Mechanism of Allylisopropylacetamide-induced Increase of δ-Aminolevulinate Synthetase in Liver Mitochondria

Abstract

The AIA-induced increase of ALA synthetase in rat-liver mitochondria was greatly suppressed by the administration of hemin, hemoglobin or bilirubin. The effects of bilirubin were very similar to those of hemin, suggesting that the mechanisms by which hemin and bilirubin affect enzyme synthesis may be similar, if not identical. The mitomycinsensitive second phase of the induction appeared to be more susceptible to hemin and bilirubin than the mitomycin-insensitive first phase. Administration of hemin or bilirubin also reduced the ALA synthetase level in control rats which did not receive AIA. Evidence is presented that the observed inhibition of ALA synthetase induction might be due to inhibition of synthesis of messenger RNA. Hemin and bilirubin did not affect the increase of other AIA-inducible hepatic enzymes. The succinyl-CoA synthetase [EC 6.2.1.4] activity in liver mitochondria was not influenced by administration of hemin or bilirubin.