Lipolytic enzymes are a group of enzymes that break down water-insoluble esters and produce fatty acids. They are used in many industrial processes including detergents, fuels, clothing, beverage and pulp. 

Phospholipase Enzymes

Phospholipase A2 (PLA2):

–Structure/mechanisms of action: PLA2 belongs to the lipolytic family of enzymes that hydrolyze the ester bond at the sn-2 position of the phospholipids. Upon hydrolysis of the phospholipids, PLA2s release free fatty acids and generate lysophospholipids (LPLs). Free fatty acids such as arachidonic acid (AA) and oleic acid (OA) are important sources of energy. (Khan, “The Phospholipase A2 Superfamily: Structure, Isozymes, Catalysis, Physiologic and Pathologic Roles” Intl J. Mol Sci, 24(2), 2023). 

A Ca2+ ion is required for both binding of the substrate and for catalysis. However, Group VI phospholipase A2 enzymes are members of the PLA2 superfamily that are characterized as Ca2+-independent PLA2 (iPLA2) enzymes. (Khan, “The Phospholipase A2 Superfamily: Structure, Isozymes, Catalysis, Physiologic and Pathologic Roles” Intl J. Mol Sci, 24(2), 2023).

PLA2s exist as active enzymes and as inactive PLA2-like proteins in snake venom. PLA2 enzymes catalyse the hydrolysis of the sn-2 ester bond of cell-membrane phospholipids and are classified into 14 groups, from which the groups IA and IIA are present in elapid and viperid venoms. (Fernandes, “The chemistry of snake venom and its medicinal potential” Nature. 6, 451-469 2022). pages451–469 (20pages451–469 (2022)

–Functions:

The PLA2s play important roles both physiologically and pathologically, with their expression increasing significantly in diseases such as sepsis, inflammation, different cancers, glaucoma, obesity and Alzheimer’s disease. Khan, “The Phospholipase A2 Superfamily: Structure, Isozymes, Catalysis, Physiologic and Pathologic Roles” Intl J. Mol Sci, 24(2), 2023).

The PLA2 superfamily has been classified into 16 groups (groups I to XVI), based on the chronology of their discovery, as well as based on their location in the body, substrate specificity. Khan, “The Phospholipase A2 Superfamily: Structure, Isozymes, Catalysis, Physiologic and Pathologic Roles” Intl J. Mol Sci, 24(2), 2023).

PLA2-IIA also plays a major role in host defense via its antimicrobial activity. It degrades bacterial membrane by hydrolyzing phosphatidylethanolamine and phosphatidylglycerol, which are abundant in the bacterial membrane. Blood plasma concentration of sPLA2-IIA can increase up to 500-fold in patients with acute diseases such as sepsis, peritonitis and bacterial infection, compared to healthy persons. (Khan, “The Phospholipase A2 Superfamily: Structure, Isozymes, Catalysis, Physiologic and Pathologic Roles” Intl J. Mol Sci, 24(2), 2023).

Secreted PLA2s, especially groups IIA, V and X, can play an important role in atherosclerosis. A study showed that young adults (age 24 to 39 years) with cardiovascular disease had an increased level of GIIA sPLA2 in their blood plasma, which may contribute to atherogenicity. (Khan, “The Phospholipase A2 Superfamily: Structure, Isozymes, Catalysis, Physiologic and Pathologic Roles” Intl J. Mol Sci, 24(2), 2023).

sPLA2s are widely known to be overexpressed in various tumors and cancer cells. (Khan, “The Phospholipase A2 Superfamily: Structure, Isozymes, Catalysis, Physiologic and Pathologic Roles” Intl J. Mol Sci, 24(2), 2023).