Evidence for the transcriptional inhibition by heme of the synthesis of δ-aminolevulinate synthase in rat liver

Intravenous administration of various doses of hemin to allylisopropylacetamide-pretreated rats resulted in a dose-dependent and time-dependent decrease of the ability of liver polysomes to direct the synthesis of δ-aminolevulinate synthase in vitro in a reticulocyte lysate system. The apparent half-time of decrease of the ability of polysomes observed at a maximal dose of hemin was about 60 min; this value is comparable to the previously estimated half-life of δ-aminolevulinate synthase mRNA. It was assumed that heme inhibits the synthesis of δ-aminolevulinate synthase also at a transcriptional step. δ-Aminolevulinate synthase synthesized in vitro had a minimum molecular weight of about 75,000, whereas the value for the liver mitochondrial δ-aminolevulinate synthase was about 66,000.