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American Journal of Clinical Nutrition, Vol 10, 310-322, Copyright © 1962 by The American Society for Clinical Nutrition, Inc.

Inhibitors of Cholesterol Biosynthesis which Act at or Beyond the Mevalonic Acid Stage

WILLIAM L. HOLMES PH.D.1 and NICHOLAS W. DITULLIO M.S.1

1 From the Research and Development Division, Smith Kline & French Laboratories, Philadelphia, Pennsylvania

Evidence has been obtained which suggests that the hypocholesterolemic agent, SK&F 7732 and its diethyl analog, SK&F 7997, inhibit cholesterol synthesis in vitro at a site lying between lanosterol and zymosterol on the biosynthetic pathway. Comparative studies in vitro and in vivo concerning the sites at which SK&F 525, SK&F 3301, triparanol and benzmalacene inhibit cholesterol synthesis have been reported. All these agents, with the exception of the latter, were found to inhibit the biosynthetic pathway at more than one site both in vivo and in vitro. In addition, some correlation was found between the activity in vitro and in vivo. Gas chromatographic analysis of tissues from pretreated animals revealed that only triparanol caused an accumulation of a sterol other than cholesterol. Studies with other classes of inhibitors which block cholesterol synthesis beyond the mevalonic acid stage have been reviewed.




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A. J. Merola and A. Arnold
Estrone Inhibition of Cholesterol Biosynthesis at the Mevalonic Acid Stage
Science, April 17, 1964; 144(3616): 301 - 302.
[Abstract] [PDF]


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Copyright © 1962 by The American Society for Nutrition