Aldehyde oxidation. II. Evidence for closely juxtaposed sulfhydryl groups on dehydrogenases.

The reactivity of mercaptans with carbonyl groups has often suggested the involvement of such combinations in the enzymatic transformation of compounds containing the carbonyl function. Although the details of the interaction between protein and substrate remain a matter of controversy, there can be no denial of the intimate involvement of protein sulfhydry1 groups with substrate in at least several cases (2). With brain and several of the bacterial preparations (3), the sensitivity of the pyruvate oxidation system to arsenite (4-6), the isolation and identification of lipoic acid as a cofactor (7), and the separation of the manifold factors involved in pyruvate oxidation have established a dimercaptan as participating in a-keto acid oxidation (3). The finding (8) that low concentrations of arsenite were inhibitory to the oxidation of aldehydes by an enzyme from Pseudomonas JEuorescens prompted the investigation of other aldehyde dehydrogenases, which have been found to be similar in this respect. Indeed, the sensitivity of aldehyde dehydrogenases to arsenite appears to be the rule and suggests the involvement of two sulfhydryl groups in close juxtaposition with a role in the catalysis of aldehyde oxidation. The present report is concerned with evidence bearing on this concept.