Catechol-O-methyltransferase and aromatic L-amino acid decarboxylase activities in human gastrointestinal tissues.
Human gastrointestinal samples from the corpus, antrum, bulbus, jejunum and ileum were assayed for soluble and membrane-bound catechol-O-methyltransferase (COMT) and aromatic L-amino acid decarboxylase (AADC) activity in vitro. The mean soluble COMT activities with 3,4-dihydroxybenzoic acid (DBA) and 3,4-dihydroxyphenylalanine (L-DOPA) as substrate were 70-242 and 70-174 pmol/min mg, respectively. The membrane-bound COMT activities ranged from 33 to 60 pmol/min mg in the different parts of the intestine. The AADC activities, measured with L-DOPA as the substrate, increased from 114 pmol/min mg in the corpus to 3488 pmol/min mg in the jejunum. The affinity of the soluble COMT was approximately 20 times higher for DBA (Km 15-19 microM) than for L-DOPA (Km 300-600 microM). The Km-values for L-DOPA of AADC and COMT were of the same order of magnitude. The specific COMT inhibitors, nitecapone and OR-611, effectively inhibited in vitro the human intestinal COMT activity. Nanomolar concentrations caused 50% inhibition with both DBA and L-DOPA as substrate.
Schultz
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Orion Pharmaceutica, Research Center, Espoo, Finland.
D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D002394:Catechol O-Methyltransferase / Q000378:metabolism*; D004064:Digestive System / Q000201:enzymology*; D006801:Humans; D007082:Ileum / Q000201:enzymology; D007583:Jejunum / Q000201:enzymology; D007980:Levodopa / Q000378:metabolism; D013270:Stomach / Q000201:enzymology
D007980:Levodopa; D002394:Catechol O-Methyltransferase; D001142:Aromatic-L-Amino-Acid Decarboxylases