The inactivation of aldehyde dehydrogenase by disulfiram in the presence of glutathione.
نویسنده
چکیده
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 this might arise are discussed.
منابع مشابه
Further 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 کاملMechanism of inactivation of sheep liver cytoplasmic aldehyde dehydrogenase by disulfiram.
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 f...
متن کاملThe 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 کاملHigh concentrations of aldehydes slow the reaction of cytoplasmic aldehyde dehydrogenase with thiol-group modifiers.
High concentrations of aldehydes slow the inactivation of cytoplasmic aldehyde dehydrogenase by disulfiram and also slow the reaction of the enzyme with 2,2'-dithiodipyridine. It is concluded that a low-affinity aldehyde-binding site is probably the site at which thiol-group modifiers react with aldehyde dehydrogenase, as well as being the active site for hydrolysis of 4-nitrophenyl acetate.
متن کاملCarbamoylation of brain glutamate receptors by a disulfiram metabolite.
S-Methyl-N,N-diethylthiolcarbamate sulfoxide (DETC-MeSO), a metabolite of the drug disulfiram, is a selective carbamoylating agent for sulfhydryl groups. Treatment of glutamate receptors isolated from mouse brain with DETC-MeSO blocks glutamate binding. In vivo, carbamoylated glutathione, administered directly to mice or formed by reaction of DETC-MeSO with glutathione in the blood, also blocks...
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عنوان ژورنال:
- The Biochemical journal
دوره 199 1 شماره
صفحات -
تاریخ انتشار 1981