New players in the fatty acyl ethanolamide metabolism
New players in the fatty acyl ethanolamide metabolism
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脂肪酰乙醇酰胺代谢的新参与者
DOI：
10.1016/j.phrs.2014.04.001
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发表时间：
2014
影响因子：
9.3
通讯作者：
et al.
中科院分区：
文献类型：
--
作者：
Iffat Ara Sonia Rahman;et al.
脂肪酰基乙醇酰胺是一类具有生物活性的内源性脂质分子，通常称为N-酰基乙醇胺（NAE）。NAE包括棕榈酰乙醇胺（抗炎和镇痛物质）、油酰乙醇胺（镇痛物质）和大麻素（内源性大麻素）。NAE的内源水平主要由负责其生物合成和降解的酶调节。在哺乳动物组织中，主要的生物合成途径从甘油磷脂开始，由两个酶反应组成。第一步是钙离子依赖的N-酰基转移酶催化的乙醇胺磷脂的N-酰化，第二步是N-酰基磷脂酰乙醇胺（NAPE）水解磷脂酶D（NAPE-PLD）从N-酰化的乙醇胺磷脂中释放NAE。脂肪酸酰胺水解酶在NAEs的降解中起着核心作用。然而，最近的研究强烈表明其他酶参与NAE代谢。这些酶包括HRAS样抑制因子家族的成员（也称为磷脂酶A/酰基转移酶家族），其最初被发现作为肿瘤抑制剂，但可以作为Ca 2+非依赖性NAPE形成N-酰基转移酶发挥作用;参与NAPE-PLD非依赖性多步途径以从NAPE产生NAE的多种酶，这通过对NAPE-PLD缺陷小鼠的分析而被发现;和作为第二NAE水解酶的溶酶体NAE水解酸性酰胺酶。这些新发现的酶可能成为开发新的治疗药物的靶点。在这里，我们集中在这一领域的最新酶学研究结果。
Fatty acyl ethanolamides represent a class of endogenous bioactive lipid molecules and are generally referred to asN-acylethanolamines (NAEs). NAEs include palmitoylethanolamide (anti-inflammatory and analgesic substance), oleoylethanolamide (anorexic substance), and anandamide (endocannabinoid). The endogenous levels of NAEs are mainly regulated by enzymes responsible for their biosynthesis and degradation. In mammalian tissues, the major biosynthetic pathway starts from glycerophospholipids and is composed of two enzyme reactions. The first step isN-acylation of ethanolamine phospholipids catalyzed by Ca2+-dependentN-acyltransferase and the second step is the release of NAEs fromN-acylated ethanolamine phospholipids byN-acylphosphatidylethanolamine (NAPE)-hydrolyzing phospholipase D (NAPE-PLD). As for the degradation of NAEs, fatty acid amide hydrolase plays the central role. However, recent studies strongly suggest the involvement of other enzymes in the NAE metabolism. These enzymes include members of the HRAS-like suppressor family (also called phospholipase A/acyltransferase family), which were originally discovered as tumor suppressors but can function as Ca2+-independent NAPE-formingN-acyltransferases; multiple enzymes involved in the NAPE-PLD-independent multi-step pathways to generate NAE from NAPE, which came to light by the analysis of NAPE-PLD-deficient mice; and a lysosomal NAE-hydrolyzing acid amidase as a second NAE hydrolase. These newly recognized enzymes may become the targets for the development of new therapeutic drugs. Here, we focus on recent enzymological findings in this area.