Abstract
The mechanism by which chlorpromazine inhibits cholesterogenesis in rat liver was investigated in vitro with the use of [14C] acetate and [14C] mevalonate as sterol precursors. Evidence was obtained that chlopromazine blocks cholesterogenesis at multiple sites beyond HMGCoA reductase (β-hydroxy-β-methylglutarylCoA reductase, EC 1.1.1.34), the rate-limiting step. Squalene synthesis from both labeled acetate and mevalonate is reduced to a similar extent in the presence of chlorpromazine (29–36% at 0.5 mM). The data indicate that there is also an impairment of conversion of squalene to lanosterol, and of lanosterol to cholesterol. Overall inhibition of cholesterogenesis by chlorpromazine reached 65–75% at 0.5 mM and was concentration-dependent over the range 0.15–1.0 mM.
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Bell, F.P., Hubert, E.V. Evidence that chlorpromazine inhibits sterologenesis at post-HMGCoA reductase sites in rat liver, in vitro. Lipids 18, 668–671 (1983). https://doi.org/10.1007/BF02534681
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DOI: https://doi.org/10.1007/BF02534681