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.
Highlights
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
Both the repair of peroxidized cell membrane phospholipids and a pathway for DPPC synthesis require the combined activity of PLA2 followed by a LPC acyl transferase (LPCAT) activity in order to either regenerate a reduced membrane phospholipid or to remodel phosphatidylcholine (PC) to produce DPPC
We have previously established that Prdx6 is a bifunctional enzyme with phospholipid hydroperoxide peroxidase and PLA2 activities
Summary
The phospholipase A2 (PLA2) activity of peroxiredoxin (Prdx) 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. The PLA2 activity participates in the turnover of lung surfactant phospholipids with a major function in phospholipid remodeling to generate the dipalmitoylphosphatidylcholine (DPPC) that is the surface-active lipid component of the lung surfactant [11,12,13,14,15] Both the repair of peroxidized cell membrane phospholipids and a pathway for DPPC synthesis require the combined activity of PLA2 followed by a LPC acyl transferase (LPCAT) activity in order to either regenerate a reduced membrane phospholipid or to remodel phosphatidylcholine (PC) to produce DPPC.
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