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Hydroxymethylglutaryl-CoA reductase, a key enzyme in phytosterol synthesis?

  • Papers from the H. W. Kircher Memorial Symposium on Chemistry Biosynthesis and Function of Sterols Presented at the 76th AOCS Annual Meeting in Philadelphia, Pennsylvania, May 1985
  • Published:
Lipids

Abstract

Hydroxymethylglutaryl-CoA reductase (HMGR) regulates the synthesis of mevalonic acid (MVA), the precursor of the myriad of isoprenoid compounds functional in plant cells, with phytosterols representing one class of major importance. Recently, it has shown possible to solubilize and purify the membrane-bound enzyme from a heavy membrane fraction (P 16,000×g) isolated from a cell-free homogenate of etiolated radish seedlings. What is presently known about the molecular and kinetic properties of radish HMGR is reported.

Mevinolin, a highly specific competitive inhibitor of HMGR, has been valuable as a research tool in studying the regulatory role of HMGR activity for the growth and development of intact seedlings and cell cultures. The results obtained indicate a primary effect of mevinolin on phytosterol accumulation, whereas other endproducts of the multibranched isoprenoid pathway, such as ubiquinone in the mitochondria or chlorophylls and carotenoids in the plastids, are less or not at all affected. This and other data can be interpreted to mean that the organelles are autonomous in their capacity to synthesize MVA. Since the mevinolin-induced drop in free sterol accumulation is paralleled by significant plant growth retardation, a rate-limiting role of HMGR activity for phytosterol synthesis and normal development of plants is suggested.

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References

  1. Rodwell, V.W., Nordstrom, J.L., and Mitschelen, J.J. (1976)Adv. Lipid Res. 14, 1–74.

    PubMed  CAS  Google Scholar 

  2. Dugan, R.E. (1981) inBiosynthesis of Isoprenoid Compounds (Porter, J.W., and Spurgeon, S.L., eds.) Vol. I, pp. 95–159, John Wiley & Sons, New York.

