title: Inhibition of tryptophan hydroxylase by 6,7-dihydroxy-N-cyanomethyl-1,2,3,4-tetrahydroisoquinoline, a cyanomethyl derivative of dopamine formed from cigarette smoke.
abstract: 6,7-Dihydroxy-N-cyanomethyl-1,2,3,4-tetrahydroisoquinoline, a cyanomethyl derivative of dopamine formed from cigarette smoke, was found to inhibit the activity of tryptophan hydroxylase. The inhibition was non-competitive to the substrate L-tryptophan (the Ki value 7.25 +/- 0.81 microM), but not to the biopterin cofactor. The inhibition is irreversible. 6-Hydroxy-N-cyanomethyl-tetrahydro-beta-carboline, a cyanomethyl derivative of serotonin, is inactive towards the hydroxylase. 6,7-Dihydroxy-N-cyanomethyl-1,2,3,4-tetrahydroisoquinoline may affect the serotonin biosynthesis in vivo as a consequence of cigarette smoking.
authors.affiliation: Nagoya University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Minami
authors.forename: P H
authors.initials: PH
authors.lastname: Yu
authors.forename: B A
authors.initials: BA
authors.lastname: Davis
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Shimomura
authors.forename: M
authors.initials: M
authors.lastname: Naoi
mesh_terms: D000818:Animals; D001921:Brain / Q000201:enzymology*; D002850:Chromatography, Gel; D004298:Dopamine; D007546:Isoquinolines; D007700:Kinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012906:Smoke; D044005:Tetrahydroisoquinolines; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification
chemical_list: D007546:Isoquinolines; D012906:Smoke; D044005:Tetrahydroisoquinolines; C084554:6,7-dihydroxy-N-cyanomethyl-1,2,3,4-tetrahydroisoquinoline; D014365:Tryptophan Hydroxylase; D004298:Dopamine