Mechanism of allylisopropylacetamide-induced increase of δ-aminolevulinate synthetase in liver mitochondria: IV. Accumulation of the enzyme in the soluble fraction of rat liver

Abstract

When the synthesis of hepatic ALA synthetase was induced in rats by the administration of allylisopropylacetamide, high activities of ALA synthetase accumulated not only in the mitochondrial fraction but also in the soluble fraction. Cycloheximide inhibited the synthesis of both ALA synthetases in mitochondrial and extramito-chondrial fractions, while the enzyme synthesis was not affected by chloramphenicol. The induction of ALA synthetase in either fraction was also suppressed by the administration of mitomycin C, actinomycin D, hemin, or bilirubin. The apparent halflife time of ALA synthetase in the soluble fraction was approximately 20 min, while that of the mitochondrial enzyme was about 68 min. Furthermore, a definite difference between these two enzymes was observed on fractionation by ammonium sulfate. The possibility was suggested that ALA synthetase is synthesized originally in the microsomal system and subsequently is transferred into mitochondria and settles there, and the enzyme is probably modified to some extent before or after entering the mitochondria.