Identification of aldehyde dehydrogenase resistant to cyanamide and disulfiram inhibition

A small number of Wistar rats from our breeding colony was identified whose mitochondrial low-K_m aldehyde dehydrogenase (ALDH) was resistant to inactivation by low (2.5 μM) concentrations of cyanamide, termed “resistant” by contrast to the typical animal labeled “sensitive.” Resistance could be due either to a lack of the hypothesized cyanamide-converting enzyme (catalase) or to the presence of different forms of ALDH. ALDH purified by affinity chromatography from either type of animal was not inhibited by cyanamide alone. Addition of intact “sensitive” mitochondria with cyanamide caused a great inhibition of purified cyanamide-sensitive ALDH but not of resistant ALDH. Similar results were obtained when catalase was used to convert cyanamide to its reactive derivative. Furthermore, disulfiram was observed to be less effective in inhibiting the cyanamide-resistant ALDH. These combined results are interpreted as indicating that resistance to cyanamide inhibition is due to a difference in ALDH isozymes and not to an artifact of the isolation process or to the absence of the cyanamide-activating enzyme.