L-DOPA biotransformation

Correlations of dosage, erythrocyte catechol O-methyltransferase and platelet SULT1A3 activities with metabolic pathways in Parkinsonian patients

M. K. Dousa, Richard M Weinshilboum, M. D. Muenter, K. P. Offord, P. A. Decker, G. M. Tyce

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The objectives of this study were to determine (1) the effects of dose and drug absorption on pathways of biotransformation of L-DOPA in Parkinsonian patients treated with Sinemet, and (2) the extent to which genetically-determined variations in the activities of erythrocyte catechol O-methyltransferase and/or platelet phenol sulfotransferase might be reflected in individual differences in L-DOPA metabolism. In the 19 patients studied, there were negative correlations between dosage or absorption and extent of O-methylation and of sulfation of L-DOPA or its metabolites. Levels of activity for erythrocyte COMT were also reflected in individual variation in the metabolism of L-DOPA. In contrast, differences in platelet phenol sulfotransferase were not reflected in differences in sulfation of L-DOPA or of its metabolites. If such a relationship did exist, it might have been obscured by the effects of high dosage of L-DOPA, effects which might have resulted from a deficiency of the sulfation cosubstrate 3′-phosphoadenosine 5′-phosphosulfate in patients taking higher doses of drug.

Original languageEnglish (US)
Pages (from-to)899-910
Number of pages12
JournalJournal of Neural Transmission
Volume110
Issue number8
DOIs
StatePublished - Aug 1 2003

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Catechol O-Methyltransferase
Arylsulfotransferase
Biotransformation
Metabolic Networks and Pathways
Blood Platelets
Erythrocytes
Phosphoadenosine Phosphosulfate
Individuality
Pharmaceutical Preparations
Methylation
monoamine-sulfating phenol sulfotransferase

Keywords

  • 3′-phosphoadenosine 5′-phosphosulfate
  • L-DOPA absorption
  • L-DOPA:biotransformation
  • L-DOPA:pharmacogenomics
  • S-adenosyl-L-methionine

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

L-DOPA biotransformation : Correlations of dosage, erythrocyte catechol O-methyltransferase and platelet SULT1A3 activities with metabolic pathways in Parkinsonian patients. / Dousa, M. K.; Weinshilboum, Richard M; Muenter, M. D.; Offord, K. P.; Decker, P. A.; Tyce, G. M.

In: Journal of Neural Transmission, Vol. 110, No. 8, 01.08.2003, p. 899-910.

Research output: Contribution to journalArticle

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