Stimulation of Alcohol Dehydrogenase by Dimethyldithiocarbamate
Abstract
On an investigation of the mechanism of epoxytrichothecene inhibition of yeast alcohol dehydrogenase (YADH) reaction, we have accidentally found that dimethyldithiocarbamate (DMDTC) was an effective activator of the enzyme. DMDTC is a vulcanizing accelerator used extensively in manufacturing of rubber products such as stoppers. The compound is an analog of diethyldithiocarbamate (DEDTC), a metabolite of disulfiram (tetraethylthiuram disulfide, antabuse). Disulfiram is a well known drug for treating alcoholism because of its inhibitory effect on aldehyde dehydrogenases. In vivo, DEDTC is as effective an inhibitor of aldehyde dehydrogenase as disulfiram, but has little effect on the enzyme activity in vitro. Similarly, we can not demonstrate any significant effect of DMDTC on aldehyde dehydrogenase by this compound. The kinetic data obtained from our present investigation indicated that the DMDTC stimulation reaction followed an ordered bireactant mechanism in which DMDTC and NAD binding to the enzyme molecules is in an obligate order, i.e., DMDTC binding followed by NAD binding. On the other hand, evidence of formation of a substrate-YADH-DMDTC transitory complex with enhanced enzyme activity can also be shown from the kinetic data that we obtained. The results of our present investigation on the kinetics of the DMDTC stimulation of the YADH reaction will be presented in this paper.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1987
- Accession Number
- ADA187125
Entities
People
- Homer R. Yeh