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Phospholipase A2 catalysis and lipid mediator lipidomics.


ABSTRACT: Phospholipase A2 (PLA2) enzymes are the upstream regulators of the eicosanoid pathway liberating free arachidonic acid from the sn-2 position of membrane phospholipids. Free intracellular arachidonic acid serves as a substrate for the eicosanoid biosynthetic enzymes including cyclooxygenases, lipoxygenases, and cytochrome P450s that lead to inflammation. The Group IVA cytosolic (cPLA2), Group VIA calcium-independent (iPLA2), and Group V secreted (sPLA2) are three well-characterized human enzymes that have been implicated in eicosanoid formation. In this review, we will introduce and summarize the regulation of catalytic activity and cellular localization, structural characteristics, interfacial activation and kinetics, substrate specificity, inhibitor binding and interactions, and the downstream implications for eicosanoid biosynthesis of these three important PLA2 enzymes.

SUBMITTER: Mouchlis VD 

PROVIDER: S-EPMC6483111 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Phospholipase A<sub>2</sub> catalysis and lipid mediator lipidomics.

Mouchlis Varnavas D VD   Dennis Edward A EA  

Biochimica et biophysica acta. Molecular and cell biology of lipids 20180823 6


Phospholipase A<sub>2</sub> (PLA<sub>2</sub>) enzymes are the upstream regulators of the eicosanoid pathway liberating free arachidonic acid from the sn-2 position of membrane phospholipids. Free intracellular arachidonic acid serves as a substrate for the eicosanoid biosynthetic enzymes including cyclooxygenases, lipoxygenases, and cytochrome P450s that lead to inflammation. The Group IVA cytosolic (cPLA<sub>2</sub>), Group VIA calcium-independent (iPLA<sub>2</sub>), and Group V secreted (sPLA<  ...[more]

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