Effects of disulfiram, cyanamide and 1-aminocyclopropanol on the aldehyde dehydrogenase activity in human erythrocytes and leukocytes.
The effects of the aldehyde dehydrogenase (ALDH; EC 1.2.1.3) inhibitors disulfiram, cyanamide and 1-aminocyclopropanol (ACP) on the ALDH activities in human erythrocytes and leukocytes were studied. Assays were performed by incubating intact or sonicated blood cells in the presence of different concentrations of the inhibitors, using 3,4-dihydroxyphenylacetaldehyde, the aldehyde derived from dopamine oxidation, as the substrate. The amount of acid metabolite formed was measured using high-performance liquid chromatography with electrochemical detection. The erythrocyte ALDH was extremely sensitive to disulfiram, and only about 0.5 microM was needed to cause a 50% inhibition of the activity. The leukocyte activity was less sensitive, and showed a similar degree of inhibition at an 100-fold higher concentration of disulfiram. Cyanamide and ACP were both potent inactivators of the leukocyte ALDH activity, giving a 50% inhibition at concentrations of 10 and 50 microM, respectively, whereas the erythrocyte activity was much less affected. Diethyldithiocarbamate, the reduced metabolite of disulfiram, and coprine, from which ACP is derived, were much less effective inhibitors of the erythrocyte and leukocyte ALDH activities than were disulfiram and ACP.
Helander
A
A
Department of Zoophysiology, Uppsala University, Sweden.
Tottmar
O
O
D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors* / Q000097:blood; D003484:Cyanamide / Q000494:pharmacology*; D003486:Cyanides / Q000494:pharmacology*; D003521:Cyclopropanes / Q000494:pharmacology*; D004221:Disulfiram / Q000494:pharmacology*; D004050:Ditiocarb / Q000494:pharmacology; D004912:Erythrocytes / Q000201:enzymology*; D005973:Glutamine / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*
D003486:Cyanides; D003521:Cyclopropanes; C014318:1-aminocyclopropanol; D005973:Glutamine; C014423:coprine; D003484:Cyanamide; D004050:Ditiocarb; D000444:Aldehyde Dehydrogenase; D004221:Disulfiram