STUDIES ON POSSIBLE MECHANISMS FOR THE INTERACTION BETWEEN CYANAMIDE AND ALDEHYDE DEHYDROGENASE

Cyanamide is known to interfere with the metabolism of alcohol by decreasing the activity of aldehyde dehydrogenase in vivo, thereby leading to an accumulation of acetaldehyde following the ingestion of ethanol. We have studied various mechanisms for the chemical interaction between aldehyde dehydrogenase and cyanamide (or some of its possible metabolites). Cyanamide was shown to react under physiological conditions with amino and thiol groups, forming guanidino and isothiouronium compounds respectively. However, it was found that the enzyme is not appreciably affected in vitro by high concentrations of cyanamide. Dicyandiamide and the aminoethylisothiouronium ion (AET) also have no effect in vitro. It was postulated that the pathway of in vivo enzyme modification by cyanamide may involve thiourea (formed by breakdown of isothiouronium compounds) and formamidine disulphide (an oxidation product of thiourea). However, although the disulphide is a moderately-effective inactivator of aldehyde dehydrogenase in vitro, administration of thiourea or AET to rats does not result in any significant loss of aldehyde dehydrogenase activity in either the cytoplasm or the mitochondria. © 1979.