Urinary clearance and metabolism of mevalonate by the isolataed perfused rat kidney.

Abstract

The urinary excretion and the incorporation into lipids of R[3-14C]mevalonate was investigated in isolated rat kidneys perfused with physiological concentration sof the substrate (80-500 pmol/ml). The clearance of R[3-14C]mevalonate and of the unnatural enantiomer S[5-14C]mevalonate were compared to the glomerular filtration ratea measured by the clearance of inulin. Evidence is presented that half of R-mevalonate filtered in the glomerulus is reabsorbed in the tubule whereas S-mevalonate is not reabsorbed. The kidney tubule appears to discriminate between the R and S forms of the mevalonate salt. Urinary excretion and incorporation into lipids accounted for 22% and 46%, respectively, of the uptake of R[3-14C]mevalonate from the perfusate. The label of R[3-14C]mevalonate recovered in lipids was distributed among saponifiable (15%), digitonin-precipitable sterols (18%) and squalene + prenols (67%). Sterol synthesis in the kidney appears to be controlled, at least in part, by the level of circulatinga R-mevalonate.