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Chemical Compound Review

DL-Mevalonate     3,5-dihydroxy-3-methyl- pentanoic acid

Synonyms: RS-Mevalonate, Hiochic acid, CHEBI:25351, HMDB00227, HSDB 7681, ...
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Disease relevance of mevalonic acid


Psychiatry related information on mevalonic acid

  • The results indicate that Alzheimer's disease results in specific and significant changes in the levels of lipid products of the mevalonate pathway in the brain [6].

High impact information on mevalonic acid

  • The activity of mevalonate kinase, the enzyme that catalyzes the first step in mevalonate metabolism, was severely deficient in the patient's fibroblasts, lymphocytes, and lymphoblasts [7].
  • In the subsequent pregnancy of the patient's mother, gas chromatography-mass spectrometry demonstrated a marked elevation of mevalonic acid in the mother's urine and a 3000-fold elevation, as compared with control levels in the amniotic fluid, suggesting that the fetus was affected [7].
  • Furthermore, drugs that inhibit mevalonate biosynthesis blocked the in vivo action of oncogenic derivatives of human Ras protein in the Xenopus oocyte assay [8].
  • Thus, the mevalonate requirement for Ras activation may indicate that attachment of a mevalonate-derived (isoprenoid) moiety to Ras proteins is necessary for membrane association and biological function [8].
  • 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase is a critical enzyme in the mevalonate pathway that regulates the biosynthesis of cholesterol as well as isoprenoids that mediate the membrane association of certain GTPases [9].

