Abstract
The demethylation of puromycin and related compounds by rat liver microsomal enzymes has been demonstrated. The reaction is localized in the liver and requires microsomes, oxygen and NADPH. Magnesium is not necessary. Rat, mouse and guinea-pig demethylated puromycin and related compounds to different degrees. Demethylation of puromycin and related compounds was inhibited by diethylaminoethyldiphenylpropyl acetate (SKF-525-A), the aminonucleoside of puromycin being the most sensitive. There were marked differences in the extent of demethylation of a series of puromycin analogs and related compounds. However, no correlation could be found between the lipid solubility of these compounds and their extent of metabolism. Pretreatment of rats with phenobarbital markedly stimulated the demethylation of puromycin and related compounds.
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