In vitro inactivation of hepatic alcohol dehydrogenase and aldehyde dehydrogenases from rats by dithiocarbamates with or without metals.

Abstract

Alcohol dehydrogenases is localized mainly in the hepatic cytoplasm. Aldehyde dehydrogenases are bound predominantly to the hepatic mitochondrial and endoplasmic reticular membranes; a small part of their total activity is measured in the cytosol. ALDH catalyses the oxidation of acetaldehyde to acetic acid and the metabolism of endogenous or exogenous aldehydes. The goal of the present investigation was to examine in vitro the possible interaction of metal containing dithiocarbamates with the activity of ALDH isolated from rat livers in comparison with that of dithiocarbamates without metals. In addition, the elucidation of an inhibitory effect on isolated liver ADH possibly caused by dithiocarbamates with or without metals could help to explain a previously found delay of ethanol elimination from rat blood. To this end the following substances were tested: The dimers TMTD and TETD, the monomers dimethyldithiocarbamate (DMDC) as sodium salt or as zinc salt and diethyldithiocarbamate (DEDC) as sodium salt, as well as the related compounds tetramethylthiuram monosulfide (TMTM), manganese(II)-(N,N'-ethylenebis(dithiocarbamate)), and zinc-(N,N'-ethylenebis(dithiocarbamate)).