Platelet-activating factor acetylhydrolase

Definition:

Lipoprotein-associated calcium-independent phospholipase A2 involved in phospholipid catabolism during inflammatory and oxidative stress response. At the lipid-aqueous interface, hydrolyzes the ester bond of fatty acyl group attached at sn-2 position of phospholipids (phospholipase A2 activity). Specifically targets phospholipids with a short-chain fatty acyl group at sn-2 position. Can hydrolyze phospholipids with long fatty acyl chains, only if they carry oxidized functional groups. Hydrolyzes and inactivates platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine), a potent pro-inflammatory signaling lipid that acts through PTAFR on various innate immune cells. Hydrolyzes oxidatively truncated phospholipids carrying an aldehyde group at omega position, preventing their accumulation in low-density lipoprotein (LDL) particles and uncontrolled pro-inflammatory effects. As part of high-density lipoprotein (HDL) particles, can hydrolyze phospholipids having long-chain fatty acyl hydroperoxides at sn-2 position and protect against potential accumulation of these oxylipins in the vascular wall. Catalyzes the release from membrane phospholipids of F2-isoprostanes, lipid biomarkers of cellular oxidative damage.

References:

[1]. L W Tjoelker, et al. Anti-inflammatory properties of a platelet-activating factor acetylhydrolase. Nature. 1995 Apr 6;374(6522):549-53. [Content Brief]

[2]. J H Min, et al. Membrane-bound plasma platelet activating factor acetylhydrolase acts on substrate in the aqueous phase. Biochemistry. 1999 Sep 28;38(39):12935-42. [Content Brief]

[3]. L W Tjoelker, et al. Plasma platelet-activating factor acetylhydrolase is a secreted phospholipase A2 with a catalytic triad. J Biol Chem. 1995 Oct 27;270(43):25481-7. [Content Brief]

[4]. A D Tselepis, et al. N-linked glycosylation of macrophage-derived PAF-AH is a major determinant of enzyme association with plasma HDL. J Lipid Res. 2001 Oct;42(10):1645-54. [Content Brief]

[5]. K E Stremler, et al. Human plasma platelet-activating factor acetylhydrolase. Oxidatively fragmented phospholipids as substrates. J Biol Chem. 1991 Jun 15;266(17):11095-103. [Content Brief]

[6]. D M Stafforini, et al. Molecular basis of the interaction between plasma platelet-activating factor acetylhydrolase and low density lipoprotein. J Biol Chem. 1999 Mar 12;274(11):7018-24. [Content Brief]

[7]. Alison A Gardner, et al. Identification of a domain that mediates association of platelet-activating factor acetylhydrolase with high density lipoprotein. J Biol Chem. 2008 Jun 20;283(25):17099-106. [Content Brief]

[8]. D M Stafforini, et al. Platelet-activating factor acetylhydrolase deficiency. A missense mutation near the active site of an anti-inflammatory phospholipase. J Clin Invest. 1996 Jun 15;97(12):2784-91. [Content Brief]

[9]. Tamas Kriska, et al. Phospholipase action of platelet-activating factor acetylhydrolase, but not paraoxonase-1, on long fatty acyl chain phospholipid hydroperoxides. J Biol Chem. 2007 Jan 5;282(1):100-8. [Content Brief]

[10]. Diana M Stafforini, et al. Release of free F2-isoprostanes from esterified phospholipids is catalyzed by intracellular and plasma platelet-activating factor acetylhydrolases. J Biol Chem. 2006 Feb 24;281(8):4616-23. [Content Brief]

[11]. D G Tew, et al. Purification, properties, sequencing, and cloning of a lipoprotein-associated, serine-dependent phospholipase involved in the oxidative modification of low-density lipoproteins. Arterioscler Thromb Vasc Biol. 1996 Apr;16(4):591-9. [Content Brief]

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