Effects of Hemin on the Synthesis and Intracellular Translocation of δ-Aminolevulinate Synthase in the Liver of Rats Treated with 3, 5-Dicarbethoxy-1,4-Dihydrocollidine1

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Abstract
The administration of hemin to rats which had been treated with 3,5-dicarbethoxy-1,4-dihy-drocollidine (DDC) brought about a rapid decrease of the δ-aminolevulinate (ALA) synthase activity in the mitochondria and an appreciable increase of the enzyme activity in the cytosol in the liver. In DDC-treated rats, however, the degree of accumulation of ALA synthase in the liver cytosol resulting from the hemin administration was relatively small and the total ALA synthase activity in the liver was considerably decreased after the hemin administration; these results are in contrast with those for allylisopropylacetamide-treated rats. Further studies by combined use of [3H]leucine and an anti-ALA synthase IgG revealed that incorporation of [3H]leucine into the mitochondrial ALA synthase was greatly reduced in hemin injected rats and that incorporation of [3H]leucine into total ALA synthase in the liver (the sum of radioactivity incorporated into the mitochondrial enzyme and the cytosolic enzyme) was also decreased to a considerable extent in these rats; this decrease in incorporation of [3H]leucine appeared to occur immediately after the administration of hemin. It was concluded that hemin actually inhibits the translocation of ALA synthase from the cytosol into the mitochondria and that hemin also inhibits de novo synthesis of ALA synthase, possibly at a post-transcriptional level in DDC-treated rats.