Function and Inhibition of Intracellular Calcium-independent Phospholipase A2

Jesús Balsinde,Edward A Dennis

doi:10.1074/jbc.272.26.16069

Jesús Balsinde, Edward A Dennis

Open Access

https://doi.org/10.1074/jbc.272.26.16069

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Abstract

Function and Inhibition of Intracellular Calcium-independent Phospholipase A2

Highlights

All of the well studied secretory phospholipase A2s (sPLA2) appear to use a His-Asp catalytic mechanism and require Ca2ϩ to be bound tightly in the active site of the enzyme
While there exists a group of lysosomal independent cytosolic phospholipase A2 (iPLA2) and a group of characterized ectoenzymes with broad specificity, which may be general lipases [8], sequenced and well characterized intracellular iPLA2s are limited to the 80-kDa Group VI iPLA2 and the 29-kDa Group VIII enzyme, which is a platelet-activating factor (PAF) acetyl hydrolase [9]
The importance of the intracellular iPLA2 in control of cell function has not been clearly established at present, despite the fact that iPLA2s have been found to exist in all cells and tissues examined

Summary

Introduction

All of the well studied sPLA2s appear to use a His-Asp catalytic mechanism and require Ca2ϩ to be bound tightly in the active site of the enzyme. One common feature of the two best characterized intracellular iPLA2s, namely the Group VI enzyme present in P388D1 macrophages [12] and CHO cells [14] and a 40-kDa iPLA2 present in myocardial tissue and pancreatic islets [19], is their complete and irreversible inhibition by the mechanism-based inhibitor BEL. BEL has recently been found to inhibit another key enzyme in cellular phospholipid metabolism, the Mg2ϩ-dependent phosphatidic acid phosphohydrolase (PAP-1) [23].

Results

Conclusion