Inhibition of hepatic cholesterol synthesis in mice by sterols with shortened and stereochemically varied side chains.

AUTOR(ES)

Erickson, K A

RESUMO

Mice were fed cholesterol or various other sterols for 26 hr, after which the amount of hepatic cholesterol synthesis was measured in a cell-free system. The following sterols were as effective as cholesterol itself in depressing the conversion of acetate into sterol: pregn-5-en-3 beta-ol, which lacks an isohexyl group on C-20; (E)-17(20)-dehydrocholesterol, in which the isohexyl group is fixed to the right; (E)-20(22)-dehydrocholesterol, in which C-23 is oriented away from the nucleus; and 20-epicholesterol. Moreover, when the isohexyl group was fixed to the left in (Z)-17(20)-dehydrocholesterol, this dietary sterol, identified in the liver, caused not only a depression in the conversion of both mevalonate and squalene into sterols. The incorporation of acetate into fatty acids was not depressed, nor did the (Z)-sterol appear to have a generalized effect on membranous enzymes, because the activity of glucose-6-phosphatase was unaffected. Thus, feedback inhibition was retained when the stereochemistry of cholesterol's side chain was drastically changed and even after the nearly complete removal of the side chain. This implies that the side chain is only minimally recognized by the mechanisms involved in feedback inhibition.

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