Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases.
Comparison of the function and expression of CYP26A1 and CYP26B1, the two retinoic acid hydroxylases.
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两种视黄酸羟化酶 CYP26A1 和 CYP26B1 的功能和表达的比较。
DOI：
10.1016/j.bcp.2011.10.007
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发表时间：
2012
影响因子：
5.8
通讯作者：
Isoherranen,Nina
中科院分区：
文献类型：
--
作者：
Topletz,ArielR;Thatcher,JayneE;Zelter,Alex;Lutz,JustinD;Tay,Suzanne;Nelson,WendelL;Isoherranen,Nina
全反式视黄酸（atRA）是所有脊索动物中的重要信号分子。细胞色素 P450 酶 CYP26 被认为通过氧化代谢部分调节 atRA 的细胞浓度，从而影响类维生素A稳态和信号传导。 CYP26A1 和 CYP26B1 是 atRA 羟化酶，可催化细胞系统中类似代谢物的形成。然而，它们只有 40% 的序列相似性，表明两种酶之间存在差异。本研究的目的是确定 CYP26A1 和 CYP26B1 是否具有相似的催化活性、与 atRA 形成不同的代谢物以及在成人的不同组织中表达。 CYP26A1和CYP26B1的mRNA表达在除人小脑（其中CYP26B1是主要CYP26）和肝脏（其中CYP26A1占主导地位）之外的人体组织之间存在相关性。人体组织中 CYP26A1 和 CYP26B1 蛋白的定量与 mRNA 表达一致，并显示两种亚型之间的相关性。定性地，重组 CYP26A1 和 CYP26B1 从 atRA 形成相同的初级和连续代谢物。定量地，对于4-OH-RA的形成，CYP26B1具有比CYP26A1（Km=50nM和Vmax=10pmol/min/pmol）更低的Km（19nM）和Vmax（0.8pmol/min/pmol）。 atRA 的主要代谢物 4-OH-RA、18-OH-RA 和 4-oxo-RA 都是 CYP26A1 和 CYP26B1 的底物，CYP26A1 对所有测试底物的催化活性高出 2-10 倍。这项研究表明，CYP26A1 和 CYP26B1 是性质相似的 RA 羟化酶，具有重叠的表达谱。 CYP26A1 比 CYP26B1 具有更高的催化活性，并且似乎负责 atRA 在充当 atRA 暴露屏障的组织中的代谢。
All-trans-retinoic acid (atRA) is an important signaling molecule in all chordates. The cytochrome P450 enzymes CYP26 are believed to partially regulate cellular concentrations of atRA via oxidative metabolism and hence affect retinoid homeostasis and signaling. CYP26A1 and CYP26B1 are atRA hydroxylases that catalyze formation of similar metabolites in cell systems. However, they have only 40% sequence similarity suggesting differences between the two enzymes. The aim of this study was to determine whether CYP26A1 and CYP26B1 have similar catalytic activity, form different metabolites from atRA and are expressed in different tissues in adults. The mRNA expression of CYP26A1 and CYP26B1 correlated between human tissues except for human cerebellum in which CYP26B1 was the predominant CYP26 and liver in which CYP26A1 dominated. Quantification of CYP26A1 and CYP26B1 protein in human tissues was in agreement with the mRNA expression and showed correlation between the two isoforms. Qualitatively, recombinant CYP26A1 and CYP26B1 formed the same primary and sequential metabolites from atRA. Quantitatively, CYP26B1 had a lower Km(19nM) and Vmax(0.8pmol/min/pmol) than CYP26A1 (Km=50nM and Vmax=10pmol/min/pmol) for formation of 4-OH-RA. The major atRA metabolites 4-OH-RA, 18-OH-RA and 4-oxo-RA were all substrates of CYP26A1 and CYP26B1, and CYP26A1 had a 2–10-fold higher catalytic activity towards all substrates tested. This study shows that CYP26A1 and CYP26B1 are qualitatively similar RA hydroxylases with overlapping expression profiles. CYP26A1 has higher catalytic activity than CYP26B1 and seems to be responsible for metabolism of atRA in tissues that function as a barrier for atRA exposure.
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影响因子：
5.8
作者：
Lutz, Justin D.;Dixit, Vaishali;Yeung, Catherine K.;Dickmann, Leslie J.;Zelter, Alex;Thatcher, Jayne E.;Nelson, Wendel L.;Isoherranen, Nina
通讯作者：
Isoherranen, Nina
影响因子：
2.7
作者：
Masayuki Uehara;K. Yashiro;S. Mamiya;J. Nishino;P. Chambon;P. Dollé;Y. Sakai
通讯作者：
Masayuki Uehara;K. Yashiro;S. Mamiya;J. Nishino;P. Chambon;P. Dollé;Y. Sakai
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Fiorella,PD;Napoli,JL
通讯作者：
Napoli,JL
影响因子：
2.6
作者：
Abu-Abed, S;MacLean, G;Dollé, P
通讯作者：
Dollé, P
DOI：
10.1016/s0021-9258(18)83274-4
发表时间：
1989-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
A. Shen;Todd D. Porter;T. E. Wilson;Charles B. Kasper
通讯作者：
A. Shen;Todd D. Porter;T. E. Wilson;Charles B. Kasper