Mechanism of reaction of allylamine with the quinoprotein methylamine dehydrogenase.
Mechanism of reaction of allylamine with the quinoprotein methylamine dehydrogenase.
复制标题
烯丙胺与醌蛋白甲胺脱氢酶的反应机制。
DOI：
10.1042/bj3080487
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Jones,LH
中科院分区：
文献类型：
--
作者：
Davidson,VL;Graichen,ME;Jones,LH
在稳态活性测定中，烯丙胺不能作为甲胺脱氢酶（EC 1.4.99.3）的有效底物，并且似乎充当甲胺脱氢酶氧化甲胺的竞争性抑制剂。然而，瞬时动力学研究表明，烯丙胺迅速降低甲胺脱氢酶的色氨酸色氨酸醌 (TTQ) 辅因子。烯丙胺还原TTQ的速率为322s-1，略快于甲胺还原的速率。这些数据可以通过动力学机制来解释，其中烯丙胺和甲胺是甲胺脱氢酶的替代底物。烯丙胺的明显竞争性抑制是由于醛产物的释放速率非常慢，为 0.28 s-1，而甲胺氧化的醛产物的释放速率为 18.6 s-1。提出了甲胺脱氢酶对烯丙胺进行氧化脱氨的反应机理。结合托帕醌蛋白胺氧化酶、黄素蛋白单胺氧化酶和哺乳动物氨基脲敏感胺氧化酶的反应机制讨论了该机制。
Allylamine did not serve as an efficient substrate for methylamine dehydrogenase (EC 1.4.99.3) in a steady-state assay of activity and appeared to act as a competitive inhibitor of methylamine oxidation by methylamine dehydrogenase. Transient kinetic studies, however, revealed that allylamine rapidly reduced the tryptophan tryptophylquinone (TTQ) cofactor of methylamine dehydrogenase. The rate of TTQ reduction by allylamine was 322 s-1, slightly faster than the rate of reduction by methylamine. These data were explained by a kinetic mechanism in which allylamine and methylamine are alternative substrates for methylamine dehydrogenase. The apparent competitive inhibition by allylamine is due to a very slow rate of release of the aldehyde product, 0.28 s-1, relative to a rate of 18.6 s-1 for the release of the aldehyde product of methylamine oxidation. A reaction mechanism is proposed for the oxidative deamination of allylamine by methylamine dehydrogenase. This mechanism is discussed in relation to the reaction mechanisms of topa-bearing quinoprotein amine oxidases, the flavoprotein monoamine oxidase and the mammalian semicarbazide-sensitive amine oxidase.