Functional differences in the cytochrome P450 1 family enzymes from zebrafish (Danio rerio) using heterologously expressed proteins.
Functional differences in the cytochrome P450 1 family enzymes from zebrafish (Danio rerio) using heterologously expressed proteins.
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DOI：
10.1016/j.abb.2010.06.018
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发表时间：
2010-10-01
影响因子：
3.9
通讯作者：
Wilson JY
中科院分区：
文献类型：
--
作者：
Scornaienchi ML;Thornton C;Willett KL;Wilson JY
哺乳动物细胞色素P4501(CYP1a)基因已被广泛研究，但在其他脊椎动物中，只有CYP1a基因的功能得到了较好的研究。我们用11种荧光底物和苯并[a]芘(BaP)测定了斑马鱼CyP1A、CyP1B1、CyP1C1、CyP1C2和CyP1D1蛋白的催化活性。间苯二酚底物7-乙氧基间苯二酚、7-甲氧基间苯二酚和7-苄氧基间苯二酚均能被除细胞色素P1D外的所有细胞色素PER1代谢。CYP1A代谢几乎所有被测试的底物，尽管非异丙酚底物的代谢速率通常低于以异丙酚为基础的底物。斑马鱼CYP1s不代谢7-苄氧基喹啉、3-[2-(N，N-diethyl-N-methylamino)ethyl]-7-methoxy-4-methylcoumarin)或7-甲氧基-4-(氨甲基)-香豆素。细胞色素P1B1和细胞色素P1C2的BaP代谢率最高。3-羟基苯并[BaP]是除细胞色素P450_1D_1外的主要代谢产物。CyP1a显示出广泛的特异性，并且几乎在所有底物中具有最高的代谢率。CYP1C1和CYP1C2具有相似的底物特异性。除BaP外，所有底物的活性都很低，且对BaP有不同的区域选择性，提示其功能可能与其他酶不同。
Mammalian cytochrome P4501 (CYP1) genes are well characterized, but in other vertebrates only the functions of CYP1A genes have been well studied. We determined the catalytic activity of zebrafish CYP1A, CYP1B1, CYP1C1, CYP1C2 and CYP1D1 proteins using 11 fluorometric substrates and benzo[a]pyrene (BaP). The resorufin-based substrates, 7-ethoxyresorufin, 7-methoxyresorufin, and 7-benzyloxyresorufin, were well metabolized by all CYP1s except CYP1D1. CYP1A metabolized nearly all substrates tested, although rates for non-resorufin substrates were typically lower than resorufin-based substrates. Zebrafish CYP1s did not metabolize 7-benzyloxyquinoline, 3-[2-(N,N-diethyl-N-methylamino)ethyl]-7-methoxy-4-methylcoumarin or 7-methoxy-4-(aminomethyl)-coumarin. CYP1B1 and CYP1C2 had the highest rates of BaP metabolism. 3-hydroxy-BaP was a prominent metabolite for all but CYP1D1. CYP1A showed broad specificity and had the highest metabolic rates for nearly all substrates. CYP1C1 and CYP1C2 had similar substrate specificity. CYP1D1 had very low activities for all substrates except BaP, and a different regioselectivity for BaP, suggesting that CYP1D1 function may be different from other CYP1s.
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影响因子：
5.8
作者：
Nebert, DW;Roe, AL;Dalton, TP
通讯作者：
Dalton, TP
影响因子：
3.9
作者：
Goldstone, J. V.;Joensson, M. E.;Behrendt, L.;Woodin, B. R.;Jenny, M. J.;Nelson, D. R.;Stegeman, J. J.
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Stegeman, J. J.
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8.8
作者：
Parente, TEM;De-Oliveira, ACAX;Paumgartten, FJR
通讯作者：
Paumgartten, FJR
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4.1
作者：
Hegelund, T;Ottosson, K;Celander, MC
通讯作者：
Celander, MC