Chemical compound and disease context of mevalonic acid


Biological context of mevalonic acid


Anatomical context of mevalonic acid


Associations of mevalonic acid with other chemical compounds


Gene context of mevalonic acid


Analytical, diagnostic and therapeutic context of mevalonic acid


  1. Statin-induced inhibition of the Rho-signaling pathway activates PPARalpha and induces HDL apoA-I. Martin, G., Duez, H., Blanquart, C., Berezowski, V., Poulain, P., Fruchart, J.C., Najib-Fruchart, J., Glineur, C., Staels, B. J. Clin. Invest. (2001) [Pubmed]
  2. Mevalonate availability affects human and rat resistance vessel function. Roullet, J.B., Xue, H., Roullet, C.M., Fletcher, W.S., Cipolla, M.J., Harker, C.T., McCarron, D.A. J. Clin. Invest. (1995) [Pubmed]
  3. Lovastatin and phenylacetate inhibit the induction of nitric oxide synthase and cytokines in rat primary astrocytes, microglia, and macrophages. Pahan, K., Sheikh, F.G., Namboodiri, A.M., Singh, I. J. Clin. Invest. (1997) [Pubmed]
  4. Inhibition of pancreatic adenocarcinoma cell growth by lovastatin. Sumi, S., Beauchamp, R.D., Townsend, C.M., Uchida, T., Murakami, M., Rajaraman, S., Ishizuka, J., Thompson, J.C. Gastroenterology (1992) [Pubmed]
  5. Engineering a mevalonate pathway in Escherichia coli for production of terpenoids. Martin, V.J., Pitera, D.J., Withers, S.T., Newman, J.D., Keasling, J.D. Nat. Biotechnol. (2003) [Pubmed]
  6. Ubiquinone, dolichol, and cholesterol metabolism in aging and Alzheimer's disease. Edlund, C., Söderberg, M., Kristensson, K., Dallner, G. Biochem. Cell Biol. (1992) [Pubmed]
  7. Mevalonic aciduria--an inborn error of cholesterol and nonsterol isoprene biosynthesis. Hoffmann, G., Gibson, K.M., Brandt, I.K., Bader, P.I., Wappner, R.S., Sweetman, L. N. Engl. J. Med. (1986) [Pubmed]
  8. Genetic and pharmacological suppression of oncogenic mutations in ras genes of yeast and humans. Schafer, W.R., Kim, R., Sterne, R., Thorner, J., Kim, S.H., Rine, J. Science (1989) [Pubmed]
  9. Isoprenoids determine Th1/Th2 fate in pathogenic T cells, providing a mechanism of modulation of autoimmunity by atorvastatin. Dunn, S.E., Youssef, S., Goldstein, M.J., Prod'homme, T., Weber, M.S., Zamvil, S.S., Steinman, L. J. Exp. Med. (2006) [Pubmed]
  10. Cloning and characterization of a gene from Escherichia coli encoding a transketolase-like enzyme that catalyzes the synthesis of D-1-deoxyxylulose 5-phosphate, a common precursor for isoprenoid, thiamin, and pyridoxol biosynthesis. Lois, L.M., Campos, N., Putra, S.R., Danielsen, K., Rohmer, M., Boronat, A. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  11. Alendronate mechanism of action: geranylgeraniol, an intermediate in the mevalonate pathway, prevents inhibition of osteoclast formation, bone resorption, and kinase activation in vitro. Fisher, J.E., Rogers, M.J., Halasy, J.M., Luckman, S.P., Hughes, D.E., Masarachia, P.J., Wesolowski, G., Russell, R.G., Rodan, G.A., Reszka, A.A. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  12. Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in Morris hepatoma 7800 after intravenous injection of mevalonic acid. George, R., Goldfarb, S. Cancer Res. (1980) [Pubmed]
  13. Alendronate inhibits invasion of PC-3 prostate cancer cells by affecting the mevalonate pathway. Virtanen, S.S., Väänänen, H.K., Härkönen, P.L., Lakkakorpi, P.T. Cancer Res. (2002) [Pubmed]
  14. Lovastatin inhibits proliferation of rat mesangial cells. O'Donnell, M.P., Kasiske, B.L., Kim, Y., Atluru, D., Keane, W.F. J. Clin. Invest. (1993) [Pubmed]
  15. Sex difference in human mevalonate metabolism. Feingold, K.R., Wiley, M.H., Searle, G.L., Machida, B.K., Siperstein, M.D. J. Clin. Invest. (1980) [Pubmed]
  16. Human T cell receptor gammadelta cells recognize endogenous mevalonate metabolites in tumor cells. Gober, H.J., Kistowska, M., Angman, L., Jenö, P., Mori, L., De Libero, G. J. Exp. Med. (2003) [Pubmed]
  17. Isoprenoid metabolism is required for stimulation of the respiratory burst oxidase of HL-60 cells. Bokoch, G.M., Prossnitz, V. J. Clin. Invest. (1992) [Pubmed]
  18. 3-Hydroxy-3-methylglutaryl coenzyme A reductase in anencephalic and normal human fetal liver. Carr, B.R., Rainey, W.E., Mason, J.I. J. Clin. Invest. (1985) [Pubmed]
  19. In vivo requirement of protein prenylation for maintenance of retinal cytoarchitecture and photoreceptor structure. Pittler, S.J., Fliesler, S.J., Fisher, P.L., Keller, P.K., Rapp, L.M. J. Cell Biol. (1995) [Pubmed]
  20. Influence of thyroid hormone status on mevalonate metabolism in rats. Feingold, K.R., Wiley, M.H., MacRae, G., Siperstein, M.D. J. Clin. Invest. (1980) [Pubmed]
  21. Regulated degradation of HMG-CoA reductase, an integral membrane protein of the endoplasmic reticulum, in yeast. Hampton, R.Y., Rine, J. J. Cell Biol. (1994) [Pubmed]
  22. Distinct light-mediated pathways regulate the biosynthesis and exchange of isoprenoid precursors during Arabidopsis seedling development. Rodríguez-Concepción, M., Forés, O., Martinez-García, J.F., González, V., Phillips, M.A., Ferrer, A., Boronat, A. Plant Cell (2004) [Pubmed]
  23. Structural genomics of enzymes involved in sterol/isoprenoid biosynthesis. Bonanno, J.B., Edo, C., Eswar, N., Pieper, U., Romanowski, M.J., Ilyin, V., Gerchman, S.E., Kycia, H., Studier, F.W., Sali, A., Burley, S.K. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  24. Brain cholesterol turnover required for geranylgeraniol production and learning in mice. Kotti, T.J., Ramirez, D.M., Pfeiffer, B.E., Huber, K.M., Russell, D.W. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  25. Arabidopsis thaliana contains two differentially expressed 3-hydroxy-3-methylglutaryl-CoA reductase genes, which encode microsomal forms of the enzyme. Enjuto, M., Balcells, L., Campos, N., Caelles, C., Arró, M., Boronat, A. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  26. Transcriptional derepression of the murine Cyp1a-1 gene by mevinolin. Puga, A., Raychaudhuri, B., Nebert, D.W. FASEB J. (1992) [Pubmed]
  27. Molecular analysis of the MVK and TNFRSF1A genes in patients with a clinical presentation typical of the hyperimmunoglobulinemia D with periodic fever syndrome: a low-penetrance TNFRSF1A variant in a heterozygous MVK carrier possibly influences the phenotype of hyperimmunoglobulinemia D with periodic fever syndrome or vice versa. Stojanov, S., Lohse, P., Lohse, P., Hoffmann, F., Renner, E.D., Zellerer, S., Kéry, A., Shin, Y.S., Haas, D., Hoffmann, G.F., Belohradsky, B.H. Arthritis Rheum. (2004) [Pubmed]
  28. Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs. Jomaa, H., Wiesner, J., Sanderbrand, S., Altincicek, B., Weidemeyer, C., Hintz, M., Türbachova, I., Eberl, M., Zeidler, J., Lichtenthaler, H.K., Soldati, D., Beck, E. Science (1999) [Pubmed]
  29. Inhibition of protein isoprenylation and p21ras membrane association by dehydroepiandrosterone in human colonic adenocarcinoma cells in vitro. Schulz, S., Nyce, J.W. Cancer Res. (1991) [Pubmed]
  30. Cholesterol starvation decreases p34(cdc2) kinase activity and arrests the cell cycle at G2. Martínez-Botas, J., Suárez, Y., Ferruelo, A.J., Gómez-Coronado, D., Lasuncion, M.A. FASEB J. (1999) [Pubmed]
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