Urinary clearance and metabolism of mevalonate by the isolataed perfused rat kidney
Brunengraber, H.; Weinstock, S.B.; Story, D.L.; Kopito, R.R.
Journal of Lipid Research 22(6): 916-920
ISSN/ISBN: 0022-2275 PMID: 7276751 Accession: 006873035
The urinary excretion and the incorporation into lipids of R[3-14C]mevalonate were investigated in isolated rat kidneys perfused with physiological concentrations of the substrate (80-500 pmol/ml). The clearances of R[3-14C]mevalonate and of the unnatural enantiomer S[5-14C]mevalonate were compared to the glomerular filtration rate measured by the clearance of inulin. Evidence is presented that 1/2 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 partly by the level of circulating R-mevalonate.