Introduction to Enzyme and Coenzyme Chemistry - E-Library Home

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Enzymatic Hydrolysis and Group Transfer Reactions 117 (3) Cysteine proteases are eVectively inhibited by substrate analogues containing an aldehyde functional group in place of the amide targetted by the enzyme. Suggest a possible mechanism of inactivation. (4) Acetyl CoA is biosynthesised from acetate by diVerent pathways in bacteria versus higher organisms, as shown below. In the case of the bacterial pathway incubation of 18 O-labelled acetate yields one atom of 18 O in the phosphate product, whereas in higher organisms the same experiment yields one atom of 18 O in the adenosine monophosphate (AMP) product. Suggest intermediates and mechanisms for the two pathways. Bacteria: CH 3 CO − 2 + ATP + CoASH (1) acetate kinase (2) phosphotransacetylase CH 3 COSCoA + ADP + P i Higher organisms: CH 3 CO − 2 + ATP + CoASH acetate thiokinase CH 3 COSCoA + AMP + PP i (5) Glycogen is a mammalian polysaccharide consisting of repeating a-1,4-linked d-glucose units. It is stored in liver and muscle and is used as a carbohydrate energy source by the body, being converted to d-glucose when required by the pathway shown below. Suggest mechanisms for each of the enzymes on the pathway. What would be the medical consequences of a genetic defect in muscle glycogen phosphorylase OH O HO O OH O HO glycogen OH O OH O n glycogen phosphorylase Na 2 HPO 4 HO HO OH O OH OPO 2− 3 phosphoglucose isomerase D-glucose HO HO OH O glucose 6-phosphatase HO HO OPO 2− 3 O OH OH P i OH OH
118 Chapter 5 (6) Retaining glycosidases (like lysozyme) are irreversibly inhibited by substrate analogues containing a 2 0 -Xuorine substituent, leading to covalent modiWcation of the enzyme active site. Write a mechanism for this process, and explain why the covalent intermediate is not hydrolysed by the normal reaction pathway of the enzyme. OH 2'-fluoro substrate analogue HO HO O F OAr Further reading General R.H. Abeles, P.A. Frey & W.P. Jencks (1992) Biochemistry. Jones & Bartlett, Boston. C.T. Walsh (1979) Enzymatic Reaction Mechanisms. Freeman, San Francisco. C.H. Wong & G.M. Whitesides (1994) Enzymes in Synthetic Organic Chemistry. Pergamon, Oxford. Serine proteases S. Brenner (1988) The molecular evolution of genes and proteins: a tale of two serines. Nature, 334, 528–30. C.S. Craik, S. Roczniak, C. Largman & W.J. Rutter (1987) The catalytic role of the active site aspartic acid in serine proteases. Science, 237, 909–13. J. Kraut (1977) Serine proteases: structure and mechanism of catalysis. Annu. Rev. Biochem., 46, 331–58. K. Kreutter, A.C.U. Steinmetz, T.C. Liang, M. Prorok, R.H. Abeles & D. Ringe (1994) Three-dimensional structure of chymotrypsin inactivated with (2S)-N-acetyl- L-Ala-L-Phe a-chloroethane: implication for the mechanism of inactivation of serine proteases by chloroketones. Biochemistry, 33, 13792–800. M. Prorok, A. Albeck, B.M. Foxman & R.H. Abeles (1994) Chloroketone hydrolysis by chymotrypsin and N-MeHis57-chymotrypsin: implications for the mechanism of chymotrypsin inactivation by chloroketones. Biochemistry, 33, 9784–90. S. Sprang, T. Standing, R.J. Fletterick, R.M. Stroud, J. Finer-Moore, N.H. Xuong, R. Hamlin, W.J. Rutter, & C.S. Craik (1987) The three-dimensional structure of Asn 102 mutant of trypsin: role of Asp 102 in serine protease catalysis. Science, 237, 905–9. Cysteine proteases F.A. Johnson, S.D. Lewis & J.A. Shafer (1981) Determination of a low pK a for histidine-159 in the S-methylthio derivative of papain by proton NMR spectroscopy. Biochemistry, 20, 44–8. S.D. Lewis, F.A. Johnson & J.A. Schafer (1981) EVect of cysteine-25 on the ionization of histidine-159 in papain as determined by proton NMR spectroscopy. Biochemistry, 20, 48–51.
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 and 14:
2 Chapter 1 H 2 N O NH 2 + H 2 O Ja
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4 Chapter 1 Table 1.1 The vitamins.
