Abstract
2, 3-Iminosqualene (ISq) is a powerful inhibitor of squalene oxide: lanosterol cyclase (EC 5.4.99.7). When added to lipid-depleted culture media (LDM) of rat hepatoma (H-4-II-E-C3) or Chinese hamster ovary (CHO) cells at a concentration of 10 μg ml
-1
, it causes the cells to float off the substratum in a few days. Lipoproteins in the culture medium completely counteract this effect. Cells in lipoprotein-containing media (FGM) grow normally in the presence of ISq. Irrespective of the culture medium, ISq at 10 μg ml
-1
causes an almost complete and apparently irreversible inactivation of the squalene oxide cyclase in CHO and H4 cells and the accumulation in the cells of squalene, of squalene 2, 3-oxide (mostly), and of squalene 2, 3-22, 23-dioxide when [
14
C]acetate or [
14
C]mevalonate is fed to the cells. Chronic treatment of H4 cells with ISq failed to elicit induction of the cyclase, but increased the conversion of mevalonate into squalene and squalene dioxide, and depressed the conversion of squalene oxide to the dioxide. Cells loaded with squalene and the squalene oxides from mevalonate in the presence of ISq get rid of these substances by rapidly secreting them into the media and by some unidentified metabolic processes.
Reference11 articles.
1. A Direct Synthesis of 2,3-Epiminosqualene
2. Induction of 3- hydroxy-3-methylglutaryl coenzyme A reductase activity in human fibroblasts incubated with compactin (ML-236B), a competitive inhibitor of the reductase. biol;Brown M. S.;Chem.,1978
3. Multivalent regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth;Brown M. S.;Lipid Res.,1980
4. Inhibition of cholesterol biosynthesis in Chinese hamster ovary cells by 4,4,10-trimethyl;Chang T. Y.;J. Biol. Chem.,1979
5. 2,3-Iminosqualene, a potent inhibitor of the enzymic cyclization of 2,3-oxidosqualene to sterols. Am. chem;Corey E. J.;Soc.,1967
Cited by
13 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献