The Biochemistry of Animal Cells

IV. Biosynthesis of Cholesterol and Its Regulation in Dispersed Rat Liver Cells

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Rat liver dispersed cells showed activities to synthesize cholesterol as well as lipid by means of 1-C¹⁴-acetate incorporation, when they were fortified with various cofactors, such as Mn⁺⁺, Mg⁺⁺, NADPH, ATP, GSH and citrate. The stimulatory effect of citrate on cholesterol synthesis was about half of that on lipid synthesis. Malonyl-CoA was found to be a better precursor of cholesterol than acetate. The dispersed liver cells isolated from diabetic rats showed no impairment of cholesterol synthesis, whereas lipid synthesis was depressed to one third of normal. From these results, it was suggested that malonyl-CoA may be a physiological intermediate for cholesterol synthesis, as well as lipid forma-tion, but condensation of two moles of acetyl-CoA may become an important shunt when formation of malonyl-CoA is disturbed, as in the diabetic state.
Insulin stimulated cholesterol formation as well as lipid synthesis only when added with pyruvate. In contrast to its inhibitory effect on lipid synthesis, epinephrine also stimulated cholesterol synthesis. The me-chanism regulating cholesterol formation was discussed in connection with lipid synthesis.