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首页> 外文期刊>Biochemistry >Selective oxygenation ofhte endocannabinoid 2-Arachidonylglycerol by Leukocyte-Type 12-Lipoxygenase
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Selective oxygenation ofhte endocannabinoid 2-Arachidonylglycerol by Leukocyte-Type 12-Lipoxygenase

机译：白细胞型12-脂氧合酶对内源性大麻素2-花生四烯酸甘油的选择性氧化

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摘要

The endogenous cannabinoid system appears to serve vascular, neurological, immunological, and reproductive functions. The identification of 2-arachidonylglycerol (2-AG) as an endogenous ligand for the central (CB 1) and peripheral (CB2) cannabinoid receptors has prompted interest in enzymes capable of modifying or inactivating this endocannabinoid. Porcine leukocyte 12-liopoxygenase (12-LOX) oxygenated 2-AG to the 2-glyceryl ester of 12(S)-hydroperoxyeicosa-5,8,10,14-tetraenoic acid (12-HPETE- G). The kcat/KM for oxygenation of 2-AG was 40% of the value for arachidonic acid. In contrast to the results with leukocyte l2-LOX, 2-AG oxygenation was not detected with platelet-type l2-LOX. Among a series of structurally related arachidonyl esters, 2-AG served as the preferential substrate for leukocyte 12-LOX. 12(S)-Hydroxyeicosa-5,8,10,14-tetraenoic acid glyceryl ester (12-HETE-G) was produced following addition of 2-AG to COS- 7 cells transiently transfected with leukocyte 12-LOX. These results demonstrate that leukocyte-type 12-LOX efficiently oxidizes 2-AG in vitro and in intact cells, suggesting a role for this oxygenase in the endogenous cannabinoid system.
机译：内源性大麻素系统似乎具有血管，神经，免疫和生殖功能。将2-花生四烯酸甘油酯（2-AG）鉴定为中枢（CB 1）和外周（CB2）大麻素受体的内源性配体，已引起人们对能够修饰或灭活该内源大麻素的酶的兴趣。猪白细胞12-脂氧合酶（12-LOX）将2-AG氧化成12（S）-氢过氧叶酸5,8,10,14-四烯酸（12-HPETE-G）的2-甘油酯。 2-AG氧化的kcat / KM是花生四烯酸值的40％。与白细胞l2-LOX的结果相反，血小板型l2-LOX未检测到2-AG氧合。在一系列与结构相关的花生四烯酸酯中，2-AG作为白细胞12-LOX的优先底物。向白细胞12-LOX瞬时转染的COS-7细胞中添加2-AG后，产生了12（S）-羟基5,8,10,14-丁烯酸甘油酯（12-HETE-G）。这些结果表明，白细胞型12-LOX在体外和完整细胞中能有效氧化2-AG，表明该加氧酶在内源性大麻素系统中的作用。

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