Phospholipase

A phospholipase is an enzyme that converts phospholipids into fatty acids and other lipophilic substances. There are four major classes, termed A, B, C and D.

Phospholipase A (PLA)

Phospholipase A2

Phospholipase A2

Phospholipases A2 (PLA2s) (PDB: 1CJY​, EC 3.1.1.4) are a large family of enzymes that specifically deacylate fatty acids from the 2nd carbon atom (sn2, thus PLA2) of the triglyceride backbone of phospholipids, producing a free fatty acid and a lyso-phospholipid. A large range of fatty acids can be bound to the sn2 position of phospohlipids, including arachidonic acid and eicosapentaenoic acid.

Arachidonic acid is both a signalling molecule and the precursor for other signalling molecules termed eicosanoids. These includeleukotrienes and prostaglandins. Some eicosanoids are synthesized from diacylglycerol, released from the lipid bilayer by phospholipase C (see below).

Phospholipases A2 are ubiquitous enzymes, though the individual enzymes expression patterns differ dramatically. Initially, phospholipases A2 were named based on location of activity (e.g. pancreatic and secretory) or mode of activity (calcium dependent and calcium independent). A much more structured and accurate system has been developed based on genetic homology. For reference see (Six DA, Dennis EA. The expanding superfamily of phospholipase A(2) enzymes: classification and characterization. Biochimica et Biophysica Acta. 2000;1488(1-2):1-19).

Phospholipase B (PLB)

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Phospholipase B is said to be a mixture of both PLA1 and PLA2.It generally acts on lysolecithin(which is formed by the action of PLA2 on lecithin). The action of Phospholipase B rresults in the cleaving of both the fatty acid residues.

Phospholipase C (PLC)

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Phospholipase C (PDB: 1AH7​, EC 3.1.4.3) is a key enzyme in phosphatidylinositol (PIP₂) metabolism. It is activated by either G_{αq protein} (making it part of a G protein-coupled receptor signal transduction pathway) or by transmembrane receptors with intrinsic or associated tyrosine kinase activity.

It converts phosphatidylinositol to inositol triphosphate (IP₃) and diacylglycerol (DAG). These can act on other proteins in cells to increase activity of enzymes, e.g. protein kinase C, or on membrane channels such as calcium in the sarcoplasmic reticulum in smooth muscle.

The Phospholipase C family consists of PLC-δ, -β, -γ and -ε. The molecular weights of each being 85kDa for the δ form, 120-155kDa for both the β and γ forms, and 230-260kDa for the ε form. They all require calcium for catalytic activity.

PLC-δ is activated by high calcium levels and is thought to be the archetypal PLC. PLC-β is activated by G proteins. PLC-γ is activated by receptor tyrosine kinases. PLC-ε is activated by Ras.

All members of the family contain X and Y catalytic domains, SH2 (phosphotyrosine binding) domains are only found in the γ form, and only the ε form contains the RA (Ras Associating) domain. The -β, -δ and -γ forms all contain PH domains.

Phospholipase D (PLD)

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Phospholipase D (EC 3.1.4.50), is located in the plasma membrane and catalyzes the hydrolysis of phosphatidylcholine to form phosphatidic acid (PA) and released choline headgroup. The phosphatidic acid may itself act as a signal molecule (e.g., by activating a PA-activated kinase), or can be hydrolyzed to form diacylglycerol (DAG) by the enzyme PA phosphohydrolase