Inhibition of catechol-O-methyltransferase by N-(3,4-dihydroxyphenyl) maleimide.
Catechol-O-methyltransferase (COMT) is inhibited rapidly and irreversibly by N-(3,4-dihydroxyphenyl) maleimide. S-adenosylmethionine (AdoMet) and magnesium ions protect the enzyme from inactivation by this compound, but no protection is observed by the catechol substrate. However, the corresponding succinimide analogue shows a reversible inhibition of COMT, which is competitive with pyrocatecholphthalein and non-competitive with AdoMet. Amino-group reagents also inhibit COMT and this inhibition is protected by AdoMet, suggesting that sulphydryl and amino groups essential for activity are located in an AdoMet-binding site on COMT. The maleimide derivative may be considered to be an active-site directed inhibitor.
Piedrafita
F J
FJ
Instituto de Química Orgánica General del C.S.I.C., Madrid, Spain.
Elorriaga
C
C
Fernández-Alvarez
E
E
Nieto
O
O
D000818:Animals; D001667:Binding, Competitive; D002394:Catechol O-Methyltransferase / Q000302:isolation & purification; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D008274:Magnesium / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology*; D015394:Molecular Structure; D013552:Swine; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D008301:Maleimides; C068975:N-(3,4-dihydroxyphenyl)maleimide; D002394:Catechol O-Methyltransferase; D013890:Thiourea; D008274:Magnesium