9 - BEnz CO − 2 Cl H
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216 Chapter 9 Arg 292 Arg 292 Lys 2
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218 Chapter 9 Arg 292 Asp 292 HN H
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220 Chapter 9 S − B 1 Enz H − C
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222 Chapter 9 9.6 N-Pyruvoyl-depend
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224 Chapter 9 The biosyntheses of n
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226 Chapter 9 Further reading Gener
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228 Chapter 10 B 1 - H + NH 3 CO
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230 Chapter 10 ‘low-barrier’ +
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232 Chapter 10 H S C 6 H 13 HN His
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234 Chapter 10 O H NH 3 CO 2 − CO
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236 Chapter 10 sub-units. Each sub-
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238 Chapter 10 Further reading Gene
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11 Radicals in Enzyme Catalysis 11.
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242 Chapter 11 CH 2 Co III Ad H OH
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244 Chapter 11 − O 2 C − O CO
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246 Chapter 11 H N H O 734 H N H PF
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248 Chapter 11 H H* + H + H 3 N CO
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250 Chapter 11 O HN NH + H 3 N H 3
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252 Chapter 11 cofactor is involved
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254 Chapter 11 Protein Radicals J.
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256 Chapter 12 self-splicing reacti
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258 Chapter 12 Figure 12.2 Structur
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260 Chapter 12 antigen combining si
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262 Chapter 12 R O OR' OH − R O
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264 Chapter 12 CO 2 − − O 2 C O
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266 Chapter 12 (1) Selective substr
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268 Chapter 12 HO O HO OH HO OH O O
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270 Chapter 12 Problems (1) How rev
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Appendix 1: Cahn-Ingold-Prelog Rule
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Appendix 2: Amino Acid Abbreviation
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276 Appendix 3 Preparation of orang
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278 Appendix 4 (2) Intramolecular a
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280 Appendix 4 from water at a-posi
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282 Appendix 4 Chapter 8 (1) Treat
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284 Appendix 4 (b) Formation of rad
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286 Index b-hydroxydecanoyl thioest
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288 Index glycosylation 26-7 glysop
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290 Index phenylalanine ammonia lya
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292 Index transition states 31-2 an
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