肿瘤特异性人类细胞色素P450 CYP2W1对内源性底物的催化活性
Catalytic Activities of Tumor-Specific Human Cytochrome P450 CYP2W1 Toward Endogenous Substrates.
作者信息
Zhao Yan, Wan Debin, Yang Jun, Hammock Bruce D, Ortiz de Montellano Paul R
机构信息
Department of Pharmaceutical Chemistry, University of California, San Francisco (Y.Z., P.R.O.M.) and Department of Entomology and Cancer Center, University of California, Davis, CA (D.W., J.Y., B.D.H.).
Department of Pharmaceutical Chemistry, University of California, San Francisco (Y.Z., P.R.O.M.) and Department of Entomology and Cancer Center, University of California, Davis, CA (D.W., J.Y., B.D.H.)
出版信息
Drug Metab Dispos. 2016 May;44(5):771-80. doi: 10.1124/dmd.116.069633. Epub 2016 Mar 2.
CYP2W1 is a recently discovered human cytochrome P450 enzyme with a distinctive tumor-specific expression pattern. We show here that CYP2W1 exhibits tight binding affinities for retinoids, which have low nanomolar binding constants, and much poorer binding constants in the micromolar range for four other ligands. CYP2W1 converts all-transretinoic acid (atRA) to 4-hydroxyatRA and all-transretinol to 4-OH all-transretinol, and it also oxidizes retinal. The enzyme much less efficiently oxidizes 17β-estradiol to 2-hydroxy-(17β)-estradiol and farnesol to a monohydroxylated product; arachidonic acid is, at best, a negligible substrate. These findings indicate that CYP2W1 probably plays an important role in localized retinoid metabolism that may be intimately linked to its involvement in tumor development.
CYP2W1是一种最近发现的人类细胞色素P450酶，具有独特的肿瘤特异性表达模式。我们在此表明，CYP2W1对类视黄醇表现出紧密的结合亲和力，其结合常数在低纳摩尔范围，而对其他四种配体的结合常数在微摩尔范围则要低得多。CYP2W1将全反式维甲酸（atRA）转化为4-羟基atRA，将全反式视黄醇转化为4-OH全反式视黄醇，并且它还氧化视黄醛。该酶将17β-雌二醇氧化为2-羟基-（17β）-雌二醇以及将法尼醇氧化为单羟基化产物的效率要低得多；花生四烯酸充其量只是一种可忽略不计的底物。这些发现表明，CYP2W1可能在局部类视黄醇代谢中发挥重要作用，这可能与其参与肿瘤发展密切相关。
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