Thiol transacetylase

The really unique reaction of the lipoate centre in ct-keto acid metabolism is the oxidative thioester formation from a thiamine-coordinated active aldehyde . Thiol transacetylase and dithiol-disulphide oxidation reduction roles are well-known attributes of other biological thiols. Unfortunately mechanistic studies on this reductive acylation of a cyclic disulphide have so far received little attention. Proposals that a lipoic acid-thiamine pyrophosphate compound was the functional entity in a-keto acid oxidation have been completely abandoned, but data supporting this concept remain unexplained. Investigations in this area might have some relevance for the reductive acylation process. 

The thiol transacetylase that catalyzes this reaction has been partially purified from extracts of E. coli by Hager and Gunsalus (personal communication), and was shown to be relatively specific. We have recently discovered enzymes in extracts of C. kluyveri (47) and in pigeon-liver extracts (48) that catalyze similar acetyl transfers from acetyl-SCoA to 2-mercap-toethanol, thioglycollate, reduced lipoic acid, and hydrogen sulfide however, GSH and cysteine are relatively inert as acetyl acceptors. It remains to be demonstrated if one or more enzymes are involved in these acyl-transfer reactions. The enzyme-catalyzed reactions are to be differentiated from the nonenzymatic reactions in that they occur readily in more dilute solutions and also at neutral to slightly acid pH. 

Figure 12.17 Important targets for the generation of an L-cysteine production strain. Mutant proteins are marked with an asterisk. Exp. cysteine export proteins. SerA 3-phosphoglycerate dehydrogenase. CysE serine transacetylase. CysB transcriptional activator of the cystein regulon. CysK O-acetyl-L-serine (thiol)-lyase A. CysM O-acetyl-L-serine (thiol)-lyase B.

Fig. 3. Regulation of the bound pathway for the assimilation of sulfate into cysteine and associated processes. Carrier refers to an endogenous thiol of uncertain identity in higher plants. Enzymes associated with the sulfate assimilation pathway and the synthesis of O-acetylseiine are (1) high-ailinity sulfate uptake mechanism, (2) ATP-sulfurylase, (3) adenosine S -phosphosulfate (APS) sulfotransferase, (4) organic thiosulfate reductase, (5) cysteine synthase, and (6) serine transacetylase. Cysteine sulfhydrase (7), an enzyme of cysteine catabolism, and nitrate reductase (8), the first enzyme of the nitrate assimilation pathway, are also shown. Inhibitory control of the pathways is shown by discontinuous lines (----) and enhancement by continuous lines (------).

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