Biosynthetic pathways of bioactive N-acylethanolamines in brain.
Biosynthetic pathways of bioactive N-acylethanolamines in brain.
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DOI：
10.2174/1871527311312010005
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发表时间：
2013-01
期刊：
影响因子：
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通讯作者：
K. Tsuboi;Natsuki Ikematsu;T. Uyama;D. Deutsch;A. Tokumura;N. Ueda
中科院分区：
文献类型：
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作者：
K. Tsuboi;Natsuki Ikematsu;T. Uyama;D. Deutsch;A. Tokumura;N. Ueda
长链脂肪酸的乙醇酰胺是一类内源性脂质介质，通常称为N酰基乙醇胺（NAE）。NAE包括抗炎和镇痛的棕榈酰乙醇胺、棕榈油酰乙醇胺和内源性大麻素anandamide。由于NAE的内源性水平主要由负责其生物合成和降解的酶调节，因此这些酶有望成为开发治疗剂的靶点。因此，更好地了解这些酶是必不可少的。NAE生物合成的经典“N-酰化磷酸二酯酶途径”包括两个步骤：N-酰基转移酶生成N-酰基磷脂酰乙醇胺（NAPE）和NAPE水解磷脂酶D（NAPE-PLD）从NAPE中释放NAE。然而，最近的研究，包括NAPE-PLD-缺陷（NAPE-PLD-/-）小鼠的分析，揭示了NAPE-PLD-独立的多步途径的存在，以形成NAE从NAPE在动物组织中。我们最近使用NAPE-PLD-/-小鼠的研究还表明，NAE不仅由NAPE形成，而且还通过NAPE-PLD依赖性和非依赖性途径由N-酰基-缩醛磷脂型乙醇胺磷脂（N-酰基-缩醛磷脂酰乙醇胺）形成。在这里，我们提出了最近的研究结果NAE生物合成途径主要发生在大脑中。
Ethanolamides of long-chain fatty acids are a class of endogenous lipid mediators generally referred to as Nacylethanolamines (NAEs). NAEs include anti-inflammatory and analgesic palmitoylethanolamide, anorexic oleoylethanolamide, and the endocannabinoid anandamide. Since the endogenous levels of NAEs are principally regulated by enzymes responsible for their biosynthesis and degradation, these enzymes are expected as targets for the development of therapeutic agents. Thus, a better understanding of these enzymes is indispensable. The classic "N-acylationphosphodiesterase pathway" for NAE biosynthesis is composed of two steps; the formation of Nacylphosphatidylethanolamine (NAPE) by N-acyltransferase and the release of NAE from NAPE by NAPE-hydrolyzing phospholipase D (NAPE-PLD). However, recent studies, including the analysis of NAPE-PLD-deficient (NAPE-PLD-/-) mice, revealed the presence of NAPE-PLD-independent multi-step pathways to form NAEs from NAPE in animal tissues. Our recent studies using NAPE-PLD-/- mice also suggest that NAE is formed not only from NAPE, but also from Nacylated plasmalogen-type ethanolamine phospholipid (N-acyl-plasmenylethanolamine) through both NAPE-PLDdependent and -independent pathways. Here, we present recent findings on NAE biosynthetic pathways mainly occurring in the brain.