肝脏分解代谢的作用人类CYP4F2促炎代理白三烯B4。
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金R, Koop博士,Raucy杰,拉斯科JM
肝脏分解代谢的作用人类CYP4F2促炎代理白三烯B4。
拱生物化学Biophys。1998年11月1日,359 (1):89 - 98。
- PubMed ID
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9799565 (在PubMed]
- 文摘
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白三烯B4 (LTB4),一个花生四烯酸衍生物,是一种有效的促炎剂终止了他的行动通过微粒体omega-hydroxylation分解代谢途径。尽管肝脏作为主要网站从体循环LTB4间隙,肝LTB4新陈代谢疾病定义的属性。因此,我们研究了新陈代谢的LTB4 omega-hydroxylated代谢物20-hydroxyleukotriene B4 (20-OH LTB4)由人类肝脏微粒体并纯化肝P450酶潜在的反应。肝微粒体从10个不同的主题转换LTB4 20-OH LTB4相似率(1.06 + / - 0.3 nmol /分钟/ nmol P450酶;0.25 + / - 0.1 nmol /分钟/毫克蛋白)。微粒体的分析LTB4 20-hydroxylation反应显示动力学参数(明显的74.8公里的microM VMAX 2.42 nmol /分钟/ nmol P450)与由单一P450酶催化一致。传统色谱法结合免疫化学筛选与鼠CYP4A1抗体被用来隔离从人类肝脏微粒体P450酶分子量为57000和一个NH2-terminal氨基酸序列有94%同源(12 trp - - > 12 g)在第一个17残留与人类CYP4F2 cDNA-derived序列。在调整P450还原酶和磷脂,CYP4F2 LTB4转化成20-OH LTB4的流动率392 pmol /分钟/ nmol P450,而其他人类肝脏P450测试,包括CYP4A11,但在展出LTB4 omega-hydroxylase活动。多克隆抗体CYP4F2被发现明显抑制(91.9 + / - 5%;n = 5) LTB4 20-hydroxylation由人类肝脏微粒体。 Microsomal 20-OH LTB4 formation was also inhibited 30% by arachidonic acid, a known CYP4F2 substrate, and 50% by prostaglandin A1 but was unaffected by lauric acid, palmitic acid, and PGF2alpha. Finally, a strong correlation (r = 0.86; P < 0.002; n = 10) was observed between CYP4F2 content and LTB4 20-hydroxylase activity in the human liver samples. Our results indicate that CYP4F2 is the principle LTB4 omega-hydroxylating enzyme expressed in human liver and, as such, may play an important role in regulating circulating as well as hepatic levels of this powerful proinflammatory eicosanoid.