Advertisement

Pharmaceutisch Weekblad

, Volume 5, Issue 6, pp 291–297 | Cite as

The kinetics of the enzymatic O-methylation of catechols and catecholamines

  • M. T. I. W. Schüsler-Van Hees
  • G. M. J. Beijersbergen Van Henegouwen
Original Articles

Abstract

The enzymaticO-methylation of twelve catecholamines and two catechols was studied. From initial reaction rates Km and Vmax were determined. Under the reaction conditions applied the enzymaticO-methylation appears to be first order in the concentration of catechol(amine). For all twelve catecholamines and the two catechols the Km and Vmax based on initial reaction rates are equal to those from the ln(c/co) plots (= first-order kinetics). This fact and the variation of kobs (reaction rate constant in the first-order kinetics) with the starting concentration comply with the formulae derived for these kinetics. The variation of kobs is caused by product inhibition. From the formulae it follows that Ki (inhibition constant) = Km; this is confirmed by the experimental data. The polarity of the compounds seems to contribute to the reaction rate at low substrate concentration; the linear relationship between this value and log D may support an apolar region in the binding part of catechol-O-methyltransferase, without denying other contributing factors.

Keywords

Public Health Experimental Data Internal Medicine Linear Relationship Catecholamine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bates, R.G. (1962)J. Research 66A, 179–184.Google Scholar
  2. Corrigan, J.R., M.-J. Langermann andM.L. Moore (1945)J. Am. Chem. Soc. 67, 1894–1896;Ibidem (1949)71, 530–531.Google Scholar
  3. Coward, J.K., E.P. Slisz andY.-H. Wu (1973)Biochemistry 12, 2291–2297.Google Scholar
  4. Creveling, C.R., N. Morris, H. Shimizu, H.H. Ong andJ.W. Daly (1972)Mol. Pharmacol. 8, 398–409.Google Scholar
  5. Daly, J.E., J. Axelrod andB. Witkop (1960)J. Biol. Chem. 235, 1155–1159.Google Scholar
  6. Dixon, M., andE.C. Webb (1969) In:Enzymes Third Edition. Longman Group Ltd. London. Chapter iv and P. 334.Google Scholar
  7. Frère, J.M., andW.G. Verly (1971)Biochim. Biophys. Acta 235, 73–84.Google Scholar
  8. Kindler, K., andW. Peschke (1932)Arch. Pharm. 270, 340–353.Google Scholar
  9. Kuehl Jr., F.A., M. Hichens, R.E. Ormond, M.A.P. Meisinger, P.H. Gale, V.J. Cirillo andN.G. Brink (1964)Nature 203, 154–155.Google Scholar
  10. La Manna, A., andA. Campiglio (1959)Farmaco [Sci.] 14 317–322.Google Scholar
  11. Mack, F., andH. Bönisch (1979)Naunyn-Schmiedebergs Arch. Exp. Pathol. Pharmakol. 310, 1–9.Google Scholar
  12. Payne, K.R. (1961)Industrial Chemist 37, 523–527.Google Scholar
  13. Scherrer, R., andS.M. Howard (1977)J. Med. Chem. 20, 53–58.Google Scholar
  14. Schüsler-Van Hees, M.T.I.W., andG.M.J. Beijersbergen Van Henegouwen (1980)J. Chromatogr. 196, 101–108.Google Scholar
  15. Schüsler-Van Hees, M.T.I.W., andG.M.J. Beijersbergen Van Henegouwen (1982)Pharm. Weekbl. [Sci.] 4, 176–182.Google Scholar
  16. Schüsler-Van Hees, M.T.I.W., G.M.J. Beijersbergen Van Henegouwen andM.F.J. Driever (1983)Pharm. Weekbl. [Sci.] 5, 102–108.Google Scholar

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 1983

Authors and Affiliations

  • M. T. I. W. Schüsler-Van Hees
    • 1
  • G. M. J. Beijersbergen Van Henegouwen
    • 1
  1. 1.Subfaculty of PharmacyState University of Leiden, Gorlaeus LaboratoriesRA LeidenThe Netherlands

Personalised recommendations