Positional specificity of rabbit CYP4B1 for ω-hydroxylation of short-medium chain fatty acids and hydrocarbons
Positional specificity of rabbit CYP4B1 for ω-hydroxylation of short-medium chain fatty acids and hydrocarbons
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DOI：
10.1006/bbrc.1998.8842
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发表时间：
1998-07-20
影响因子：
3.1
通讯作者：
Rettie, AE
中科院分区：
文献类型：
--
作者：
Fisher, MB;Zheng, YM;Rettie, AE
将兔细胞色素P4B1与一系列脂肪酸和碳氢化合物底物孵育，用气相色谱和气相色谱/质谱仪鉴定代谢产物。C-7到C-10正构烷基脂肪酸优先在末端碳(omega/omega-1=1.1-7.4)上羟基化，其翻转次数为1-11min(-1)。对于相应的反应，C-7到C-10正构烷基烃的翻转数为11-33min(-1)，在热力学上不利的位置(omega/omega-1=1.6-23)进行羟化反应的区域选择性更高。这些结果证明了细胞色素P4B1和其他细胞色素P4脂肪酸羟基酶之间的功能联系，并进一步表明细胞色素P4B1的S不寻常的位置特异性不是由底物上存在的羧酸盐(或极性)锚定决定的。这表明存在一个主要的烃结合部位，它有效地限制了中短链烷基底物对兔CYP4B1活性部位上的高铁物种的访问。(C)1998年学术出版社。
Rabbit CYP4B1 was incubated with a series of fatty acid and hydrocarbon substrates and metabolites were identified by gas chromatography and gas chromatography/mass spectrometry. C-7 to C-10 n-alkyl fatty acids were preferentially hydroxylated at the terminal carbon (omega/omega-1 = 1.1-7.4) with turnover numbers of 1-11 min(-1). The C-7 to C-10 n-alkyl hydrocarbons exhibited turnover numbers of 11-33 min(-1) for the corresponding reactions and even higher regioselectivities for hydroxylation at the thermodynamically disfavored site (omega/omega-1 = 1.6-23). These results demonstrate a functional link between CYP4B1 and other CYP4 fatty acid hydroxylases, and show further that CYP4B1's unusual positional specificity is not dictated by the presence of a carboxylate (or polar) anchor on the substrate. This suggests the presence of a dominant hydrocarbon binding site which effectively restricts the access of short-medium chain n-alkyl substrates to the perferryl species in the active site of rabbit CYP4B1. (C) 1998 Academic Press.