title: Inhibition of acyl CoA: cholesterol acyltransferase and sterologenesis in rat liver by diazepam, in vitro.
abstract: Diazepam, a commonly prescribed tranquilizer, was found to inhibit cholesterol biosynthesis in rat liver minces; inhibition appeared to occur at multiple post-mevalonate sites. Diazepam also inhibited cholesterol esterification by acylCoA:cholesterol acyltransferase in isolated liver microsomes and minces. Liver minces incubated with [14C]oleate demonstrated increased uptake of the fatty acid and a greater incorporation of the substrate into triglycerides, diglycerides and phospholipids when diazepam was present. The results suggest possible mechanisms for the hypocholesterolemic effect of diazepam in experimental animals and for the elevation of triglycerides and very low-density lipoproteins in man and the rat.
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis; D002788:Cholesterol Esters / Q000096:biosynthesis; D003975:Diazepam / Q000494:pharmacology*; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*; D013261:Sterols / Q000096:biosynthesis*
chemical_list: D002788:Cholesterol Esters; D013261:Sterols; D002784:Cholesterol; D002785:Sterol O-Acyltransferase; D003975:Diazepam