Phospholipases (PLs) are a ubiquitous group of enzymes that share the property of hydrolyzing a common substrate, phospholipid.The phospholipases are diverse in the site of action on the phospholipid molecule, their function and mode of action, and their regulation. The diversity of function suggests that phospholipases are critical to life since the continual remodeling of cellular membranes requires the action of one or more phospholipase.

There are four major classes, termed A, B, C and D, which are distinguished by the type of reaction which they catalyze:

  • Phospholipase A
    • Phospholipase A1 – cleaves the SN-1 acyl chain (where SN refers to stereospecific numbering).
    • Phospholipase A2 – cleaves the SN-2 acyl chain, releasing arachidonic acid.
  • Phospholipase B – cleaves both SN-1 and SN-2 acyl chains; this enzyme is also known as a lysophospholipase.
  • Phospholipase C – cleaves before the phosphate, releasing diacylglycerol and a phosphate-containing head group. Phospholipase Cs play a central role in signal transduction, releasing the second messenger inositol triphosphate.
  • Phospholipase D – cleaves after the phosphate, releasing phosphatidic acid and an alcohol.

Types C and D are considered phosphodiesterases.

PLA2s are the most widely studied phospholipases. This particular phospholipase specifically recognizes the sn-2 acyl bond of phospholipids and catalytically hydrolyzes the bond, releasing arachidonic acid and lysophosphatidic acid. Upon downstream modification by cyclooxygenases or lipoxygenases, arachidonic acid is modified into active compounds called eicosanoids. Eicosanoids include prostaglandins and leukotrienes, which are categorized as anti-inflammatory and inflammatory mediators.Two most notable families are secreted and cytosolic phospholipases A2. Other families include Ca2+ independent PLA2 (iPLA2) and lipoprotein-associated PLA2s (lp-PLA2), also known as platelet activating factor acetylhydrolase (PAF-AH).

 Excess levels of sPLA2 is thought to contribute to several inflammatory diseases, and has been shown to promote vascular inflammation correlating with coronary events in coronary artery disease and acute coronary syndrome,and possibly leading to acute respiratory distress syndromeand progression of tonsillitis.In children, excess levels of sPLA2 have been associated with inflammation thought to exacerbate asthma and ocular surface inflammation (dry eye).Increased sPLA2 activity is observed in the cerebrospinal fluid of humans with Alzheimer's disease and multiple sclerosis, and may serve as a marker of increases in permeability of the blood-cerebrospinal fluid barrier.

Increased levels of lp-PLA2 are associated with cardiac disease, and may contribute to atherosclerosis.

PI-PLCs in eukaryotes play a key role in signal transduction cascades generating membrane-associated second messengers (e.g., inositol-1,4,5-triphosphate) in response to cell surface receptor activation.

The PLD family includes enzymes that are involved in phospholipid metabolism, nucleases, toxins, and virus envelope proteins of unknown function.The role of PLD as a virulence factor for Corynebacteriumpseudotuberculosis, Corynebacteriumulcerans, and Arcanobacteriumhaemolyticum has been reported.

In summary, the phospholipases generate numerous lipid products which control much of cellular signaling. Although the importance of these enzymes in eicosanoid metabolism signal translation is not questioned, much remains to be studied regarding the regulation of these enzymes and their pathophysiological roles.