Inhibition of tryptophan hydroxylase by 6,7-dihydroxy-N-cyanomethyl-1,2,3,4-tetrahydroisoquinoline, a cyanomethyl derivative of dopamine formed from cigarette smoke.
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.
Minami
M
M
Nagoya University School of Medicine, Japan.
Yu
P H
PH
Davis
B A
BA
Takahashi
T
T
Shimomura
Y
Y
Naoi
M
M
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
D007546:Isoquinolines; D012906:Smoke; D044005:Tetrahydroisoquinolines; C084554:6,7-dihydroxy-N-cyanomethyl-1,2,3,4-tetrahydroisoquinoline; D014365:Tryptophan Hydroxylase; D004298:Dopamine