Lysophospholipid Acyltransferases and Arachidonate Recycling in Human Neutrophils
Lysophospholipid Acyltransferases and Arachidonate Recycling in Human Neutrophils
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DOI：
10.1074/jbc.m806194200
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发表时间：
2008-10-31
影响因子：
4.8
通讯作者：
Voelker, Dennis R.
中科院分区：
文献类型：
--
作者：
Gijon, Miguel A.;Riekhof, Wayne R.;Voelker, Dennis R.
磷脂的去酰化和再酰化循环在调节花生四烯酸在类二十烷生产中的可用性方面起着关键作用。酵母溶血磷脂酰基转移酶Ale1p与哺乳动物膜结合o -酰基转移酶（MBOAT）蛋白有关。我们在酵母菌中表达了四种人mboat，并使用基于质谱的新型酶分析研究了它们的酰基辅酶a和溶血磷脂特异性。MBOAT1是一种溶血磷脂酰丝氨酸（lyso-PS）酰基转移酶，偏爱油酰辅酶a。MBOAT2也倾向于油酰辅酶a，使用溶血磷脂酸和溶血磷脂酰乙醇胺作为酰基受体。MBOAT5倾向于溶血磷脂酰胆碱和溶血磷脂酰ps结合亚油基和花生四烯酰基链。MBOAT7是一种溶血磷脂酰肌醇酰基转移酶，对花生四烯酰基辅酶a具有显著的特异性。MBOAT5和MBOAT7特别容易受到硫柳汞的抑制。人类中性粒细胞表达这四种酶的mRNA，中性粒细胞微粒体以硫柳汞敏感的方式将花生四烯酰基链结合到磷脂酰肌醇、磷脂酰胆碱、PS和磷脂酰乙醇胺中。这些结果强烈暗示MBOAT5和MBOAT7参与花生四烯酸循环，从而调节中性粒细胞游离花生四烯酸水平和白三烯合成。
The cycle of deacylation and reacylation of phospholipids plays a critical role in regulating availability of arachidonic acid for eicosanoid production. The major yeast lysophospholipid acyltransferase, Ale1p, is related to mammalian membrane-bound O-acyltransferase (MBOAT) proteins. We expressed four human MBOATs in yeast strains lacking Ale1p and studied their acyl-CoA and lysophospholipid specificities using novel mass spectrometry-based enzyme assays. MBOAT1 is a lysophosphatidylserine (lyso-PS) acyltransferase with preference for oleoyl-CoA. MBOAT2 also prefers oleoyl-CoA, using lysophosphatidic acid and lysophosphatidylethanolamine as acyl acceptors. MBOAT5 prefers lysophosphatidylcholine and lyso-PS to incorporate linoleoyl and arachidonoyl chains. MBOAT7 is a lysophosphatidylinositol acyltransferase with remarkable specificity for arachidonoyl-CoA. MBOAT5 and MBOAT7 are particularly susceptible to inhibition by thimerosal. Human neutrophils express mRNA for these four enzymes, and neutrophil microsomes incorporate arachidonoyl chains into phosphatidylinositol, phosphatidylcholine, PS, and phosphatidylethanolamine in a thimerosal-sensitive manner. These results strongly implicate MBOAT5 and MBOAT7 in arachidonate recycling, thus regulating free arachidonic acid levels and leukotriene synthesis in neutrophils.