    Google Scholar 

  3. Schroepfer, G. Jr. (1981)Annu. Rev. Biochem. 50, 585–621.

    Article  PubMed  CAS  Google Scholar 

  4. Chang, T.-Y. (1983)The Enzymes 16, 491–521.

    CAS  Google Scholar 

  5. Sabine, J.R., ed.) (1983)Monographs on Enzyme Biology: HMG-CoA Reductase, CRC Press, Boca Raton.

    Google Scholar 

  6. Preiss, B., ed. (1985)Regulation of HMG-CoA Reductase, Academic Press, New York.

    Google Scholar 

  7. Goodwin, T.W. (1958)Biochem. J. 68, 26–27.

    Google Scholar 

  8. Goodwin, T.W. (1958)Biochem. J. 70, 612–617.

    PubMed  CAS  Google Scholar 

  9. Berry, D.L., Singh, B., and Salunkhe, D.K. (1972)Plant Cell Physiol. 13, 157–165.

    CAS  Google Scholar 

  10. Hepper, C.M., and Audley, B.G. (1969)Biochem. J. 114, 379–386.

    PubMed  CAS  Google Scholar 

  11. Lynen, F. (1967)Pure Appl. Chem. 14, 137.

    PubMed  CAS  Google Scholar 

  12. Brooker, J.D., and Russell, D.W. (1975)Arch. Biochem. Biophys. 167, 723–729.

    Article  PubMed  CAS  Google Scholar 

  13. Brooker, J.D., and Russell, D.W. (1975)Arch. Biochem. Biophys. 167, 723–729.

    Article  PubMed  CAS  Google Scholar 

  14. Brooker, J.D., and Russell, D.W. (1975)Arch. Biochem. Biophys. 198, 323–334.

    Article  Google Scholar 

  15. Russell, D.W., and Davidson, H. (1982)Biochem. Biophys. Res. Commun. 104, 1537–1543.

    Article  PubMed  CAS  Google Scholar 

  16. Wong, R.J., McCormack, D.K., and Russell, D.W. (1982)Arch. Biochem. Biophys. 216, 631–638.

    Article  PubMed  CAS  Google Scholar 

  17. Suzuki, H., Uritani, I., and Oba, K. (1975)Physiol. Plant. Pathol. 7, 265–276.

    Article  CAS  Google Scholar 

  18. Suzuki, H., Oba, K., and Uritani, I. (1976)Plant Cell Physiol. 17, 691–700.

    CAS  Google Scholar 

  19. Suzuki, H., and Uritani, I. (1977)Plant Cell Physiol. 18, 485–495.

    CAS  Google Scholar 

  20. Ito, R., Oba, K., and Uritani, I. (1979)Plant Cell Physiol. 20, 867–874.

    CAS  Google Scholar 

  21. Grumbach, K.H., and Bach, T.J. (1979)Z. Naturforsch. 34c, 941–943.

    CAS  Google Scholar 

  22. Bach, T.J., Lichtenthaler, H.K., and Retey, J. (1980) inBiogenesis and Function of Plant Lipids (Mazliak, P., Benveniste, P., Costes, C., and Douce, R., eds.) pp. 355–362, Elsevier, Amsterdam.

    Google Scholar 

  23. Bach, T.J. (1981)Karlsruher Beitr Pflanzenphysiol. 10, 1–219.

    Google Scholar 

  24. Bach, T.J., and Rudney, H. (1983)J. Lipid Res. 24, 1404–1405(A).

    Google Scholar 

  25. Bach, T.J., and Lichtenthaler, H.K. (1984)Biochim. Biophys. Acta 794, 152–161.

    PubMed  CAS  Google Scholar 

  26. Bach, T.J., Rogers, D.H., and Rudney, H. (1984) inStructure, Function and Metabolism of Plant Lipids (Siegenthaler, P.-A., and Eichenberger, W., eds.) pp. 221–224, Elsevier, Amsterdam.

    Google Scholar 

  27. Sipat, A.B. (1981)Biochim. Biophys. Acta 705, 284–287.

    Google Scholar 

  28. Mohd, R.B., and Sipat, A.B. (1982)Biochim. Biophys. Res. Commun. 108, 206–212.

    Article  Google Scholar 

  29. Sipat, A.B. (1982)Phytochemistry 21, 2613–2618.

    Article  CAS  Google Scholar 

  30. Kreuz, K., Kleinig, H. (1984)Eur. J. Biochem. 141, 531–535.

    Article  PubMed  CAS  Google Scholar 

  31. Arebalo, R.E., and Mitchell, E.D. Jr. (1984)Phytochemistry 23, 13–18.

    Article  CAS  Google Scholar 

  32. Nishi, A., and Tsuritani, I. (1983)Phytochemistry 22, 399–401.

    Article  CAS  Google Scholar 

  33. Leube, J., and Grisebach, H. (1983)Z. Naturforsch. 38c, 730–735.

    CAS  Google Scholar 

  34. Camara, B., Bardat, F., Dogbo, O., Brangeon, J., and Monéger, R. (1983)Plant Physiol. 73, 94–99.

    Article  PubMed  CAS  Google Scholar 

  35. Alberts, A.W., Chen, J., Kuron, G., Hunt, V., Huff, J., Hoffman, C., Rothrock, J., Lopez, M., Joshua, H., Harris, E., Patchett, A., Monagan, R., Currie, S., Stapley, E., Albers-Schönberg, G., Hensens, O., Hirschfield, J., Hoogsteen, K., Liesch, J., and Springer, J. (1980)Proc. Natl. Acad. Sci. USA 77, 3957–3961.

    Article  PubMed  CAS  Google Scholar 

  36. Bach, T.J., and Lichtenthaler, H.K. (1982)Z. Naturforsch. 37c, 46–50.

    CAS  Google Scholar 

  37. Bach, T.J., and Lichtenthaler, H.K. (1983)Z. Naturforsch. 38c, 212–219.

    CAS  Google Scholar 

  38. Endo, A. (1981)Methods Enzymol. 71, 684–689.

    Google Scholar 

  39. Brown, M.S., and Goldstein, J.L. (1980)J. Lipid. Res. 21, 505–517.

    PubMed  CAS  Google Scholar 

  40. Fears, R. (1983)Biochem. Soc. Transact. 11, 642–644.

    CAS  Google Scholar 

  41. Chin, D.J., Gil, G., Russell, D.W., Liscum, L., Luskey, K.L., Basu, S.K., Okayama, H., Berg, P., Goldstein, J.L., and Brown, M.S. (1984)Nature 308, 613–617.

