6 alpha-hydroxylation taurochenodeoxycholic酸和CYP3A4石胆酸的人类肝脏微粒体。

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阿瑞亚Z, Wikvall K

6 alpha-hydroxylation taurochenodeoxycholic酸和CYP3A4石胆酸的人类肝脏微粒体。

Biochim Biophys学报。1999年4月19日,1438 (1):47-54。

PubMed ID

10216279 (在PubMed

]

文摘

本研究的目的是确定酶在人类肝脏胆汁酸的催化羟基化。十四重组表达的细胞色素P450 (CYP)酶,人类从不同的捐赠者,肝微粒体和选择性细胞色素P450抑制剂被用来研究taurochenodeoxycholic酸的羟基化和石胆酸。重组表达CYP3A4酶是唯一主动向这些胆汁酸和酶催化的有效6 alpha-hydroxylation taurochenodeoxycholic酸和石胆酸。6 alpha-hydroxylation taurochenodeoxycholic酸的Vmax CYP3A4 18.2 nmol / nmol P450公里90 microM /分钟和明显。细胞色素b5最大活动的需要。人类的肝脏微粒体从10个不同的捐赠者,不同的P450标记活动已经确定,分别孵化taurochenodeoxycholic酸和石胆酸。很强的相关性被发现之间的6 alpha-hydroxylation taurochenodeoxycholic酸,CYP3A水平(r2 = 0.97)和睾酮6 beta-hydroxylation (r2 = 0.9)。也有很强的相关性之间的6 alpha-hydroxylation石胆酸,CYP3A水平和睾丸激素6 beta-hydroxylation (r2 = 0.7)。Troleandomycin CYP3A酶的选择性抑制剂,抑制6 alpha-hydroxylation taurochenodeoxycholic酸几乎完全在一个10 microM浓度。其他抑制剂,如alpha-naphthoflavone sulfaphenazole和强内心百乐明很少或没有影响的活动。 The apparent Km for 6alpha-hydroxylation of taurochenodeoxycholic by human liver microsomes was high (716 microM). This might give an explanation for the limited formation of 6alpha-hydroxylated bile acids in healthy humans. From the present results, it can be concluded that CYP3A4 is active in the 6alpha-hydroxylation of both taurochenodeoxycholic acid and lithocholic acid in human liver.

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药物酶

药物	酶	类	生物	药理作用	行动
Taurochenodeoxycholic酸	细胞色素P450 3 a4	蛋白质	人类	未知的	底物	细节