INHIBITORY ACTION OF DITHIOCARBAMATES ON ENZYMES OF ANIMAL TISSUES
Abstract
A study of the effects of derivatives of dithiocarbamic acid was conducted in an attempt to obtain information on the biochemical mechanisms responsible for their toxicity and their radioprotective action. The compounds employed for this study were sodium diethyldithiocarbamate, diethylammonium diethyldithiocarbamate, dimethylammonium dimethyldithiocarbamate, and bis(dimethyldithiocarbamyl) disulfide. Attention was focused on the actions of these compounds on the oxidative phase of intermediary carbohydrate metabolism. All of the compounds were effective inhibitors of the tricarboxylic acid cycle of animal tissues in vitro as evidenced by inhibition of oxygen consumption, citrate synthesis, pyruvic dehydrogenase, alpha-ketoglutarate oxidase, and succinic dehydrogenase. The salts of dithiocarbamic acid were effective inhibitors of these enzymatic reactions in vivo but the disulfide, which lacks radioprotective activity, did not inhibit these reactions in the intact animal. The salts of dithiocarbamic acid also rapidly reduced cytochrome c and inhibited tyrosinase activity in vitro. The results of this investigation suggest that the acute mammalian toxicity of the dithiocarbamates is the result of their strong inhibitory action on enzymes that require sulfhydryl groups for activity. (Author)
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1961
- Accession Number
- AD0262950
Entities
People
- Ann B. Raymund
- Bernard E. Hietbrink
- Kenneth P. Dubois
Organizations
- United States Air Force School of Aerospace Medicine