Institute for Molecular and Translational Therapeutic Strategies, Hannover Medical School, Hannover, Germany.
Liver Int. 2010 Sep;30(8):1181-8. doi: 10.1111/j.1478-3231.2010.02310.x. Epub 2010 Jul 8.
Oleic acid is a major systemically circulating fatty acid in humans with atheroprotective and immunomodulatory properties. As of today, the contribution of individual cytochrome P450 (CYP) mono-oxygenases to the epoxidation of this fatty acid is unknown. Furthermore, the extent of the oleic acid oxidation product cis-9,10-epoxyoctadecanoic acid (cis-EODA) in humans and its plasma levels in patients with impaired liver function are not known.
We studied cis-EODA in plasma of patients suffering from chronic liver diseases, a condition that often displays impaired liver CYP enzyme activities. Fifteen CYP mono-oxygenases were investigated in vitro as a potential source of cis-EODA.
Strikingly, plasma levels of cis-EODA were significantly repressed (P<0.0005) when patients with liver impairment (n=16) were compared with healthy subjects (n=14). Production of cis-EODA was catalysed by CYP in the following order: 2C8, 2C9, 2C19, 3A4, 1A2 and CYP3A7.
cis-EODA plasma concentrations are decreased in hepatic disease with impaired liver function. Oleic acid is primarily oxidized to oleic acid oxide (cis-EODA) by CYP2C and CYP3A mono-oxygenases. The liver is the major organ responsible for the oxidation of oleic acid to cis-EODA, and thus, cis-EODA may be a suitable biomarker to assess liver function.
油酸是人体内主要的循环脂肪酸，具有抗动脉粥样硬化和免疫调节作用。截至目前，尚不清楚个体细胞色素 P450（CYP）单加氧酶在这种脂肪酸环氧化中的作用。此外，尚不清楚人类油酸氧化产物顺-9,10-环氧十八烷酸（cis-EODA）的程度及其在肝功能受损患者中的血浆水平。
我们研究了慢性肝病患者血浆中的 cis-EODA，这种疾病通常表现出肝 CYP 酶活性受损。我们在体外研究了 15 种 CYP 单加氧酶，作为 cis-EODA 的潜在来源。
令人惊讶的是，与健康受试者（n=14）相比，肝功能受损的患者（n=16）的 cis-EODA 血浆水平显著降低（P<0.0005）。cis-EODA 的产生由 CYP 以以下顺序催化：2C8、2C9、2C19、3A4、1A2 和 CYP3A7。
cis-EODA 血浆浓度在肝功能受损的肝脏疾病中降低。油酸主要由 CYP2C 和 CYP3A 单加氧酶氧化为油酸氧化物（cis-EODA）。肝脏是氧化油酸生成 cis-EODA 的主要器官，因此，cis-EODA 可能是评估肝功能的合适生物标志物。
