Studies on the interaction between disulfiram and sheep liver cytoplasmic aldehyde dehydrogenase. 1978

T M Kitson

The effect of disulfiram, [1-14C]disulfiram and some other thiol reagents on the activity of cytoplasmic aldehyde dehydrogenase from sheep liver was studied. The results are consistent with a rapid covalent interaction between disulfiram and the enzyme, and inconsistent with the notion that disulfiram is a reversible competitive inhibitor of cytoplasmic aldehyde dehydrogenase. There is a non-linear relationship between loss of about 90% of the enzyme activity and amount of disulfiram added; possible reasons for this are discussed. The remaining approx. 10% of activity is relatively insensitive to disulfiram. It is found that modification of only a small number of groups (one to two) per tetrameric enzyme molecule is responsible for the observed loss of activity. The dehydrogenase activity of the enzyme is affected more severely by disulfiram than is the esterase activity. Negatively charged thiol reagents have little or no effect on cytoplasmic aldehyde dehydrogenase. 2,2'-Dithiodipyridine is an activator of the enzyme.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D002621 Chemistry A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
D003593 Cytoplasm The part of a cell that contains the CYTOSOL and small structures excluding the CELL NUCLEUS; MITOCHONDRIA; and large VACUOLES. (Glick, Glossary of Biochemistry and Molecular Biology, 1990) Protoplasm,Cytoplasms,Protoplasms
D004221 Disulfiram A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase. Tetraethylthiuram Disulfide,Alcophobin,Antabus,Antabuse,Anticol,Bis(diethylthiocarbamoyl) Disulfide,Dicupral,Esperal,Tetraethylthioperoxydicarbonic Diamide, ((H2N)C(S))2S2,Teturam,Disulfide, Tetraethylthiuram
D000445 Aldehyde Oxidoreductases Oxidoreductases that are specific for ALDEHYDES. Aldehyde Oxidoreductase,Oxidoreductase, Aldehyde,Oxidoreductases, Aldehyde
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012756 Sheep Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS. Ovis,Sheep, Dall,Dall Sheep,Ovis dalli
D013439 Sulfhydryl Reagents Chemical agents that react with SH groups. This is a chemically diverse group that is used for a variety of purposes. Among these are enzyme inhibition, enzyme reactivation or protection, and labelling. SH-Reagents,Sulfhydryl Compound Antagonists,Sulfhydryl Compound Inhibitors,Thiol Reagents,Sulfhydryl Compounds Antagonists,Sulfhydryl Compounds Inhibitors,Antagonists, Sulfhydryl Compound,Antagonists, Sulfhydryl Compounds,Compound Antagonists, Sulfhydryl,Compound Inhibitors, Sulfhydryl,Inhibitors, Sulfhydryl Compound,Inhibitors, Sulfhydryl Compounds,Reagents, Sulfhydryl,Reagents, Thiol,SH Reagents
D055598 Chemical Phenomena The composition, structure, conformation, and properties of atoms and molecules, and their reaction and interaction processes. Chemical Concepts,Chemical Processes,Physical Chemistry Concepts,Physical Chemistry Processes,Physicochemical Concepts,Physicochemical Phenomena,Physicochemical Processes,Chemical Phenomenon,Chemical Process,Physical Chemistry Phenomena,Physical Chemistry Process,Physicochemical Phenomenon,Physicochemical Process,Chemical Concept,Chemistry Process, Physical,Chemistry Processes, Physical,Concept, Chemical,Concept, Physical Chemistry,Concept, Physicochemical,Concepts, Chemical,Concepts, Physical Chemistry,Concepts, Physicochemical,Phenomena, Chemical,Phenomena, Physical Chemistry,Phenomena, Physicochemical,Phenomenon, Chemical,Phenomenon, Physicochemical,Physical Chemistry Concept,Physicochemical Concept,Process, Chemical,Process, Physical Chemistry,Process, Physicochemical,Processes, Chemical,Processes, Physical Chemistry,Processes, Physicochemical

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