On metabolic degradations of squalene, lanosterol and cholesterol in rat liver in vivo. Evidence for recycling of metabolites for the synthesis of isoprene compounds.

Abstract

Abstract(1) Radioactivity of biosynthetically labeled squalene, injected in tracer amounts in rats is incorporated to about equal parts into cholesterol and component(s) of the fatty acid fraction of the liver. The ubiquinones isolated from the liver are radioactive and show about the same specific radioactivity as the cholesterol. It appears therefore, that the squalene which escapes incorporation into cholesterol is degraded to metabolite(s) suited for the synthesis of isoprene compounds.(2) Radioactivity of injected biosynthetically and chemically labeled cholesterol is traced in the ubiquinones and the squalene of rat liver indicating that a degradation of cholesterol and a recycling of the metabolite(s) occurs.(3) A recycling of metabolite(s) of squalene and of cholesterol can explain the observation that after labeled mevalonate or acetate as precursor, radioactivity can be traced in the squalene of the liver many hours after the injection and maintains a constant value during a period of several hours.(4) Radioactivity of biosynthetically labeled lanosterol is not only incorporated into cholesterol but a considerable part of it into component(s) of the bile acid fraction of the liver. Evidence is obtained that this transformation occurs by circumventing cholesterol as intermediate.