Methoxytyrosine formation as an indicator of catechol-O-methyltransferase activity in rat liver in vivo.
The O-methyl derivative methoxytyrosine accumulated rapidly in rat liver after an intraperitoneal injection of L-dopa (50 mg/kg) in combination with 3-hydroxybenzylhydrazine, an inhibitor of the aromatic amino acid decarboxylase. Methoxytyrosine levels reached a plateau 40--60 min after i.p. injection of L-dopa, of which the tissue concentration declined monoexponentially. Injection of various doses of L-dopa revealed that methoxytyrosine formation was saturable and followed enzyme kinetics in rat liver. The catechol-O-methyltransferase inhibitors pyrogallol, tropolone and alpha-propyldopacetamide as well as the inhibitor of the aromatic amino acid decarboxylase benserazide inhibited the formation of methoxytyrosine dose-dependently and concomitantly increased the tissue concentration of dopa. The accumulation of methoxytyrosine from exogeneously applied L-dopa appears to be a reliable indicator of the in vivo activity of catechol-O-methyltransferase.
D000596:Amino Acids; D000818:Animals; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D006834:Hydrazines / Q000494:pharmacology; D007980:Levodopa / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051381:Rats; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000096:biosynthesis
D000596:Amino Acids; D006834:Hydrazines; D014443:Tyrosine; D007980:Levodopa; D002394:Catechol O-Methyltransferase; D002262:Carboxy-Lyases