SUBCELLULAR-LOCALIZATION OF CYTOCHROME-P450, AND ACTIVITIES OF SEVERAL ENZYMES RESPONSIBLE FOR DRUG-METABOLISM IN THE HUMAN BRAIN
SUBCELLULAR-LOCALIZATION OF CYTOCHROME-P450, AND ACTIVITIES OF SEVERAL ENZYMES RESPONSIBLE FOR DRUG-METABOLISM IN THE HUMAN BRAIN
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DOI：
10.1016/0006-2952(93)90139-n
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发表时间：
1993-02-09
影响因子：
5.8
通讯作者：
MINN, A
中科院分区：
文献类型：
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作者：
GHERSIEGEA, JF;PERRIN, R;MINN, A
我们研究了尸检时取出的人脑六个区域中细胞色素 P450 的亚细胞分布和相关单加氧酶活性。在所有研究区域中，线粒体部分中总细胞色素 P450 的含量比微粒体中的含量至少高九倍。然而，细胞色素 P450 依赖性酶活性（代表代谢外源分子的不同亚型）表现出微粒体的普遍性，这是先前在大鼠脑中观察到的情况。其他催化功能化和缀合反应的药物代谢酶在人脑中呈现出以下特征：（i）NADPH-细胞色素P450还原酶活性低，该酶也催化一些外源物质的还原； (ii)膜结合环氧化物水解酶的高比活性； (iii)在催化缀合反应的酶中，1-萘酚-UDP-葡萄糖醛酸基转移酶活性几乎检测不到或检测不到，而平均谷胱甘肽-S-转移酶活性比大鼠脑中测量的活性高15倍。人脑微血管中存在多种药物代谢酶活性，特别是环氧化物水解酶的高活性，表明这些酶参与代谢血脑屏障。
We studied the subcellular distribution of cytochrome P450 and related monooxygenase activities in six regions of human brains removed at autopsy. The content of total cytochrome P450 was found to be at least nine times higher in the mitochondrial fraction than in the microsomes in all the regions studied. However, cytochrome P450-dependent enzymatic activities which are representative of different isoforms metabolizing exogenous molecules exhibited a microsomal prevalence, a situation previously observed in rat brain. The other drug-metabolizing enzymes catalysing functionalization and conjugation reactions, presented the following characteristics in human brain: (i) a low activity of NADPH-cytochrome P450 reductase, which also catalyses the reduction of some xenobiotics; (ii) a high specific activity of the membrane-bound epoxide hydrolase; (iii) among the enzymes catalysing conjugation reactions, 1-naphthol-UDP-glucuronosyltransferase activity was barely or not detectable, whereas the mean glutathione-S-transferase activity was 15 times higher than the activity measured in rat brain. The presence of several drug-metabolizing enzyme activities in human brain microvessels, and particularly the high activity of epoxide hydrolase, suggests a participation of these enzymes in the metabolic blood-brain barrier.