title: Oxidation of N-methyl-1,2,3,4-tetrahydroisoquinoline into the N-methyl-isoquinolinium ion by monoamine oxidase.
abstract: N-Methyl-1,2,3,4-tetrahydroisoquinoline (NMTIQ) was found to be oxidized by monoamine oxidase (MAO) into N-methylisoquinolinium ion, which was proved to inhibit enzymes related to the metabolism of catecholamines, such as tyrosine hydroxylase, aromatic-L-amino acid decarboxylase, and MAO. NMTIQ was oxidized by both types A and B MAO in human brain synaptosomal mitochondria. Oxidation was dependent on the amount of MAO sample and the reaction time. Enzyme activity with respect to NMTIQ reached optimum at a pH of approximately 7.25, as was the case with other substrates. Type A MAO had higher activity for this substrate than type B. The Km and Vmax values of the oxidation by types A and B MAO were 571 +/- 25 microM and 0.29 +/- 0.06 pmol/min/mg protein, and 463 +/- 43 microM and 0.16 +/- 0.03 pmol/min/mg protein, respectively. The Vmax values of types A and B MAO for NMTIQ were much smaller than those for other substrates such as kynuramine. NMTIQ was the first tetrahydroisoquinoline shown to be oxidized into the isoquinolinium ion by MAO in the brain.
authors.affiliation: Department of Biochemistry, Nagoya University School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Naoi
authors.forename: S
authors.initials: S
authors.lastname: Matsuura
authors.forename: H
authors.initials: H
authors.lastname: Parvez
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: Y
authors.initials: Y
authors.lastname: Hirata
authors.forename: M
authors.initials: M
authors.lastname: Minami
authors.forename: T
authors.initials: T
authors.lastname: Nagatsu
mesh_terms: D001921:Brain / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007546:Isoquinolines / Q000378:metabolism*; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors; D010084:Oxidation-Reduction; D011806:Quinolinium Compounds / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013053:Spectrophotometry; D013574:Synaptosomes / Q000201:enzymology*; D044005:Tetrahydroisoquinolines
chemical_list: D007546:Isoquinolines; D008996:Monoamine Oxidase Inhibitors; D011806:Quinolinium Compounds; D044005:Tetrahydroisoquinolines; C051351:N-methylisoquinolinium; C050386:1-methyl-1,2,3,4-tetrahydroisoquinoline; D008995:Monoamine Oxidase