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人类脑苯酚磺基转移酶:生化特性与区域定位

Human brain phenol sulfotransferase: biochemical properties and regional localization.

作者信息

Young W F, Okazaki H, Laws E R, Weinshilboum R M

出版信息

J Neurochem. 1984 Sep;43(3):706-15. doi: 10.1111/j.1471-4159.1984.tb12790.x.

Abstract

Phenol sulfotransferase (PST) catalyzes the sulfate conjugation of catecholamines and phenol and catechol drugs. The human blood platelet contains a thermolabile (TL) form of PST that catalyzes the sulfate conjugation of dopamine and other monoamines and a thermostable (TS) form that catalyzes the sulfate conjugation of micromolar concentrations of phenol and p-nitrophenol. Experiments were performed to determine whether the brain contains forms of PST analogous to the TL and TS forms found in the human platelet, and to determine whether there are regional variations in human brain PST activity. We found that the human brain contains at least two forms of PST, forms that are similar to the platelet TS and TL forms of the enzyme with respect to substrate specificity, apparent Km constants, thermal stability, and sensitivity to inhibitors. Optimal conditions were determined for the measurement of these two activities in brain homogenates. The stability of PST activities in the human brain after death was determined in five samples of cerebral cortex that were obtained during clinically indicated neurosurgical procedures. An average of 76 +/- 8% and 80 +/- 9% (mean +/- SEM) of the basal TL and TS PST activities, respectively, remained in these five samples of cerebral cortex after 8 h of storage under simulated post-mortem conditions. Six human brains were then obtained less that 8 h after death from patients who had no neurological disease prior to death. The mean activities of the TL and TS forms of PST were measured in 17 different regions of the six brains. If the pituitary was excluded from consideration, TL and TS PST activities both varied approximately fivefold among these regions, and both activities were highest in cerebral cortex. However, the average TS activity in the anterior pituitary, a tissue of non-neural origin embryologically, was 6.5-fold greater than the highest average TS PST activity found in cerebral cortex.

摘要

苯酚磺基转移酶(PST)催化儿茶酚胺、苯酚和儿茶酚类药物的硫酸结合反应。人血小板中含有一种热不稳定(TL)形式的PST,它催化多巴胺和其他单胺的硫酸结合反应;还含有一种热稳定(TS)形式的PST,它催化微摩尔浓度的苯酚和对硝基苯酚的硫酸结合反应。开展实验以确定大脑中是否存在类似于人血小板中发现的TL和TS形式的PST,以及确定人脑中PST活性是否存在区域差异。我们发现,人脑中至少含有两种形式的PST,这两种形式在底物特异性、表观米氏常数、热稳定性以及对抑制剂的敏感性方面类似于血小板中该酶的TS和TL形式。确定了在脑匀浆中测量这两种活性的最佳条件。在临床指示的神经外科手术过程中获取的5份大脑皮质样本中,测定了死后人类大脑中PST活性的稳定性。在模拟死后条件下储存8小时后,这5份大脑皮质样本中,基础TL和TS PST活性分别平均保留了76±8%和80±9%(平均值±标准误)。然后从生前无神经系统疾病的患者中获取了6个人脑,死亡后不到8小时。在这6个人脑的17个不同区域中测量了PST的TL和TS形式的平均活性。如果不考虑垂体,在这些区域中,TL和TS PST活性均大约相差5倍,且两种活性在大脑皮质中最高。然而,垂体前叶(一种胚胎学上非神经起源的组织)中的平均TS活性比大脑皮质中发现的最高平均TS PST活性高6.5倍。

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