Abstract
The El isoenzyme of human liver aldehyde dehydrogenase (Km acetaldehyde = 30uM, pH 7.0), when incubated with disulfiram at a stoichiometry of four moles disulfiram/tetrameric El, is immediately inhibited to within 10% of control activity. The inhibition is reversed by 0.1% (v/v) mercaptoethanol, indicating disulfide bridge formation. An indirect attempt to locate, on maps, a peptide binding disulfiram has yielded inconsistent results. Iodoacetamide inhibits El slowly; inhibition is facilitated in the presence of NAD, resulting in loss of ca. 90% of control activity. Incubation with 14C iodoacetamide labels a 16,000 dalton CNBr peptide, and a ca. 4,000 dalton tryptic cleavage product. These fragments can be equated with those which have been suggested by disulfiram.
Financial support of USPHS grants AA05097 and AA00186 is gratefully acknowledged.
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Hempel, J.D., Vallari, R.C., Pietruszko, R. (1980). On the Interaction of Human Liver Aldehyde Dehydrogenase E1 Isoenzyme with Disulfiram and Iodoacetamide. In: Thurman, R.G. (eds) Alcohol and Aldehyde Metabolizing Systems-IV. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1419-7_5
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DOI: https://doi.org/10.1007/978-1-4757-1419-7_5
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