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对PGH合酶抑制剂的研究,其效力受酶的氧化还原状态调节。

Study of inhibitors of the PGH synthases for which potency is regulated by the redox state of the enzymes.

作者信息

Boutaud Olivier, Oates John A

机构信息

Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.

出版信息

Methods Mol Biol. 2010;644:67-90. doi: 10.1007/978-1-59745-364-6_7.

DOI:10.1007/978-1-59745-364-6_7
PMID:20645166
Abstract

Aspirin, salicylic acid, and acetaminophen are examples of drugs that inhibit the PGH synthases (cyclooxygenases) with potencies that vary remarkably between different cells. This results from the fact that the inhibitory action of these drugs is regulated by redox cycling of the enzymes, which is determined by the concentration of hydroperoxides in the enzyme proximity. The potency of these drugs is greatest in the presence of low concentrations of hydroperoxides. Accordingly, analysis of the action of these inhibitors requires consideration of assay conditions that take into account the factors that control hydroperoxide concentrations, both in studies with purified enzymes and in cells.

摘要

阿司匹林、水杨酸和对乙酰氨基酚是抑制PGH合酶(环氧化酶)的药物示例,其在不同细胞中的效力差异显著。这是因为这些药物的抑制作用受酶的氧化还原循环调节,而氧化还原循环由酶附近的氢过氧化物浓度决定。在低浓度氢过氧化物存在的情况下,这些药物的效力最大。因此,在对纯化酶和细胞进行研究时,分析这些抑制剂的作用需要考虑能够控制氢过氧化物浓度的检测条件。

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