The influence of allyl isopropyl acetamide on d-aminolevulinic acid synthetase and cytochrome P-450.

Allyl isopropyl acetamide (AIA) is believed to destroy P-450 and to enhance the d-aminolevulinic acid synthetase (ALAS) activity by lowering the heme pool of the liver parenchymal cell, in this way weakening the negative feed back mechanism, which regulates ALAS synthesis at the translational level. Dose and time dependence of the AIA influence on cytochrome P-450 concentration and P-450 activity argues against this theory, supporting the hypothesis that AIA destroys P-450 only after administration of higher doses (> 300 mg/kg i. p.), but does not influence or even enhances P-450 concentration when given in lower doses which exert an increase in ALAS activity. 25--100 mg/kg AIA i. p. have no significant effect on ALAS activity, 200 mg/kg and higher doses up to 400 mg/kg cause dose-dependent increases in ALAS activity.