The Phospholipase A2 Superfamily: Structure, Isozymes, Catalysis, Physiologic and Pathologic Roles

Area of Science:

• Biochemistry
• Enzymology
• Molecular Biology

Background:

• Phospholipase A2 (PLA2) enzymes hydrolyze phospholipids at the sn-2 position, producing free fatty acids and lysophospholipids.
• PLA2s are amphiphilic enzymes that function at water/lipid interfaces, acting on phospholipid assemblies.

Purpose of the Study:

• To review the six major families of PLA2 enzymes: secreted (sPLA2), cytosolic (cPLA2), Ca2+-independent (iPLA2), lipoprotein-associated (LpPLA2), lysosomal (LPLA2), and adipose-tissue-specific (AdPLA2).
• To highlight the structural, mechanistic, substrate specificity, kinetic, and tissue distribution differences among PLA2 families.
• To discuss the physiological and pathological roles of PLA2s, particularly their involvement in diseases.

Main Methods:

• Literature review of the PLA2 superfamily.
• Comparative analysis of PLA2 isoenzyme families based on structure, function, and substrate specificity.
• Discussion of PLA2 involvement in various disease states.

Main Results:

• The PLA2 superfamily consists of at least six distinct isoenzyme families with unique characteristics.
• Significant differences exist in the structure, mechanism of action, substrate specificity, interfacial kinetics, and tissue distribution across PLA2 families.
• PLA2 expression is notably elevated in pathological conditions such as sepsis, inflammation, cancers, glaucoma, obesity, and Alzheimer's disease.

Conclusions:

• PLA2 enzymes are critical in both normal physiology and disease pathogenesis.
• Understanding the diverse roles and characteristics of PLA2 families is essential for therapeutic development.
• Targeting specific PLA2s may offer therapeutic strategies for a range of inflammatory and degenerative diseases.