Abstract

The activity of mevalonate kinase and of mevalonate pyrophosphate decarboxylase in human skin fibroblasts grown in culture was increased when whole fetal calf serum in the incubation medium was replaced with lipid-deficient serum. The drug demecolcine interfered with low density lipoprotein binding by cells and increased sterol synthesis and activities of hydroxymethylglutaryl-CoA reductase and mevalonate kinase. In contrast to normal cells, fibroblasts from a patient with homozygous familial hypercholesterolemia did not show any lower mevalonate kinase activity following incubation with whole serum compared with that in cells incubated with lipid-deficient serum. Insulin increased the activity of mevalonate kinase in fibroblasts. Livers of rats fed for 7 days with a diet containing 1% cholesterol showed reduced activity of mevalonate kinase and mevalonate phosphate kinase. These results are consistent with the possibility that enzymatic reactions other than those catalyzed by hydroxymethylglutaryl-CoA reductase may play a role in the physiological regulation of sterol synthesis in mammalian tissues.