title: A novel lysophosphatidylcholine acyl transferase activity is expressed by peroxiredoxin 6.
abstract: The phospholipase A2(PLA2) activity of peroxiredoxin (Prdx)6 has important physiological roles in the synthesis of lung surfactant and in the repair of peroxidized cell membranes. These functions require the activity of a lysophospholipid acyl transferase as a critical component of the phospholipid remodeling pathway. We now describe a lysophosphatidylcholine acyl transferase (LPCAT) activity for Prdx6 that showed a strong preference for lysophosphatidylcholine (LPC) as the head group and for palmitoyl CoA in the acylation reaction. The calculated kinetic constants for acylation wereKm18 μM andVmax30 nmol/min/mg protein; theVmaxwas increased 25-fold by phosphorylation of the protein whileKmwas unchanged. Study of recombinant protein in vitro and in mouse pulmonary microvascular endothelial cells infected with a lentiviral vector construct indicated that amino acid D31 is crucial for LPCAT activity. A linear incorporation of labeled fatty acyl CoA into dipalmitoyl phosphatidylcholine (PC) indicated that LPC generated by Prdx6 PLA2activity remained bound to the enzyme for the reacylation reaction. Prdx6 is the first LPCAT enzyme with demonstrated cytoplasmic localization. Thus, Prdx6 is a complete enzyme comprising both PLA2and LPCAT activities for the remodeling pathway of PC synthesis or for repair of membrane lipid peroxidation.
authors.affiliation: Institute for Environmental Medicine and the Department of Physiology University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104 abf@mail.med.upenn.edu.
authors.forename: Aron B
authors.initials: AB
authors.lastname: Fisher
authors.affiliation: Institute for Environmental Medicine and the Department of Physiology University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors.forename: Chandra
authors.initials: C
authors.lastname: Dodia
authors.affiliation: Institute for Environmental Medicine and the Department of Physiology University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors.forename: Elena M
authors.initials: EM
authors.lastname: Sorokina
authors.affiliation: Institute for Environmental Medicine and the Department of Physiology University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute for Environmental Medicine and the Department of Physiology University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors.forename: Suiping
authors.initials: S
authors.lastname: Zhou
authors.affiliation: Penn Gene Targeting Core and Laboratory, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors.forename: Tobias
authors.initials: T
authors.lastname: Raabe
authors.affiliation: Institute for Environmental Medicine and the Department of Physiology University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104.
authors.forename: Sheldon I
authors.initials: SI
authors.lastname: Feinstein
mesh_terms: D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000378:metabolism*; D000215:Acylation; D000595:Amino Acid Sequence; D000818:Animals; D003593:Cytoplasm / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008244:Lysophosphatidylcholines / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D054465:Peroxiredoxin VI / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D013379:Substrate Specificity
chemical_list: D008244:Lysophosphatidylcholines; D054465:Peroxiredoxin VI; D008243:1-Acylglycerophosphocholine O-Acyltransferase
keywords: cell membrane repair; lamellar bodies; lung endothelial cells; phospholipase A2; phospholipids/metabolism; pulmonary surfactant
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