These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Substrate stereospecificity and selectivity of catechol-O-methyltransferase for DOPA, DOPA derivatives and alpha-substituted catecholamines.
    Author: Gordonsmith RH, Raxworthy MJ, Gulliver PA.
    Journal: Biochem Pharmacol; 1982 Feb 01; 31(3):433-7. PubMed ID: 6803810.
    Abstract:
    The substrate specificity of highly purified pig liver catechol-O-methyltransferase has been investigated kinetically. This enzyme shows stereospecificity towards the naturally occurring L-isomer of 3,4-dihydroxyphenylalanine (DOPA) which has a higher affinity and maximal velocity as a substrate than the D-form. We have confirmed the implication of the in vivo study of Ito et al. [1], that methylation of 5-S-L-cysteinyl-L-DOPA is catalysed extremely slowly by catechol-O-methyltransferase, despite the comparatively high affinity of the enzyme for the substrate. Salbutamol is not a substrate for the enzyme and DL-threo-3,4-dihydroxyphenylserine (DOPS) is such a poor substrate that accurate kinetic analysis proved impossible. Alpha-substitution of DOPA, noradrenaline and isoprenaline causes a decrease in the affinity of catechol-O-methyltransferase for these compounds. However, the "suicide' inhibitors of aromatic-L-amino acid decarboxylase (DOPA decarboxylase), fluoro- and difluoro-alpha-methyl DOPA are more superior catechol-O-methyltransferase substrates than alpha-methyl DOPA, presumably because the electron-withdrawing effect of the presence of fluorine in their structure overcomes the steric influence of the alpha-methyl group. A DOPA decarboxylase inhibitor in clinical use, benserazide, is, however, a much superior catechol-O-methyltransferase substrate and may have the therapeutic advantage of decreasing methylation of L-DOPA [2]. Alpha-Methyl dopamine has a lower Km and higher Vmax than the parent compound.
    [Abstract] [Full Text] [Related] [New Search]