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J Lipid Res. 2018 Jul;59(7):1132-1147. doi: 10.1194/jlr.R082578. Epub 2018 May 1.

The phospholipase A2 activity of peroxiredoxin 6.

Author information

1
Institute for Environmental Medicine of the Department of Physiology, University of Pennsylvania, Philadelphia, PA 19103 ABF@UPenn.edu.

Abstract

Peroxiredoxin 6 (Prdx6) is a Ca2+-independent intracellular phospholipase A2 (called aiPLA2) that is localized to cytosol, lysosomes, and lysosomal-related organelles. Activity is minimal at cytosolic pH but is increased significantly with enzyme phosphorylation, at acidic pH, and in the presence of oxidized phospholipid substrate; maximal activity with phosphorylated aiPLA2 is ∼2 µmol/min/mg protein. Prdx6 is a "moonlighting" protein that also expresses glutathione peroxidase and lysophosphatidylcholine acyl transferase activities. The catalytic site for aiPLA2 activity is an S32-H26-D140 triad; S32-H26 is also the phospholipid binding site. Activity is inhibited by a serine "protease" inhibitor (diethyl p-nitrophenyl phosphate), an analog of the PLA2 transition state [1-hexadecyl-3-(trifluoroethyl)-sn-glycero-2-phosphomethanol (MJ33)], and by two naturally occurring proteins (surfactant protein A and p67phox), but not by bromoenol lactone. aiPLA2 activity has important physiological roles in the turnover (synthesis and degradation) of lung surfactant phospholipids, in the repair of peroxidized cell membranes, and in the activation of NADPH oxidase type 2 (NOX2). The enzyme has been implicated in acute lung injury, carcinogenesis, neurodegenerative diseases, diabetes, male infertility, and sundry other conditions, although its specific roles have not been well defined. Protein mutations and animal models are now available to further investigate the roles of Prdx6-aiPLA2 activity in normal and pathological physiology.

KEYWORDS:

aiPLA2; antioxidants; lipid peroxidation; lysosomal PLA2; moonlighting protein; phospholipid remodeling; phospholipid turnover; phospholipid/metabolism; phospholipids/phosphatidylcholine; protein phosphorylation

PMID:
29716959
PMCID:
PMC6027911
[Available on 2019-07-01]
DOI:
10.1194/jlr.R082578

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