Microbiological studies with thioctic acid analogues. II. Enzymatic evidence for interference with acetyl transfer by 6-ethyl-8-mercaptooctanoic acid.

6-Ethyl-8-mercaptooctanoic acid, which bears a close chemical relationship to two functional forms of thioctic acid, 6,8-dimercaptooetanoic acid and 6-S-acetyl-6,8-dimercaptooetanoic acid, was found to be toxic for the growth of several microorganisms (Broquist and Stiffey, 1958). These effects were not nullified by thioctic acid, but were reversed competitively by a number of fatty acids including aeetate. The possibility suggested itself that 6-ethyl-8-mercaptooctanoic acid might be inhibiting growth by interfering with one of the functional forms of thioctic acid concerned in acetyl transfer. To test this hypothesis, the effect of 6-ethyl-8-mercaptooctanoic acid and related thioctic acid analogues on several acetate-generating or acetate-transferring enzyme systems of bacterial origin has been investigated. Some evidence has been found that the inhibitory effects of 6-ethyl-8-mercaptooctanoic acid on certain bacterial enzyme systems can be counteracted by 6,8-dimercaptooetanoic aci(d and to a lesser extent by coenzyme A.