THE METABOLISM OF DESMOSTEROL IN HUMAN SUBJECTS DURING TRIPARANOL ADMINISTRATION*

Abstract

Conversion of 24-dehydrocholesterol (desmosterol) to bile acids and steroid hormones during triparanol administration was studied in two male subjects. In each, DL-2-C14-mevalonic acid was injected (IV) intravenously and C14-specific radioactivity of serum desmosterol (DM) and cholesterol (CL) determined after 3 hours and at 1 to 3 day intervals thereafter. Radioactivity rapidly appeared in DM; CL C14-specific activity was very much lower during the first few days of each study. Bile was collected by duodenal intubation and bile acids extracted and purified by column chromatography. Urinary metabolites of cortisol were extracted from 24 hour urine sample and purified by chromatography. In one study, derivatives of urinary C19O2 steroids were separately isolated and purified. In both patients the C14-specific activity of the bile acids and steroids was much higher than that of CL throughout the study, demonstrating that a significant part of these compounds must have been made directly from DM. The specific activity data and other considerations suggest that DM is similar to CL in its ability to serve as a direct precursor for several sterol metabolites, namely bile acids and steroid hormones. In one study, 7-[alpha]-H3-CL, incorporated in the patient''s serum lipoproteins, was injected with the C14-mevalonate. Comparison of the serum specific activity curves for the two sterols (C14-DM and H3-CL) showed that their disappearance rates were similar, DM disappearance being a little more rapid than that of CL. Calculation of the overall metabolism of DM from the double-isotope data showed that only 21 [plus or minus] 4% of the DM that disappeared from the metabolically active pool reappeared therein as CL.