Inhibition of monoamine oxidase by 3,4-dihydroxyphenyl L-alanine and its analogues.
L-3,4-Dihydroxyphenylalanine (DOPA) was found to inhibit type A monoamine oxidase in human placental mitochondria. The inhibition proved to be noncompetitive with the substrate, kynuramine, and the inhibition was completely reversible. D-DOPA was found to inhibit monoamine oxidase in the same way, and the apparent Ki values of L- and D-DOPA were obtained to be 154 microM and 133 microM, respectively. L-alpha-Methyl-DOPA was found to inhibit the MAO activity competitively with the substrate, but studies with other analogues of DOPA revealed that the inhibition required an amino and a carboxyl group at alpha-position. The substitution of a hydroxy group at 3 or 4 position of catechol ring with a methoxy group was found to abolish the inhibition of the MAO activity. In addition to type A MAO in human liver and placental mitochondria, type B MAO in liver mitochondria was inhibited by L-DOPA, but type B MAO was less sensitive to L-DOPA. These results were discussed in terms of its possible regulation of the level of biogenic amines in the brain.
D004295:Dihydroxyphenylalanine / Q000494:pharmacology; D015103:Droxidopa / Q000031:analogs & derivatives / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007735:Kynuramine / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology*; D008750:Methyldopa / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D008996:Monoamine Oxidase Inhibitors; D010920:Placenta / Q000187:drug effects / Q000201:enzymology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D008996:Monoamine Oxidase Inhibitors; D007735:Kynuramine; D007980:Levodopa; D008750:Methyldopa; D004295:Dihydroxyphenylalanine; C051259:3-(3,4-dihydroxyphenyl)-N-methylserine; D015103:Droxidopa