Enzymatic oxidation of the dopaminergic neurotoxin, 1(R), 2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, into 1,2(N)-dimethyl-6,7-dihydroxyisoquinolinium ion.
The dopamine-derived alkaloid, 1(R),2(N)-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline [N-methyl(R)salsolinol] was found to be oxidized enzymatically into the more cytotoxic species, 1,2(N)-dimethyl-6,7-dihydroxyisoquinolinium ion, using enzyme sample prepared from human brain cortex. The values of the Michaelis constant and of the maximum velocity were 912 microM and 1,368 pmol/min/mg protein, respectively. The enzyme was not inhibited by inhibitors of monoamine oxidase, but was sensitive to semicarbazide. The oxidation is discussed in relation to the dopaminergic neurotoxicity of N-methyl-(R)salsolinol.
Naoi
M
M
Department of Biosciences, Nagoya Institute of Technology, Japan.
Maruyama
W
W
Zhang
J H
JH
Takahashi
T
T
Deng
Y
Y
Dostert
P
P
D002451:Cell Compartmentation; D002540:Cerebral Cortex / Q000201:enzymology*; D003010:Clorgyline / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000378:metabolism*; D007700:Kinetics; D009498:Neurotoxins / Q000378:metabolism*; D010084:Oxidation-Reduction; D012642:Selegiline / Q000494:pharmacology; D012663:Semicarbazides / Q000494:pharmacology
D007546:Isoquinolines; D009498:Neurotoxins; D012663:Semicarbazides; D012642:Selegiline; C010059:carbamylhydrazine; C036617:salsolinol; D003010:Clorgyline