Synthesis of delta 2-isopentenyl tRNA from mevalonate in cultured human fibroblasts.
Human fibroblasts are shown to incorporate [3H]-mevalonolactone into 3H-labeled delta 2-isopentenyl tRNA. This incorporation was observed in cells that were incubated with compactin (ML-236B), an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme. A reductase that blocks mevalonate production by cells. When incubated with low concentrations of [3H]mevalonolactone in the presence of compactin and in the absence of exogenous cholesterol, the cells incorporated small amounts of [3H]mevalonolactone into delta 2-isopentenyl tRNA and large amounts into cholesterol. In the presence of low density lipoprotein, which serves as a source of cholesterol, the incorporation of [3H]mevalonolactone into cholesterol was reduced by 90% and the incorporation into delta 2-isopentenyl tRNA was stimulated by 10-fold. Thus, cultured mammalian cells are now known to use mevalonate for synthesis of three nonsterol products, ubiquinone, dolichol, and delta 2-isopentenyl tRNA, as well as for synthesis of cholesterol.
D000475:Alkenes / Q000096:biosynthesis*; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008798:Mevalonic Acid / Q000378:metabolism*; D012343:RNA, Transfer / Q000096:biosynthesis*; D014316:Tritium; D014451:Ubiquinone / Q000096:biosynthesis
C025669:2-isopentenyl tRNA; D000475:Alkenes; D008077:Lipoproteins, LDL; D014316:Tritium; D014451:Ubiquinone; D012343:RNA, Transfer; D002784:Cholesterol; D008798:Mevalonic Acid