Actinomycin D-induced enhancement of ubiquinone biosynthesis in rat.
Administration of actinomycin D to fasted rats induces an enhancement of the labeling of hepatic ubiquinone by [2-14C] acetate both in vivo and in vitro. The incorporation of [2-14C] mevalonate into ubiquinone is also increased, although to a significantly lesser extent; this, however, presumably results from greater uptake of the labeled precursor by liver of drug-treated rats. The drug-administered animals show increased activity of liver microsomal mevalonate: NADP oxidoreductase, the rate-limiting enzyme in isoprenoid biogenesis. The incorporation of [u-14C] benzoic acid and CH3-[14C] methionine into ubiquinone in liver slices, however, reveals a decrease in actinomycin D administered rats. This appears to be due to a specific inhibition of the pathway leading to the benzoquinone moiety of ubiquinone and not to an increase in the pool-size of the precursors. The stimulatory effect of the drug on ubiquinone biosynthesis is also observable in cholesterol-fed rats. The actinomycin D-induced increase in ubiquinone biosynthesis is dependent on new protein synthesis since the effect is abolished by treating the animals with either cycloheximide or puromycin.
D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active; D002784:Cholesterol / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism; D011691:Puromycin / Q000494:pharmacology; D051381:Rats; D014451:Ubiquinone / Q000096:biosynthesis*
D000596:Amino Acids; D014451:Ubiquinone; D003609:Dactinomycin; D011691:Puromycin; D002784:Cholesterol; D003513:Cycloheximide; D000429:Alcohol Oxidoreductases; D008798:Mevalonic Acid