diacylglycerol

Definition: A diglyceride, or a diacylglycerol (DAG), is a glyceride consisting of two fatty acid chains covalently bonded to a glycerol molecule through ester linkages.

One example is 1-palmitoyl-2-oleoyl-glycerol, which contains side-chains derived from palmitic acid and oleic acid. Diacylglycerols can also have many different combinations of fatty acids attached at both the C-1 and C-2 positions.

Biological functions

 PKC activation in molecular signaling

Diacylglycerol (DAG) functions as a second messenger signaling lipid, and is a product of the hydrolysis of the phospholipid PIP2 (phosphatidyl inositol-bisphosphate) by the enzyme phospholipase C (PLC) (a membrane-bound enzyme) that, through the same reaction, produces inositol triphosphate (IP3).

Although inositol triphosphate (IP3) diffuses into the cytosol, diacylglycerol (DAG) remains within the plasma membrane, due to its hydrophobic properties.

IP3 stimulates the release of calcium ions from the smooth endoplasmic reticulum, whereas DAG is a physiological activator of protein kinase C (PKC).

The production of DAG in the membrane facilitates translocation of PKC from the cytosol to the plasma membrane.

Diacylglycerol can be mimicked by the tumor-promoting compounds phorbol esters.

Other functions

In addition to activating PKC, diacylglycerol has a number of other functions in the cell:

 DAG is a source for prostaglandins.
 DAG is a precursor of the endocannabinoid 2-arachidonoylglycerol.
 DAG is an activator of a subfamily of TRPC (Transient Receptor Potential Canonical) cation channels, TRPC3/6/7.

Metabolism

Synthesis of diacylglycerol begins with glycerol-3-phosphate, which is derived primarily from dihydroxyacetone phosphate, a product of glycolysis (usually in the cytoplasm of liver or adipose tissue cells).

Glycerol-3-phosphate is first acylated with acyl-coenzyme A (acyl-CoA) to form lysophosphatidic acid, which is then acylated with another molecule of acyl-CoA to yield phosphatidic acid. Phosphatidic acid is then de-phosphorylated to form diacylglycerol.

Diacylglycerol is a precursor to triacylglycerol (triglyceride), which is formed in the addition of a third fatty acid to the diacylglycerol under the catalysis of diglyceride acyltransferase.

Since diacylglycerol is synthesized via phosphatidic acid, it will usually contain a saturated fatty acid at the C-1 position on the glycerol moiety and an unsaturated fatty acid at the C-2 position.

See also

 diacylglycerol kinases

• diacylglycerol kinases delta (DGKD)

References

 Griner EM, Kazanietz MG. Protein kinase C and other diacylglycerol effectors in cancer. Nat Rev Cancer. 2007 Apr;7(4):281-94. PMID: 17384583