Acetoacetate decarboxylase borohydride

BOROHYDRIDE REDUCTION ACETAZOLAMIDE Acetic acid, autoprotolysis constant, AUTOPROTOLYSIS ACETOACETATE DECARBOXYLASE Acetoacetate decarboxylase reduction, BOROHYDRIDE REDUCTION ACETOLACTATE SYNTHASE Acetone,... 

In 1962 too, Fridovich showed that the addition of sodium borohydride to a mixture of acetoacetate decarboxylase and acetoacetate inactivates the enzyme, whereas the addition of borohydride to a buffered solution of the enzyme alone has no effect on the rate at which it can promote the decarboxylation of acetoacetate (Fridovich and Westheimer, 1962) this work confirmed the ketimine mechanism that had previously been advanced for the decarboxylation. Subsequent work (beyond the scope of this review) showed that the reaction product, on hydrolysis, yielded e-isopropyllysine [8], formed by the reduction of the ketimine of acetone (11), and control experiments showed that this ketimine was actually an intermediate in the enzymic pathway, as had been postulated (Warren et al., 1966). 

A variety of /8-diketones have been demonstrated to be very effective inhibitors of acetoacetate decarboxylase [83]. Although they bind tightly to the active site they are not reduced by borohydride. Corresponding a- or y-diketones are not inhibitory [84]. Acetopyruvate, for example, inhibits competitively with respect to acetoacetate with... 

Paracatalytic enzyme modification is a new type of catalysis-linked and, hence, substrate-dependent enzyme modification. In all instances in which the substrate promotes inactivation of an enzyme by a chemical reagent, particularly by an oxidant, paracatalsrtic modification should he considered to be the underlying mechanism. In contrast to ligand-induced and syncatalytic modifications, paracatalytic modification involves a direct chemical interaction between enzyme-activated substrate and extrinsic reagent. In this respect, it is similar to the chemical trapping of covalent enzyme-substrate intermediates, e.g., the reduction of enzyme-substrate Schiff bases by sodium borohydride in class I fructose-l,6-bis-phosphate aldolases - or in acetoacetate decarboxylase. ... 

This enzyme catalyses the decarboxylation of the ) -ketoacid oxaloacetate, with the same stoichiometry as acetoacetate decarboxylase. The former however, requires a Mn ion for activity and is insensitive to the action of sodium borohydride. This duality of mechanism is not unlike the one observed for enzymatic aldol condensation, where enzymes of Class 1 react by forming Schiff-base intermediates, whereas enzymes of Class II show metal ion requirements [47]. Oxaloacetate decarboxylase from cod also catalyses the reduction by borohydride of the enzymatic reaction product pyruvate. This is evidenced by the accumulation of D-lactate in presence of enzyme, reducing agent, and manganous ions. It has been proposed that both reduction and decarboxylation occur by way of an enzyme-metal ion-substrate complex in which the metal ion acts as an electron sink, thereby stabilizing the enolate ion formed in the decarboxylation reaction [48] ... 

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