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Journal of Lipid Research, Vol. 50, 1824-1831, September 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Biosynthesis of phosphatidylcholine by human lysophosphatidylcholine acyltransferase 1¹

Takeshi Harayama, Hideo Shindou² and Takao Shimizu

Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 Japan

² To whom correspondence should be addressed. e-mail: hshindou-tky{at}umin.ac.jp

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 (Cys²¹¹) 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.

Supplementary key words lyso-platelet-activating factor acetyltransferase • lysophosphatidylglycerol acyltransferase • pulmonary surfactant • N-ethylmaleimide • evolution • lung

Abbreviations: AGPAT, 1-acylglycerol-3-phosphate-O-acyltransferase; BLAST, Basic Local Alignment Search Tool; CHO, Chinese hamster ovary; DPPC, dipalmitoylphosphatidylcholine; DSPG, disaturated phosphatidylglycerol; GPAT, glycerol-3-phosphate acyltransferase; hLPCAT1, human lysophosphatidylcholine acyltransferase 1; LPAAT, lysophosphatidic acid acyltransferase; LPCAT, lysophosphatidylcholine acyltransferase; LPEAT2, lysophosphatidylethanolamine acyltransferase 2; LPGAT, lysophosphatidylglycerol acyltransferase; lyso-PAF AT, lyso-platelet-activating factor acetyltransferase; mLPCAT1, murine lysophosphatidylcholine acyltransferase 1; NEM, N-ethylmaleimide; PAF, platelet-activating factor; PAFR, platelet-activating factor receptor; PC, phosphatidylcholine; PG, phosphatidylglycerol; rLPCAT1, rat lysophosphatidylcholine acyltransferase 1

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