Biosynthesis of phosphatidylcholine by human lysophosphatidylcholine acyltransferase 1
Biosynthesis of phosphatidylcholine by human lysophosphatidylcholine acyltransferase 1
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DOI：
10.1194/jlr.m800500-jlr200
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发表时间：
2009-09-01
影响因子：
6.5
通讯作者：
Shimizu, Takao
中科院分区：
文献类型：
--
作者：
Harayama, Takeshi;Shindou, Hideo;Shimizu, Takao
肺表面活性剂是一种磷脂和蛋白质的复合体，分布在肺肺泡壁。它能降低肺泡的表面张力，对正常呼吸至关重要。肺表面活性剂磷脂主要由磷脂酰胆碱（PC）和磷脂酰甘油（PG）组成。虽然肺表面活性剂的磷脂组成是众所周知的，但参与其生物合成的酶仍然不清楚。我们之前报道了小鼠溶血磷脂酰转移酶1 （mLPCAT1）作为肺表面活性剂磷脂的潜在生物合成酶的克隆。mLPCAT1具有溶血磷脂酰胆碱酰基转移酶（LPCAT）和溶血磷脂酰甘油酰基转移酶（LPCAT）活性，分别生成PC和PG。然而，人类LPCAT1 （hLPCAT1）的酶活性仍然存在争议。我们在这里报道了hLPCAT1具有LPCAT和LPCAT活性。n -乙基马来酰亚胺抑制了hLPCAT1的活性，表明某些半胱氨酸残基对催化的重要性。我们在hLPCAT1中发现了一个保守的半胱氨酸（Cys(211)），这对其活性至关重要。对LPCAT1近亲同系物的进化分析表明，它出现在硬骨鱼进化之前，并表明LPCAT1可能随着肺的进化而进化，以促进呼吸。hLPCAT1 mRNA在人肺中高表达。我们认为hLPCAT1是肺表面活性剂磷脂的生物合成酶。Harayama， T.， H. Shindou和T. Shimizu。人溶血磷脂酰转移酶合成磷脂酰胆碱的研究[j] .油脂杂志。2009。: 1824 - 1831。
Pulmonary surfactant is a complex of phospholipids and proteins lining the alveolar walls of the lung. It reduces surface tension in the alveoli, and is critical for normal respiration. Pulmonary surfactant phospholipids consist mainly of phosphatidylcholine (PC) and phosphatidylglycerol (PG). Although the phospholipid composition of pulmonary surfactant is well known, the enzyme(s) involved in its biosynthesis have remained obscure. We previously reported the cloning of murine lysophosphatidylcholine acyltransferase 1 (mLPCAT1) as a potential biosynthetic enzyme of pulmonary surfactant phospholipids. mLPCAT1 exhibits lysophosphatidylcholine acyltransferase (LPCAT) and lysophosphatidylglycerol acyltransferase (LPGAT) activities, generating PC and PG, respectively. However, the enzymatic activity of human LPCAT1 (hLPCAT1) remains controversial. We report here that hLPCAT1 possesses LPCAT and LPGAT activities. The activity of hLPCAT1 was inhibited by N-ethylmaleimide, indicating the importance of some cysteine residue(s) for the catalysis. We found a conserved cysteine (Cys(211)) in hLPCAT1 that is crucial for its activity. Evolutionary analyses of the close homologs of LPCAT1 suggest that it appeared before the evolution of teleosts and indicate that LPCAT1 may have evolved along with the lung to facilitate respiration. hLPCAT1 mRNA is highly expressed in the human lung. We propose that hLPCAT1 is the biosynthetic enzyme of pulmonary surfactant phospholipids. Harayama, T., H. Shindou, and T. Shimizu. Biosynthesis of phosphatidylcholine by human lysophosphatidylcholine acyltransferase 1. J. Lipid Res. 2009. 50: 1824-1831.