Post-HMG CoA reductase regulation of cholesterol biosynthesis in normal human lymphocytes: Lanosten-3β-ol-32-al, a natural inhibitor

Abstract

Normal human lymphocytes stimulated by culture in a lipid-depleted medium were used to study the post-HMG CoA regulations of cholesterol biosynthesis. A thorough analysis of the non-saponifiable material obtained after incorporation of [ 14C]-mevalonic acid permitted localization of the main regulatory steps at mevalonic acid degradation (according to the Edmond and Popjak' shunt pathway) and lanosterol demethylation. The last process was blocked essentially at the deformylation of lanosten-3β-ol-32-al, an intermediate which accumulates in the cell. This intermediate which was isolated and identified, has inhibitory properties towards HMG CoA reductase and thus could be considered as an endogenous cellular bioregulator of cholesterol biosynthesis.