Severina I S
Biokhimiia. 1979 Feb;44(2):195-207.
The inhibition of the deamination of serotonin (the main substrate of monoamine oxidase (MAO) type A) by chlorgiline and deprenyl and of beta-phenylethylamine (the main substrate of the B type MAO) by fragments of rat liver mitochondrial membrane as well as the influence of 4-ethylpyridine on this process were studied. It was shown that the MAO activity of the mitochondrial membrane fragments was highly sensitive to chlorgiline, when serotonin was used as substrate, whereas a high sensitivity toward deprenyl was observed with beta-phenylethylamine as substrate. 4-Ethylpyridine (5.10(-3) M), a competitive and reversible inhibitor of the MAO activity, inhibited deamination of serotonin and beta-phenylethylamine by 34 and 30%, respectively. In experiments with chlorgiline (the specific inhibitor of MAO type A) 4-ethylpyridine (5.10(-3) M) introduced into the samples after preincubation of mitochondria with increasing concentrations of chlorgiline (30 min, 23 degrees C) decreased the inhibition by chlorgiline of the deamination of beta-phenylethylamine, but sharply increased the inhibitory effect of chlorgiline on the oxidation of serotonin. In analogous experiments with deprenyl (the specific inhibitor of MAO type B) 4-ethylpyridine (5.10(-3) M) decreased the inhibitory effect of deprenyl not only on the deamination of serotonin (substrate of MAO A), but also on the oxidation of beta-phenylethylamine (the main substrate of MAO type B). The decrease in the inhibitory effect of deprenyl on the deamination of beta-phenylethylamine after the addition of 4-ethylpyridine may be intensified upon preincubation of deprenyl with mitochondria in the presence of 4-ethylpyridine. The data obtained demonstrate the difference in the type and mechanism of inhibition of the deamination of serotonin by chlorgiline as well as in the type and mechanism of oxidation of beta-phenylethylamine by deprenyl. The possible mechanism of selective blocking of MAO activity by chlorgiline and deprenyl was discussed in terms of our previous data on the existence in the active center of mitochondrial MAO of specific sites for substrate binding, differing in their structure-functional characteristics.
研究了氯吉兰和司来吉兰对血清素（单胺氧化酶（MAO）A型的主要底物）脱氨基作用的抑制，以及大鼠肝线粒体膜片段对β-苯乙胺（MAO B型的主要底物）脱氨基作用的抑制，同时研究了4-乙基吡啶对该过程的影响。结果表明，当以血清素为底物时，线粒体膜片段的MAO活性对氯吉兰高度敏感；而当以β-苯乙胺为底物时，观察到其对司来吉兰高度敏感。4-乙基吡啶（5×10⁻³ M）是MAO活性的竞争性可逆抑制剂，分别抑制血清素和β-苯乙胺的脱氨基作用34%和30%。在用氯吉兰（MAO A型的特异性抑制剂）进行的实验中，在不同浓度氯吉兰（30分钟，23℃）预孵育线粒体后，向样品中加入4-乙基吡啶（5×10⁻³ M），可降低氯吉兰对β-苯乙胺脱氨基作用的抑制，但显著增强氯吉兰对血清素氧化的抑制作用。在类似的用司来吉兰（MAO B型的特异性抑制剂）进行的实验中，4-乙基吡啶（5×10⁻³ M）不仅降低了司来吉兰对血清素（MAO A的底物）脱氨基作用的抑制，还降低了其对β-苯乙胺（MAO B型的主要底物）氧化的抑制。在4-乙基吡啶存在下，司来吉兰与线粒体预孵育后，再加入4-乙基吡啶，司来吉兰对β-苯乙胺脱氨基作用的抑制作用降低可能会增强。所获得的数据证明了氯吉兰对血清素脱氨基作用的抑制类型和机制，以及司来吉兰对β-苯乙胺氧化的抑制类型和机制存在差异。根据我们之前关于线粒体MAO活性中心存在底物结合特定位点的研究数据，讨论了氯吉兰和司来吉兰选择性阻断MAO活性的可能机制，这些位点在结构功能特征上有所不同。
