Suppression of hepatic cholesterogenesis in the rat by lithium ion

Abstract

The effects of lithium ion on the rates of incorporation of acetate-1-14C and mevalonic-2-14C acid into cholesterol, on 14CO2 production and acetoacetate formation from carboxyl-labeled acetate, on serum and liver cholesterol levels, and on the acetate-activating system were studied in rat liver.It has been found that while the incorporation of labeled acetate into cholesterol was strongly suppressed by lithium ion, incorporation of mevalonate into cholesterol under the same conditions was virtually unchanged. It thus appears that lithium ion produces its effect prior to the formation of mevalonic acid in the pathway of cholesterol biosynthesis.Liver cholesterol levels are practically unchanged after 4 weeks' treatment with lithium chloride while serum cholesterol, under the same conditions, appears to be slightly increased in the treated animals. 14CO2 production and acetoacetate formation from carboxyl-labeled acetate, and the acetate-activating system of rat liver appear to be slightly impaired by lithium ion. The possibility of the existence of more than one block between acetate and mevalonic acid on the cholesterol biosynthetic pathway is discussed.