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半胱氨酸对多巴胺-β-羟化酶不可逆抑制作用的进一步研究

Further studies on irreversible inhibition of dopamine-beta-hydroxylase by cysteine.

作者信息

Izumi H, Hayakari M, Ozawa H

出版信息

Tohoku J Exp Med. 1976 Apr;118(4):373-80. doi: 10.1620/tjem.118.373.

Abstract

In the process of studying the inhibition of dopamine-beta-hydroxylase by cysteine, we observed an interesting relationship between cysteine and catalase. This suggests that two different patterns of the inhibition of dopamine-beta-hydroxylase exist; the one is reversible inhibition, the other is irreversible inhibition. In the present experiments, we have particularly investigated the irreversible inhibition of dopamine-beta-hydroxylase by cysteine, and the following conclusions were drawn: (a) The rate of the inhibitory effect of cysteine pretreatment on dopamine-beta-hydroxylase is independent of a function of the temperature, while at temperature above 20 degrees C the extent of the reversibility of cysteine inhibition by N-ethylmaleimide is temperature dependent. (b) The rate of inhibitory effect is dependent on the time of cysteine pretreatment at 37 degrees C, and the ability of N-ethylmaleimide to reverse the cystine-induced inhibition is gradually diminished by increasing the time of cysteine pretreatment. (c) The inhibitory effect of cysteine pretreatment (37 degrees C, 10 min) is not reversed by the addition of Cu++. (d) In the presence of higher concentrations of catalase, the cystein-induced inhibition is recovered after the addition of equimolar concentration of N-ethylmaleimide. (e) Both inhibitions of cysteine on dopamine-beta-hydroxylase with and without pretreatment were the noncompetitive type to the substrate, tyramine.

摘要

在研究半胱氨酸对多巴胺-β-羟化酶的抑制作用过程中,我们观察到半胱氨酸与过氧化氢酶之间存在一种有趣的关系。这表明存在两种不同模式的多巴胺-β-羟化酶抑制作用;一种是可逆抑制,另一种是不可逆抑制。在本实验中,我们特别研究了半胱氨酸对多巴胺-β-羟化酶的不可逆抑制作用,并得出以下结论:(a) 半胱氨酸预处理对多巴胺-β-羟化酶的抑制作用速率与温度无关,而在20℃以上温度时,N-乙基马来酰亚胺对半胱氨酸抑制作用的可逆程度与温度有关。(b) 抑制作用速率取决于37℃下半胱氨酸预处理的时间,并且随着半胱氨酸预处理时间的增加,N-乙基马来酰亚胺逆转胱氨酸诱导抑制作用的能力逐渐减弱。(c) 添加Cu++不能逆转半胱氨酸预处理(37℃,10分钟)的抑制作用。(d) 在存在较高浓度过氧化氢酶的情况下,添加等摩尔浓度的N-乙基马来酰亚胺后,半胱氨酸诱导的抑制作用得以恢复。(e) 无论有无预处理,半胱氨酸对多巴胺-β-羟化酶的两种抑制作用对底物酪胺均为非竞争性类型。

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