Catecholamine metabolism in the brain by membrane-bound and soluble catechol-o-methyltransferase (COMT) estimated by enzyme kinetic values

• Published in: Medical hypotheses Vol. 57; no. 5; pp. 628 - 632
• Main Authors: Reenilä, I., Männistö, P.T.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Ltd 01.11.2001; Elsevier
• Subjects: Animals; Biological and medical sciences; Brain - enzymology; Brain - metabolism; Catechol O-Methyltransferase - metabolism; Catecholamines - metabolism; Cell Membrane - enzymology; Dopamine - metabolism; Enzymes. Coenzymes. Vitamins. Pigments; Fundamental and applied biological sciences. Psychology; Humans; Kinetics; Metabolisms and neurohumoral controls; Norepinephrine - metabolism; Rats; Solubility; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Human; Dopamine; Rat; Enzyme; Transferases; Rodentia; Catechol O-methyltransferase; Catecholamine; Experimental study; Metabolism; Kinetic model; Vertebrata; Mammalia; Methyltransferases; Animal; Norepinephrine; Comparative study; Brain (vertebrata)
• ISSN: 0306-9877; 1532-2777
• DOI: 10.1054/mehy.2001.1430

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.