Neurotoxins: 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1,2,3,4-tetrahydroisoquinoline and 1-methyl-6,7-dihydroxy-tetrahydroisoquinoline as substrates for FAD-containing monooxygenase of porcine liver microsomes.
The activity of FAD-containing monooxygenase (FMO) (EC 1.14.13.8) of porcine liver microsomes was examined with the neurotoxins, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1,2,3,4-tetrahydroisoquinoline (TIQ) and 1-methyl-6,7-dihydroxy-tetrahydroisoquinoline (MDTIQ), as substrates. FMO catalyses these neurotoxins. The kinetic parameters of FMO for the neurotoxins and electron donors were determined. Km values for MPTP, TIQ and MDTIQ were determined to be 47 microM, 6.9 mM and 5.6 mM, respectively. The Km for the electron donor, NADPH, was variable from 31 to 200 microM depending on the substrate used. The activities of FMO for these neurotoxins were comparable with that for dimethylaniline.
Wu
R F
RF
Department of Biochemistry, Kagawa Medical School, Kagawa 761-07, Japan.
Miura
S
S
Ichikawa
Y
Y
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000378:metabolism*; D000818:Animals; D007546:Isoquinolines / Q000378:metabolism*; D007700:Kinetics; D008862:Microsomes, Liver / Q000201:enzymology*; D009249:NADP / Q000378:metabolism; D009498:Neurotoxins / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism*; D013552:Swine; D044005:Tetrahydroisoquinolines
D007546:Isoquinolines; D009498:Neurotoxins; D044005:Tetrahydroisoquinolines; D009249:NADP; C014843:1,2,3,4-tetrahydroisoquinoline; C036617:salsolinol; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming)