Role of the kidneys in the metabolism of circulating mevalonate in humans

M. Hughes-Fulford, K. R. Feingold, G. L. Searle, J. Wu, M. D. Siperstein, P. Y. Schoenfeld, G. Kaysen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Previous studies in several animal species have demonstrated that the kidneys are the primary site of mevalonate metabolism by the oxidative or shunt pathway. To determine the role of the human kidney in mevalonate oxidation, we studied mevalonate shunt activity in patients undergoing hemodialysis for varying degrees of renal failure. Surprisingly, at least half of the uremic patients and even anephric patients had normal ability to oxidize mevalonate by the shunt pathway. In addition, we found a strong negative correlation (R=-0.94) between mevalonate shunt activity and serum phosphorus levels in uremic patients. The resulting inhibition of mevalonate oxidation by high serum phosphorus levels was reversed by lowering the serum phosphorus in one patient. Finally, a positive correlation was found between mevalonate oxidation and serum PTH levels. The results of this study suggest that, in humans, extrarenal tissues can be major contributors to mevalonate oxidation. It is therefore probable that in humans, in contrast to other animals, the kidney is not the primary site of mevalonate metabolism by this oxidative pathway. Finally, the strong negative correlation between serum phosphorus levels and the ability of uremic patients to oxidize mevalonate suggests a regulatory role for the phosphate ion in the mevalonate shunt pathway.

Original languageEnglish (US)
Pages (from-to)1227-1231
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Volume62
Issue number6
StatePublished - 1986

Fingerprint

Mevalonic Acid
Metabolism
Kidney
Phosphorus
Oxidation
Serum
Animals
Renal Insufficiency
Renal Dialysis
Phosphates
Ions
Tissue

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Hughes-Fulford, M., Feingold, K. R., Searle, G. L., Wu, J., Siperstein, M. D., Schoenfeld, P. Y., & Kaysen, G. (1986). Role of the kidneys in the metabolism of circulating mevalonate in humans. Journal of Clinical Endocrinology and Metabolism, 62(6), 1227-1231.

Role of the kidneys in the metabolism of circulating mevalonate in humans. / Hughes-Fulford, M.; Feingold, K. R.; Searle, G. L.; Wu, J.; Siperstein, M. D.; Schoenfeld, P. Y.; Kaysen, G.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 62, No. 6, 1986, p. 1227-1231.

Research output: Contribution to journalArticle

Hughes-Fulford, M, Feingold, KR, Searle, GL, Wu, J, Siperstein, MD, Schoenfeld, PY & Kaysen, G 1986, 'Role of the kidneys in the metabolism of circulating mevalonate in humans', Journal of Clinical Endocrinology and Metabolism, vol. 62, no. 6, pp. 1227-1231.
Hughes-Fulford M, Feingold KR, Searle GL, Wu J, Siperstein MD, Schoenfeld PY et al. Role of the kidneys in the metabolism of circulating mevalonate in humans. Journal of Clinical Endocrinology and Metabolism. 1986;62(6):1227-1231.
Hughes-Fulford, M. ; Feingold, K. R. ; Searle, G. L. ; Wu, J. ; Siperstein, M. D. ; Schoenfeld, P. Y. ; Kaysen, G. / Role of the kidneys in the metabolism of circulating mevalonate in humans. In: Journal of Clinical Endocrinology and Metabolism. 1986 ; Vol. 62, No. 6. pp. 1227-1231.
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