THE LEVEL OF 7-DEHYDROCHOLESTEROL IN PLASMA REFLECTS THE ACTIVITY OF 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE IN THE HUMAN LIVER

Plasma levels of the cholesterol precursor 7-dehydrocholesterol (7-DHC ) were compared with activities of the rate-limiting enzyme in cholest erol biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) red uctase assayed in liver biopsies from patients undergoing cholecystect omy. Some patients were treated with cholestyramine, deoxycholic acid or chenodeoxycholic acid prior to surgery in order to alter the activi ty of the enzyme. The median level of 7-DHC and the activity of HMG-Co A reductase in the untreated group were 55 ng/ml and 98 pmol/min/mg pr otein, respectively. The sterol levels and enzyme activities were incr eased in patients treated with cholestyramine (85 ng/ml and 439 pmol/m in/mg protein) and deoxycholic acid (86 ng/ml and 173 pmol/min/mg prot ein) and decreased in patients treated with chenodeoxycholic acid (38 ng/ml and 51 pmol/min/mg protein). There was a strong positive correla tion (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 co rrelation was further improved when the plasma levels of 7-DHC were ex pressed relative to those of cholesterol (r(s) = 0.90, P < 0.0001). Th e results show that the level of 7-DHC in plasma reflects the activity of HMG-CoA reductase in the liver. (C) 1998 Published by Elsevier Sci ence B.V. All rights reserved.