3-Oxoacyl-CoA transferase

Example 3-Oxoacyl-CoA transferase (Y = —S—CoA) B. Addition to a carbonyl group aldol condensation... 

Oxoacyl-CoA transferase (see fig. 18.8) is involved in the transfer of a CoASH from succinyl-CoA to acetoacetate to produce succinate and aceto-acetyl-CoA. A cursory examination of this reaction suggests a simple transfer of the CoA moiety. However, it is soon realized that the loss of an oxygen by the acetoacetate and the gain of an oxygen by the succinyl group present a dilemma. Produce a rational mechanism that explains the preservation of the thio-ester energy and solves this dilemma. Hint Consider a succinyl phosphate intermediate. 

Keto acidosis may occur in infants as a result of specific genetic defects, in addition to its occurrence in association with several other organic acidurias, for example propionic acidaemia (ketotic hyperglycinaemia). Chapter 10, Section 10.4.1 on 2-methylacetoacetyl-CoA thiolase deficiency also discussed a report by Robinson et al. (1979) of a patient with apparent combined deficiencies of this enzyme and of 3-oxoacyl-CoA thiolase, which they considered to be identical enzymes. A report of a case of specific 3-oxoacyl-CoA thiolase deficiency has increased interest in these enzymes as causes of congenital keto acidosis, and these are discussed further below, as are patients with a different cause of a similar biochemical condition, succinyl-CoA 3-keto acid-CoA transferase deficiency. 

Spatially, the enzyme activities are arranged into three different domains. Domain 1 catalyzes the entry of the substrates acetyl CoA and malonyl CoA by [ACPj-S-acetyltransferase [1] and [ACPJ-Smalonyl transferase [2] and subsequent condensation of the two partners by 3-oxoacyl-[ACP] synthase [3]. Domain 2 catalyzes the conversion of the 3-0X0 group to a CH2 group by 3-oxoacyl-[ACP]-reductase [4], 3-hydroxyacyl-[ACP -dehydratase [5], and enoyl-[ACP]-re-... 

Figure 3.2 Enzyme systems associated with the de novo synthesis of fatty acids in the plastid. (a) Acetyl-CoA carboxylase (EC 6.4.1.2) (b) [acyl-carrier protein] (ACP) acetyl-transferase (EC 2.3.1.38) (c) [ACP] malonyltransferase (EC 2.3.1.39) (dl) 3-oxoacyl-[ACP] synthase I (d2) 3-oxoacyl-[ACP] synthase II (EC 2.3.1.41) (d3) 3-oxoacyl-[ACP] synthase III (e) 3-oxoacyl-[ACP] reductase (EC 1.1.1.100) (f) 3-hydroxyacyl-[ACP] dehydratase (g) enoyl-[ACP] reductase (EC 1.3.1.9/10) (d)-(g) constitutes fatty acid synthase...

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