Monoamine Oxidaseに関する研究-90-ラット脳および肝mitochondria MAOの基質特異性

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Concentration-dependent changes in substrate specificity of rat brain and liver mitochondrial MAO were studied, using β-phenylethylamine (PEA), serotonin (5-HT), benzylamine, tyramine, dopamine and tryptamine as substrates, by the experiments with inhibition patterns of activity by clorgyline. Double-sigmoidal curves of activity for clorgyline towards tyramine, dopamine and tryptamine, irrespective of the concentractions used, were obtained, indicating oxidations by both MAO-A and MAO-B. However, the curves with low concentrations (0.01-0.05 mM) of 5-HT were single-singmoidal and highly sensitive to clorgyline, whereas, with the higher concentrations (0.5-5 mM), the curves changed to double-sigmoidal. These findings indicate oxidation of 5-HT at low concentrations by only MAO-A, but at high concentrations by both forms of MAO. These concentration-dependent changes in substrate-specificity were also observed with PEA as substrate ; the curves towards the low concentrations were single-sigmoidal and less sensitive to clorgyline (MAO-B), whereas with the higher concentrations (0.1-5 mM), the curves became Double-sigmoidal (oxidized by both forms) . With untreated and clorgyline-treated mitochondria, Lineweaver-Burk plots showed increase in PEA oxidation with increase in O<SUB>2</SUB> tensions with parallel lines, indicating a ping-pong reaction mechanism. These results indicate that substrate concentrations must be taken into account when the substrate specificities and inhibitor sensitivities are investigated.
学校法人昭和大学・昭和医学会の論文

Monoamine Oxidaseに関する研究-90-ラット脳および肝mitochondria MAOの基質特異性

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