Metabolism of mevalonate in rats and man not leading to sterols

Abstract

C-5 of mevalonate appears as C0-2 in the breath of rats and men almost immediately after administration either by injection or by mouth. Adult rats exhaled up to 6.5% of a dose of RS-[5-14C]mevalonate (13% of the utilizable R-enantiomer) in the breath in 100 min. The 14-C02 was not derived either from the matabolism of cholesterol biosynthesized from [5-14C]mevalonate or from the metabolism of the unnatural S-enantiomer of mevalonate. The amount of 14-C02 expired in the breath was the same whether the [5-14C]mevalonate was given intravenously or in a drink of water to man. One normocholesterolemic man dissipated 12%, a mildly non-familial hypercholesterolemic man dissipated 10%, and a familial hypercholesterolemic man dissipated 7% of a dose of [5-14C]mevalonate in 24 hours (calculated as a per cent of the R-enantiomer). The observations support the hypothesis of the existence of a metabolic shunt of intermediates of sterol biosynthesis, derived from mevalonate, not leading to sterols.