叠氮化抑制人类细胞色素P -4502 e1, 1 a2和3 a4。

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Salmela KS, Tsyrlov IB,利CS

叠氮化抑制人类细胞色素P -4502 e1, 1 a2和3 a4。

酒精实验研究杂志2001年2月,25 (2):253 - 60。

PubMed ID

11236840 (在PubMed

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文摘

背景:最近,我们表明,除了细胞色素p - 4502 e1 (CYP2E1)、CYP1A2和CYP3A4也有助于微粒体乙醇氧化系统(meo)。当meo活动测量时,叠氮化钠通常用于阻止污染的过氧化氢酶。然而,尽管CYP2E1被认为是对叠氮化,其对其他影响p - 450 s是未知的。因此,本研究的目的是确定叠氮化的效果对人类重组和肝CYP2E1 CYP1A2和CYP3A4。方法和结果:叠氮化钠的浓度低至0.1毫米明显抑制特定的乙醇氧化(平均+ / - SEM)表达的重组CYP1A2和CYP3A4 HepG2细胞(16 + / - 1%和22 + / - 2%的控制没有叠氮化,分别;p < 0.01)。相比之下,CYP2E1的具体活动仅略(而不是显著)抑制叠氮化在这个浓度(79 + / - 12%的控制)。同样,在人类肝微粒体(n = 6), 0.1毫米叠氮化强烈抑制CYP1A2-dependent(25 + / - 2%)和CYP3A4-dependent(15 + / - 2%)乙醇氧化,而CYP2E1是抑制叠氮化只在10毫米(60 + / - 10%)。叠氮化也强烈影响的明显动能值三个同功酶。此外,叠氮化抑制特定的单氧酶活动,通过重组和微粒体p - 450。 CYP2E1-specific p-nitrophenol hydroxylation was the most sensitive to azide, whereas CYP1A2-dependent 7-methoxyresorufin O-dealkylation was only slightly inhibited. Judging from its effect on p-nitrophenol hydroxylation by human liver microsomes, the inhibition of azide was competitive (Ki 0.09 mM). CONCLUSIONS: Sodium azide at a concentration as low as 0.1 mM inhibited ethanol oxidation by CYP1A2 and CYP3A4. With CYP2E1, although oxidation of 50 mM ethanol was not inhibited by 0.1 mM azide, higher azide concentrations were inhibitory and 0.1 mM azide seemed to affect the kinetics of ethanol oxidation by CYP2E1. Therefore, azide should be avoided when measuring the MEOS activity because it may lead to underestimation, especially of CYP1A2- and CYP3A4-dependent ethanol oxidation.

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药物酶

药物	酶	类	生物	药理作用	行动
乙醇	细胞色素P450 1 a2	蛋白质	人类	未知的	底物	细节
乙醇	细胞色素P450 3 a4	蛋白质	人类	未知的	底物 抑制剂 诱导物	细节