Catecholamine metabolism in the brain by membrane-bound and soluble catechol-o-methyltransferase (COMT) estimated by enzyme kinetic values.
A kinetic model was constructed to reevaluate the catecholamine metabolism in hypothetical brain homogenates. Earlier published kinetic values of recombinant membrane-bound (MB-) COMT and soluble (S-) COMT were combined with data suggesting that MB-COMT represents 70% and 30% of total COMT protein in human and rat brain, respectively. In the rat brain model L-DOPA and 3,4-dihydroxybenzoic acid were O-methylated mainly via S-COMT, while dopamine and noradrenaline, at low concentrations, were O-methylated slightly more by MB-COMT. In the human brain model dopamine and noradrenaline were metabolized primarily by MB-COMT. The ratio of meta (3-methoxy) over para (4-methoxy) product formation from 3,4-dihydroxybenzoic acid was higher for MB-COMT than S-COMT. It is suggested that MB-COMT clearly predominates the O-methylation of dopamine and noradrenaline also in vivo. Additionally, meta/para ratios could support the enrichment of either isoform of COMT in a homogenate sample.
Reenilä
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Department of Pharmacology and Toxicology, Institute of Biomedicine, Haarmaninkatu 8, Fin-00014, University of Helsinki, Finland. ilkka.reenila@helsinki.fi
Männistö
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D000818:Animals; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D012995:Solubility
D002395:Catecholamines; D002394:Catechol O-Methyltransferase; D004298:Dopamine; D009638:Norepinephrine