CHOLESTA-5,7,9(11)-TRIEN-3-BETA-OL FOUND IN PLASMA OF PATIENTS WITH SMITH-LEMLI-OPITZ-SYNDROME INDICATES FORMATION OF STEROL HYDROPEROXIDE

The Smith-Lemli-Opitz syndrome (SLOS) is an autosomal recessive disord er characterized by accumulation of cholesta-5, 7-dien-3 beta-ol cause d hy a deficience of the enzyme desaturating this sterol to chorestero l. In addition to other unusual sterols recently found in plasma of pa tients with SLOS, namely cholesta-5, 8-Dien-3 beta-ol and 19-nor-chole sta-5,7,9(10)-trien-3 beta-ol we have detected a trienol and we descri be here its identification as cholesta-5,7,9(11)-trien-3 beta-ol by GC -MS and by comparison with a synthetic standard. We tested the possibi lity that the trienoI may be formed by radical oxidation of cholesta-5 ,7-dien-3 beta-ol accumulated in plasma of patients with SLOS because it is known to be formed by decomposition of 7-hydroperoxy-cholesta-5, 8-dien-3 beta-ol, which is a product of cholesta-5,7-dien-3 beta-ol ph otooxidation. Incubation of cholesta-5,7-dien-3 beta-ol with rat liver microsomes in the presence of ADP/Fe2+ and NADPH gave rise to a numbe r of oxygenated sterols. Among these, analysis by particle-beam LC-MS under CI conditions indicated the presence of 7-hydroperosy-cholesta-5 ,8-dien-3 beta-ol and of cholesta-5,7,9(11)trien-3 beta-ol which is kn own to derive from the oxidation of the 7-hydroperoxide. From these re sults we conclude that cholesta-5,7-dien-3 beta-ol accumulated in tiss ues of patients with SLOS may be oxidized by oxygen radicals giving ri se to oxygenerated sterols. Some of these compounds may be toxic and m ay contribute to worsen the pathological picture in patients with SLOS .-De Fabiani, E., D. Caruso, M. Cavaleri, M. Galli Kienle, and G. Gall i. Cholesta-5,7,9(11)-trien-3 beta-ol found in plasma of patients with Smith-Lemli-Opitz syndrome indicates formation of sterol hydroperoxid e.