Abstract
Summary
The effects of the hypocholesterolemic agents, trans-1,4-bis- (2-chloro-benzylaminomethyl) -cyclohexane dihy dro-chloride (AY9944) and beta-benzalbutyric acid (BBB), on the level (activity) of delta-aminolevulinic acid synthetase (ALAS) in the mitochondria of livers of mice injected with certain porphyrinogenic compounds were studied. The porphyrinogenic agents employed were allylisopropylacetamide (AIA) and 3,5-dicarbethoxy-1,4-dihydro-2,4,6-trimethylpyridine (DDC). All substances were administered parenterally.
Both AY-9944 and BBB injections prevented the increase in hepatic mitochondrial ALA-synthetase levels which otherwise follow the injection of AIA or DDC. AY-9944 administration also produced a consistent decrease in serum cholesterol levels. These data suggest that a decrease in the hepatic steroid “pool” and presumably that of 5-beta-H-steroid metabolites, as reflected by the serum cholesterol level, is associated with the observed decrease in hepatic mitochondrial ALAS.
The present data thus support, by an entirely different approach, other evidence implicating steroid metabolites in the regulation of porphyrin-heme biosynthesis in a mammalian species.
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