The role of kidneys in mevalonate metabolism: fact and artifact

This laboratory has previously demonstrated that circulating mevalonate is metabolized primarily by the kidneys by both the sterol and nonsterol pathways of mevalonate metabolism. Bardenheier and Popják recently challenged this conclusion, claiming that a contaminant in commercially obtained 5-¹⁴C]mevalonate can artifactually account for much of the ¹⁴C reported as ¹⁴CO₂ in such experiments.In the present study, this contaminant was shown to occur at levels averaging only 0.08% and even if not corrected for, would cause less than a 4% error in calculating renal mevalonate oxidation. Further, regardless of the minor degree of contamination of commercial ¹⁴C-mevalonate, the kidney oxidized mevalonate to CO₂ at rates averaging 24 times that of the liver. Finally, purified (R)-5-¹⁴C]mevalonate was shown to yield results virtually identical, both in vitro and in vivo, to those obtained with commercial 5-¹⁴C]mevalonate. These data, therefore, fully confirm our previous conclusion that the kidney represents the primary organ site of mevalonate metabolism by the nonsterol, or shunt, pathway.