The level of 7-dehydrocholesterol in plasma reflects the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase in the human liver

Abstract

Plasma levels of the cholesterol precursor 7-dehydrocholesterol (7-DHC) were compared with activities of the rate-limiting enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase assayed in liver biopsies from patients undergoing cholecystectomy. Some patients were treated with cholestyramine, deoxycholic acid or chenodeoxycholic acid prior to surgery in order to alter the activity of the enzyme. The median level of 7-DHC and the activity of HMG-CoA reductase in the untreated group were 55 ng/ml and 98 pmol/min/mg protein, respectively. The sterol levels and enzyme activities were increased in patients treated with cholestyramine (85 ng/ml and 439 pmol/min/mg protein) and deoxycholic acid (86 ng/ml and 173 pmol/min/mg protein) and decreased in patients treated with chenodeoxycholic acid (38 ng/ml and 51 pmol/min/mg protein). There was a strong positive correlation (r_s=0.75, P<0.0005) between the plasma levels of 7-DHC and the activities of hepatic HMG-CoA reductase in these patients. This correlation was further improved when the plasma levels of 7-DHC were expressed relative to those of cholesterol (r_s=0.90, P<0.0001). The results show that the level of 7-DHC in plasma reflects the activity of HMG-CoA reductase in the liver.