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 .apprx. 7.25, as was the case with the 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 .mu.M and 0.29 .+-. 0.06 pmol/min/mg protein, and 463 .+-. 43 .mu.M and 0.16 .+-. 0.003 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 kynurmaine. NMITQ was the first tetrahydroisoquinoline shown to be oxidized into the isoquinolinium ion by MAO in the brain.