On the interaction of human liver aldehyde dehydrogenase E1 isoenzyme with disulfiram and iodoacetamide.

The E1 isoenzyme of human liver aldehyde dehydrogenase (Km acetaldehyde = 30uM, pH 7.0), when incubated with disulfiram at a stoichiometry of four moles disulfiram/tetrameric E1, 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 E1 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.