Mechanism of inactivation of sheep liver cytoplasmic aldehyde dehydrogenase by disulfiram.
نویسنده
چکیده
Stoicheiometric amounts of [14C]disulfiram react rapidly with sheep liver cytoplasmic aldehyde dehydrogenase to give loss of catalytic activity and incorporation of the expected amount of radioactivity. In a subsequent slower reaction the label is lost from the enzyme without re-emergence of enzymic activity. The results imply that in vivo disulfiram may act as an oxidation-reduction catalyst for the inactivation of aldehyde dehydrogenase.
منابع مشابه
The effect of disulfiram on the aldehyde dehydrogenases of sheep liver.
1. The effect of disulfiram on the activity of the cytoplasmic and mitochondrial aldehyde dehydrogenases of sheep liver was studied. 2. Disulfiram causes an immediate inhibition of the enzyme reaction. The effect on the cytoplasmic enzyme is much greater than on the mitochondrial enzyme. 3. In both cases, the initial partial inhibition is followed by a gradual irreversible loss of activity. 4. ...
متن کاملFurther studies of the action of disulfiram and 2,2'-dithiodipyridine on the dehydrogenase and esterase activities of sheep liver cytoplasmic aldehyde dehydrogenase.
1. Pre-modification of cytoplasmic aldehyde dehydrogenase by disulfiram results in the same extent of inactivation when the enzyme is subsequently assayed as a dehydrogenase or as an esterase. 2. 4-Nitrophenyl acetate protects the enzyme against inactivation by disulfiram, particularly well in the absence of NAD+. Some protection is also provided by chloral hydrate and indol-3-ylacetaldehyde (i...
متن کاملIdentification of a catalytically essential nucleophilic residue in sheep liver cytoplasmic aldehyde dehydrogenase.
Sheep liver cytoplasmic aldehyde dehydrogenase was labelled by reaction with the substrate p-nitrophenyl di[14C]methylcarbamate. After tryptic digestion and peptide fractionation the labelled residue was identified as Cys-302. This is the first unequivocal identification of the essential enzymic nucleophile in the esterase activity of aldehyde dehydrogenase. By implication, Cys-302 is probably ...
متن کاملEffect of some thiocarbamate compounds on aldehyde dehydrogenase and implications for the disulfiram ethanol reaction.
The effects of S-methyl diethyldithiocarbamate, S-methyl diethylmonothiocarbamate and bis(diethylcarbamoyl) disulphide on sheep liver cytoplasmic aldehyde dehydrogenase were investigated in vitro. The first compound has negligible effect. The second one is a weak inhibitor of the esterase activity of the enzyme and a weaker inhibitor of the dehydrogenase activity. A very low concentration of th...
متن کاملThe inactivation of aldehyde dehydrogenase by disulfiram in the presence of glutathione.
It is shown that in vitro glutathione provides little protection of cytoplasmic aldehyde dehydrogenase against the inactivatory action of disulfiram. This observation provides support for the current explanation of how disulfiram acts in vivo. The results show that the disulfiram-sensitive thiol groups of aldehyde dehydrogenase have an unusually high reactivity; possible mechanisms by which thi...
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عنوان ژورنال:
- The Biochemical journal
دوره 213 2 شماره
صفحات -
تاریخ انتشار 1983