The effects of phosphate on the biosynthesis of cholesterol in rat liver homogenates.

The biosyntheses of cholesterol from acetate and mevalonate were determined in rat liver homogenates that were prepared and incubated in buffers containing varying concentrations of phosphate. Relatively little acetate or mevalonate was incorporated into cholesterol in the absence of added phosphate. When phosphate was added, there was an increase in incorporation of both substrates. The addition of phosphate resulted in an increase in the incorporation of mevalonate to a maximum, whereas phosphate appeared to increase the incorporation of acetate at low phosphate levels and decrease the incorporation at higher phosphate levels. The results appear to be consistent with the possibility that, at low phosphate levels, the biosynthesis of cholesterol is limited by some phosphate-requiring reaction(s) in the pathway after mevalonate, and at higher phosphate levels, the biosynthesis is limited by the 3-hydroxy-3-methylglutaryl coenzyme A reductase-catalyzed step.