Pulmonary surfactant is a complex of phospholipids

This article is available online at http://www.jlr.org Pulmonary surfactant is a complex of phospholipids ( 90%) and proteins ( 10%) that reduces the surface tension in the alveoli of the lung ( 1, 2 ). Pulmonary surfactant is crucial for normal breathing and its defi ciency leads to fatal respiratory distress syndromes ( 3 ). The major phospholipids in pulmonary surfactant are phosphatidylcholine (PC) and phosphatidylglycerol (PG). Among the species of PC and PG, dipalmitoyl-PC (DPPC) and disaturated-PG (DSPG) are the most abundant ( 1 ). Although the lipid composition of pulmonary surfactant has been well characterized, the enzyme(s) involved in their biosynthesis remained unclear. The acyl-chain composition of phospholipids is mainly determined by a deacylation-reacylation cycle named Lands’ cycle ( 4 ). The last step of Lands’ cycle is mediated by lysophospholipid acyltransferases, including lysophosphatidylcholine acyltransferases (LPCATs) ( 5, 6 ). We and others have previously reported the cloning of four murine LPCATs, designated LPCAT1-4 1 ( 5–10 ). Among them, murine LPCAT1 (mLPCAT1, AB244717) exhibits LPCAT, lysophosphatidylglycerol acyltransferase (LPGAT), and lyso-platelet-activating factor acetyltransferase (lyso-PAF AT) activities ( 7, 11 ). mLPCAT1 prefers saturated acylCoAs as substrates, in accordance with the acyl-chain composition of pulmonary surfactant lipids, and is highly expressed in the lung, where pulmonary surfactant is genAbstract 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.