Crotonase

FIGURE 24.15 The conversion of trans- and m-enoyl CoA derivatives to l- and d-/3-hydroxyacyl CoA, respectively. These reactions are catalyzed by enoyl-CoA hydratases (also called crotonases), enzymes that vary in their acyl-chain length specificity. A recently discovered enzyme converts ram-enoyl-CoA directly to D-/3-hydroxyacyl-CoA. 

CROTONASE SUPERFAMILY ADDITION REACTION Additive feedback inhibition,... 

PERIODATE CLEAVAGE MALAPRADE REACTION Carbon-carbon bond formation, CROTONASE SUPERFAMILY CARBON-14 ( C)... 

DIHYDROXYACETONE PHOSPHATE ACYLTRANSFERASE ENOYL-CoA HYDRATASE (or, CROTONASE)... 

The active site of enoyl-CoA isomerase is a good example of an active site built on the framework of the crotonase fold. It is now weU established that this crotonase fold provides an active site framework that has been used by Nature for a wide range of different chemical reactions, as reviewed recently [73, 85]. The reaction of this enoyl-CoA isomerase is initiated by a catalytic base, Glul36, abstracting a proton from the Ca-carbon, generating the negatively charged enolate... 

ClpP/crotonase ClpP/crotonase Crotonas e-like... 

Enoyl-CoA hydratase. A specific example of the reaction in Eq. 13-6 is the addition of water to fra s-a,P-unsaturated CoA derivatives (Eq. 13-7). It is catalyzed by enoyl-CoA hydratase (crotonase) from mitochondria and is a step in the P oxidation of fatty acids (Fig. 10-4). 

Creutzfeldt-Jakob disease 248 Crick, Francis H. C. 84, 200 Cristae of mitochondria 14 Crossing-over 18 Crosslinking 79 Crotonase. See Enoyl hydratase Crowfoot Hodgkin, Dorothy M. 84 Cruciform structure in nucleic acids 229 Crustacea 24 Cruzain 619 Cryoenzymology 469 elastase 616 Cryoprotectants 191 Crystallins 169 Crystallography 131-137 electron 131 X-ray 132-137 Crystals, liquid 392-394 Crystal systems 133 Cubic symmetry... 

In the Briggs-Maldane mechanism, when k2 is much greater than k-i, kcJKM is equal to kx, the rate constant for the association of enzyme and substrate. It is shown in Chapter 4 that association rate constants should be on the order of 108 s l M l. This leads to a diagnostic test for the Briggs-Haldane mechanism the value of kaJKu is about 107 to 108 s-1 M-1. Catalase, acetylcholinesterase, carbonic anhydrase, crotonase, fumarase, and triosephosphate isomerase all exhibit Briggs-Haldane kinetics by this criterion (see Chapter 4, Table 4.4). 

Cost-selectivity equation 395-399 Coupled assays 196 Covalent catalysis 62, 77-85 see also nucleophilic catalysis Creatine kinase 264, 266 Crotonase 108, 166 Cryoenzymology 40 Crystalline enzymes activity 45 water content 39 Curie 196... 

Methylcrotonyl CoA Carboxylase Methylcrotonyl CoA carboxylase catalyzes the conversion of methylcrotonyl CoA, arising from the catabolism of leucine, to methylglutaconyl CoA. This in turn undergoes hydroxy-lation catalyzed by crotonase, yielding hydroxymethyl-glutaryl CoA, which is cleaved to acetyl CoA and acetoacetate. 

Certain CoA thioester using enzymes catalyze reactions at the fS-carbon or other carbons of the acyl group more distant from the thioester functionality. The fatty acid fi-oxidation cycle provides some examples (Fig. 3). Fatty acids 7 enter the cycle by initial conversion to the CoA ester 8, which is then oxidized to the a,P-unsaturated thioester 9 by a flavin-dependent enzyme. Addition of water to the double bond to form the fi-hydroxy thioester 10 is catalyzed by the enzyme crotonase, which is the centerpiece of the crotonase superfamily of enzymes that catalyze related reactions (37), which is followed by oxidation of the alcohol to form the fi-keto thioester 11. A retro-Claisen reaction catalyzed by thiolase forms acetyl-CoA 12 along with a new acyl-CoA 13 having a carbon chain two carbons shorter than in the initial or previous cycle. 

Figure 3 The fatty acid p-oxidation cycle. El acylcoenzyme A synthetase E2 acylcoenzyme A dehydrogenase E3 enoylcoenzyme A hydratase (crotonase) E4 p-hydroxyacylcoenzyme A dehydrogenase E5 thiolase.

The oxoester analog of crotonyl-CoA 26 shown in Fig. 5 was used as an alternative substrate for crotonase and exhibited about 300-fold decreased activity relative to the natural... 

Holden HM, Banning MM, Haller T, Gerlt JA. The crotonase superfamily divergently related enzymes that catalyze different reactions involving acyl coenzyme A thioesters. Acc. Chem. Res. 2001 34 145-157. 

---