Lipidomic metabolism analysis of the endogenous cannabinoid anandamide (N-arachidonylethanolamide).
Lipidomic metabolism analysis of the endogenous cannabinoid anandamide (N-arachidonylethanolamide).
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内源性大麻素 anandamide（N-花生四烯乙醇酰胺）的脂质代谢分析。
DOI：
10.1016/j.jpba.2010.03.035
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发表时间：
2010
影响因子：
3.4
通讯作者：
Barker,EricL
中科院分区：
文献类型：
--
作者：
Placzek,EkaterinaA;Cooper,BruceR;Placzek,AndrewT;Chester,JuliaA;Davisson,VJo;Barker,EricL
与脂质代谢相关的途径的阐明受到与检测和结构鉴定相关的分析挑战的限制。基于发现的质谱脂质组学方法已被应用于鉴定内源性大麻素anandamide（N-花生四烯乙醇酰胺）的代谢产物。以前，建立了一个模型系统，表明大麻素可以被细胞回收，形成新的内源性大麻素，表明花生四烯酸碳链的回收。我们假设存在不同的细胞途径来指导花生四烯酸衍生的花生四烯酸链进入一组特定的代谢物，不同于由非花生四烯酸衍生的花生四烯酸组成的代谢物库。使用稳定同位素编码和液相色谱-质谱法，我们确定了一个独特的池来自外源花生四烯酸或花生四烯酸在RBL-2 H3细胞的脂质代谢产物。我们发现，花生四烯酸衍生的代谢物主要由类花生酸脂质类组成，而花生四烯酸衍生的花生四烯酸，除了类花生酸，被代谢成diradylglycerols，脂肪酸酰胺，甾醇，和甘油磷脂。特别感兴趣的花生四烯酸酰胺代谢物列表中有1-O-花生四烯酸-sn-甘油-3-磷酸胆碱。此外，我们确定，虽然1-O-花生四烯酸-sn-甘油-3-磷酸胆碱可能是花生四烯酸的代谢产物，但sn-2化合物在小鼠脑组织中更丰富。总的来说，我们的研究结果提供了一种新的方法来研究内源性大麻素和脂肪酸衍生的信号分子的代谢命运。
Elucidation of pathways involved with lipid metabolism has been limited by analytical challenges associated with detection and structure identification. A discovery-based mass spectrometry lipidomic approach has been applied to identify metabolites of the endogenous cannabinoid anandamide (N-arachidonylethanolamide). Previously, a model system was established to show that anandamide can be recycled by cells to form new endocannabinoids suggesting recycling of the arachidonate carbon chain. We hypothesized that distinct cellular pathways exist to direct the anandamide-derived arachidonate chain into a specific set of metabolites, different from the metabolite pool that is comprised of non-anandamide-derived arachidonic acid. Using stable isotope encoding and liquid chromatography–mass spectrometry, we identified a distinct pool of lipid metabolites derived from exogenous anandamide or arachidonic acid in RBL-2H3 cells. We discovered that arachidonic acid-derived metabolites were primarily comprised of the eicosanoid lipid class, whereas anandamide-derived arachidonic acid, in addition to eicosanoids, was metabolized into diradylglycerols, fatty acid amides, sterols, and glycerophospholipids. From the list of anandamide metabolites of particular interest was 1-O-arachidonyl-sn-glycero-3-phosphocholine. Furthermore, we determined that while 1-O-arachidonyl-sn-glycero-3-phosphocholine may be a metabolite of anandamide, the sn-2 compound was more abundant in mouse brain tissue. Overall, our results provide a novel approach to study the metabolic fate of endocannabinoids and fatty acid-derived signaling molecules.