Phospholipase C

Cleavage sites of phospholipases. Phospholipase C enzymes cut just before the phosphate attached to the R₃ moiety.

Phospholipase C is a class of enzymes that cleave phospholipids just before the phosphate group (see figure). It is most commonly taken to be synonymous with the human forms of this enzyme, which plays an important role in eukaryotic cell physiology, particularly signal transduction pathways. Thirteen kinds of mammalian phospholipase C are classified into six models (β, γ, δ, ε, ζ, η) according to structure.

Human variant

The human variant has EC 3.1.4.11.

Activation

Receptors that activate this pathway are mainly G-protein coupled receptors coupled to the G_αq subunit, including:

• 5-HT₂ serotonergic receptors^[1]
• α₁ (Alpha-1) adrenergic receptors^[2]
• Calcitonin receptor^[1]
• H₁ histamine receptor^[1]
• Metabotropic glutamate receptor, Group I^[1]
• M₁, M₃, and M₅ muscarinic receptors^[1]

Other, minor, activators than G_αq are:

• MAP kinase. Activators of this pathway include PDGF and FGF.^[2]
• βγ-complex of heterotrimeric G-proteins, as in a minor pathway of growth hormone release by growth hormone releasing hormone.^[3]

Effects

PLC cleaves a phospholipid. In the process, phosphatidylinositol 4,5-bisphosphate (PIP₂) is cleaved into diacyl glycerol (DAG) and inositol 1,4,5-triphosphate (IP₃). DAG remains bound to the membrane, and IP₃ is released as a soluble structure into the cytosol. IP₃ then diffuses through the cytosol to bind to IP₃ receptors, particular calcium channels in the endoplasmic reticulum (ER). This causes the cytosolic concentration of calcium to increase, causing a cascade of intracellular changes and activity.^[4] In addition, calcium and DAG together works to activate protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity.^[4] End effects include taste, tumor promotion, etc.^[4]

In other organisms

Other phospholipase C enzymes have been identified in bacteria and in trypanosomes, each with their own EC number.

• Phosphoinositide phospholipase C EC 3.1.4.11 The main form found in eukaryotes, especially mammals.

• Zinc dependent phospholipase C family of bacterial enzymes EC 3.1.4.3 that includes alpha toxins

• Phosphatidylinositol diacylglycerol-lyase EC 4.6.1.13 Another related bacterial enzyme.

• Glycosylphosphatidylinositol diacylglycerol-lyase EC 4.6.1.14 A trypanosomal enzyme.

References