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6 Chapter 1 has very diVerent biolo
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2 All Enzymes are Proteins 2.1 Intr
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10 Chapter 2 (Gln). There are three
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12 Chapter 2 AAA Lys ACA Thr AGA Ar
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14 Chapter 2 H N O H N O Figure 2.8
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16 Chapter 2 (a) (b) Figure 2.12 St
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18 Chapter 2 Figure 2.14 Structure
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20 Chapter 2 (a) X Y Enzyme + Subst
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22 Chapter 2 maintaining protein te
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24 Chapter 2 surface glycoprotein g
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26 Chapter 2 O-linked glycosylation
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28 Chapter 2 Metalloproteins I. Ber
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30 Chapter 3 O N H R CO 2 H acylase
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32 Chapter 3 (a) Free energy uncata
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34 Chapter 3 Ester k rel Effective
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36 Chapter 3 3.4 The importance of
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38 Chapter 3 pKa Tyrosine CH 2 O H
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40 Chapter 3 glycoside hydrolysis (
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42 Chapter 3 O O Glu 143 O − R H
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44 Chapter 3 the hydroxyl groups of
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46 Chapter 3 E + S E + S ES' ES ‘
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48 Chapter 3 Examination of protein
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50 Chapter 3 (Note: Similar results
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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
Page 75 and 76:
64 Chapter 4 In general the stereoc
Page 77 and 78: H D T CO 2 H CO − 2 T HO D H −
Page 79 and 80: 68 Chapter 4 4.5 The existence of i
Page 81 and 82: 70 Chapter 4 18O 18O 18 O O P O −
Page 83 and 84: 72 Chapter 4 If a reaction involves
Page 85 and 86: 74 Chapter 4 O D H ketosteroid isom
Page 87 and 88: 76 Chapter 4 Table 4.3 Group speciW
Page 89 and 90: 78 Chapter 4 [S] (mM) Rate of produ
Page 91 and 92: 80 Chapter 4 Enzyme kinetics I.H. S
Page 93 and 94: 82 Chapter 5 O = C NHR peptidase H
Page 95 and 96: 84 Chapter 5 non-speciWc protease c
Page 97 and 98: 86 Chapter 5 His 57 His 57 Asp 102
Page 99 and 100: 88 Chapter 5 Other serine proteases
Page 101 and 102: 90 Chapter 5 Figure 5.8 Structure o
Page 103 and 104: 92 Chapter 5 now predominate Perhap
Page 105 and 106: OH R O Zn 2+ O O O Ph Glu 270 H 2 N
Page 107 and 108: 96 Chapter 5 CASE STUDY: HIV-1 prot
Page 109 and 110: 98 Chapter 5 HO Transition state pe
Page 111 and 112: 100 Chapter 5 The aminoacyl group o
Page 113 and 114: 102 Chapter 5 5.5 Enzymatic phospho
Page 115 and 116: 104 Chapter 5 Figure 5.29 Structure
Page 119 and 120: 108 Chapter 5 Adenosine 5 0 -tripho
Page 121 and 122: 110 Chapter 5 functional group. Gly
Page 123 and 124: 112 Chapter 5 CH 2 OH O RO HO OH O
Page 125 and 126: 114 Chapter 5 to these atoms that t
Page 127: 116 Chapter 5 Problems (1) Using pa
Page 131 and 132: 120 Chapter 5 J.R. Knowles (1980) E
Page 133 and 134: 122 Chapter 6 +1.0 Redox potential
Page 135 and 136: Table 6.1 Classes of redox enzymes.
Page 137 and 138: 126 Chapter 6 An important point is
Page 139 and 140: 128 Chapter 6 O H − OH − O OH H
Page 141 and 142: 130 Chapter 6 one-electron transfer
Page 143 and 144: 132 Chapter 6 (a) R N H + N O R N H
Page 145 and 146: 134 Chapter 6 Inactivation by trany
Page 149 and 150: 138 Chapter 6 (a) (b) Figure 6.23 S
Page 151 and 152: 140 Chapter 6 glutathione called tr
Page 153 and 154: 142 Chapter 6 neither has a stable
Page 155 and 156: 144 Chapter 6 of the haem cofactor
Page 157 and 158: 146 Chapter 6 Figure 6.33 Active si
Page 159 and 160: 148 Chapter 6 HO H N N O O H N prol
Page 161 and 162: 150 Chapter 6 R R R O 2 , Fe 2+ O O
Page 163 and 164: 152 Chapter 6 CoA. Explain these re
Page 165 and 166: 154 Chapter 6 NADH models O. Almars
Page 167 and 168: 7 Enzymatic Carbon-Carbon Bond Form
Page 169 and 170: 158 Chapter 7 O H − OH O − O H
Page 173 and 174: 162 Chapter 7 Figure 7.6 Active sit
Page 175 and 176: 164 Chapter 7 7.3 Claisen enzymes I
Page 177 and 178: 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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184 Chapter 7 Figure 7.36 Structure
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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 +
Page 201 and 202:
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
Page 211 and 212:
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
Page 219 and 220:
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 +
Page 225 and 226:
214 Chapter 9 - BEnz CO − 2 Cl H
Page 227 and 228:
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
Page 283 and 284:
Appendix 1: Cahn-Ingold-Prelog Rule
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Appendix 2: Amino Acid Abbreviation
Page 287 and 288:
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
Page 297 and 298:
286 Index b-hydroxydecanoyl thioest
Page 299 and 300:
288 Index glycosylation 26-7 glysop
Page 301 and 302:
290 Index phenylalanine ammonia lya
Page 303:
292 Index transition states 31-2 an
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