    Article  PubMed  CAS  Google Scholar 

  42. Bach, T.J., and Lichtenhaler, H.K. (1982) inBiochemistry and Metabolism of Plant Lipids (Wintermans, J.F.G.M., and Kuiper, P.J.C., eds.) pp. 515–522, Elsevier, Amsterdam.

    Google Scholar 

  43. Bach, T.J., and Lichtenthaler, H.K. (1983)Physiol. Plant. 59, 50–60.

    Article  CAS  Google Scholar 

  44. Schindler, S., Bach, T.J., and Lichtenthaler, H.K. (1985)Z. Naturforsch. 40c, 208–214.

    CAS  Google Scholar 

  45. Kreuz, K., Beyer, P., and Kleinig, H. (1982)Planta 154, 66–69.

    Article  CAS  Google Scholar 

  46. Lütke-Brinkhaus, F., Liedvogel, B., and Kleinig, H. (1984)Eur. J. Biochem. 141, 537–541.

    Article  PubMed  Google Scholar 

  47. Bach, T.J., Rogers, D.H., and Rudney, H., Eur. J. Biochem., in press.

  48. Kita, T., Brown, M.S., and Goldstein, J.L. (1980)J. Clin. Invest. 66, 1094–1100.

    PubMed  CAS  Google Scholar 

  49. Beg, Z.H., Stonik, J.A., and Brewer, H.B. (1977)FEBS Lett. 80, 123–129.

    Article  PubMed  CAS  Google Scholar 

  50. Kleinsek, D.A., Jabalquinto, A.M., and Porter, J.W. (1977)Proc. Natl. Acad. Sci. USA 74, 1431–1435.

    Article  PubMed  CAS  Google Scholar 

  51. Rogers, D.H., Panini, S.R., and Rudney, H. (1980)Anal. Biochem. 101, 107–111.

    Article  PubMed  CAS  Google Scholar 

  52. Ness, G.C., Way, S.C., and Wickham, P.S. (1981)Biochim. Biophys. Res. Commun. 102, 81–85.

    Article  CAS  Google Scholar 

  53. Kirtley, M.E., and Rudney, H. (1967)Biochemistry USA 6, 230–238.

    CAS  Google Scholar 

  54. Dotan, I., and Shechter, I. (1982)Biochim. Biophys. Acta 713, 427–434.

    PubMed  CAS  Google Scholar 

  55. Dotan, I., and Shechter, I. (1983)Arch. Biochem. Biophys. 226, 401–410.

    Article  PubMed  CAS  Google Scholar 

  56. Roitelman, J., and Shechter, I. (1984)J. Biol. Chem. 259, 870–877.

    PubMed  CAS  Google Scholar 

  57. Rogers, D.H., and Rudney, H. (1983)J. Lipid Res. 24, 1412.

    Google Scholar 

  58. Balange, A.P., and Lambert, C. (1983)Plant Sci. Lett. 32, 253–259.

    Article  CAS  Google Scholar 

  59. Fromm, H.J. (1975)Initial Rate Kinetics, Springer-Verlag, Berlin/Heidelberg/New York.

    Google Scholar 

  60. Cleland, W.W. (1967)Annu. Rev. Biochem. 36, 77–112.

    Article  CAS  PubMed  Google Scholar 

  61. Döll, M., Schindler, S., Lichtenthaler, H.K., and Bach, T.J. (1984) inStructure, Function and Metabolism of Plant Lipids (Siegenthaler, P.-A., and Eichenberger, W., eds.) pp. 277–280, Elsevier, Amsterdam.

    Google Scholar 

  62. Bach, T.J., and Lichtenthaler, H.K., inLipid Interactions Among Plants and Their Pathogens (Fuller, G., and Nes, W. D., eds.) Am. Chem. Soc. Symposium Series, ACS Washington, in press.

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Bach, T.J. Hydroxymethylglutaryl-CoA reductase, a key enzyme in phytosterol synthesis?. Lipids 21, 82–88 (1986). https://doi.org/10.1007/BF02534307

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