[Studies on the biological effects of disulufiram--effect of an active metabolite of disulfiram on the activity of delta-aminolevulinic acid synthetase].

The effect of diethyldithiocarbamic acid methyl eater (Me-DDC), a metabolite of disulfiram, on hepatic delta-aminolevulinic acid (ALA) synthetase activity was investigated in male rats. The results obtained were as follows: 1) When rats were given intraperitoneally Me-DDC at the dose levels of 0.0625, 0.125, 0.25 and 0.50 mmol/kg, the activity of ALA synthetase showed a maximum level at a dose of 0.125 mmol/kg. 2) ALA synthetase activity increased rapidly and reached a maximum level in about 2 hr after the intraperitoneal administration of Me-DDC (0.125 mmol/kg). 3) Pretreatment with phenobarbital (an inducer of drug metabolizing enzymes) tended to depress the increase of ALA synthetase caused by Me-DDC, whereas pretreatment with SKF 525-A (an inhibitor of drug metabolizing enzymes) stimulated slightly the Me-DDC-induced increased of the enzyme. 4) The apparent Km value of the enzyme for glycine did not change but the Vmax value increased in Me-DDC-treated rats. 5) Actinomycin D (a potent inhibitor of DNA-dependent synthesis of RNA), when administered to rats before Me-DDC, completely prevented the induction of ALA synthetase caused by the latter compound. 6) Pretreatment with phorone (a glutathion depletor) 4 hr prior to the administration of Me-DDC completely inhibited the Me-DDC-induced increase of ALA synthetase.