Answer to Question L-04 about Lipids.
Answer (e): Phosphoglycerides.
General structure of Phosphoglycerides
The two acyl groups appear in the orange area, linked to the glycerol (in the white area) by ester (carboxylic ester) linkages. The hydrocarbon chain of the acyl groups represents the hydrophobic or apolar part of these molecules. In the green area, appears the Phosphate linked through a phosphoric ester linkage to the glycerol, but also to X, the hydroxylated compound whose OH group has formed an ester linkage with the Phosphoric acid (Phosphate, at physiological pH). This is the polar part of the molecule.
Depending on the identity of X, the phosphoglyceride can be:
• Phosphatidate (if X is an Hydrogen)
• Phosphatidyl choline aka lecithin (if X is choline)
• Phosphatidyl ethanolamine (if X is ethanolamine)
• Phosphatidyl serine (if X is serine)
• Phosphatidyl glycerol (if X is another glycerol)
• Phosphatidyl inositol (if X is inositol)
• Cardiolipin (if X is a glycerophosphatidate)
In the group of Phosphoglycerides are also included other compounds that do not have the Phosphatidyl structure, since these compounds have linked to the C1 of glycerol an alkyl side chain bound through an ether linkage, instead of the acyl side chain linked through an ester linkage, characteristic of the phosphatidyl group. These compounds are known as Ether lipids. The most important representatives of this kind of phosphoglycerols are Plamalogens and Platelet Activating Factor.
Platelet activating factor
The functions of phosphoglycerides include:
• Structure of cell membranes
• Reservoir for intracellular messengers
• Anchors of some proteins for cell membranes
• Stabilization of protein structure
• Cofactors of enzymes
• Biological detergents
– Surfactants in lungs
– Solubilization of non polar lipids in lipoproteins.
The individual role of the main phosphoglycerides is described below:
Phosphatidic acid: Metabolic intermediary and precursor in the synthesis of other phospholipids and triacylglycerol. It has been implicated in signaling process, when released from other phospholipids by the action of phospholipase D (Phosphatidic acid and related lipids)
Phosphatidyl glycerol: It is a component of membranes, and the main phospholipid component in certain bacteria. In human tissues it is found mainly in mitochondria. It is also the second most abundant phospholipid in lung surfactant and is a precursor of cardiolipin.
Phosphatidyl ethanolamine (cephaline) is the second most abundant phospholipid in animals. It has a key role in the structure of membranes, with a specific role in stabilizing the structure of some proteins, allowing them a transporting or enzymatic function in or at the membrane. (Phosphatidyl ethanolamine and related lipids.)
Phosphatidyl Choline is the most abundant phospholipid in animals and is the key building block of membranes. It is also the main phospholipid of plasmatic lipoproteins. The role of phosphatidyl choline as lung surfactant and its medical implications have been discussed in other post. Phosphatidyl choline may have a role in the signaling system especially in the nucleus, by generating diacylglcycerol under the action of phospholipases C and/or D. (Phosphatidyl Choline and related lipids)
Phosphatidyl Serine is located mainly in the inner surface of the plasma membrane. It is a required cofactor of protein Kinases C and other enzymes and consequently has an important role in the intracellular signaling system, and participates in coagulation, apoptosis and mineral deposition in bones. (Phosphatidyl serine: structure, occurrence, biochemistry and analysis)
Phosphatidyl inositol and phosphorylated derivatives are important phospholipids with roles in the cellular signaling system, in the synthesis of eicosanoids, as a component of membranes and as membrane anchors for protein. The most important phosphorylated derivatives are phosphoinositol 4 (P) and Phosphoinositol 4, 5 diphosphate.
The key role of phosphatidyl inositol 4,5 diphosphate in the Phospholipase C system, yielding different second messengers, has been described elsewhere in this site. Phosphatidyl inositol is the main source of arachidonate in peripheral tissues. (Arachidonate is the precursor of the eicosanoid lipids prostaglandins, leukotrienes and thromboxanes).
Cardiolipin is a very important phospholipid in mitochondrial membrane. It is particularly abundant in heart tissue, where it was discovered. Most of the cardiolipin in humans have four linoleyl groups in its structure. Cardiolipin appears almost exclusively in the inner membrane of the mitochondria, where it interacts with various proteins. It has been demonstrated that cardiolipin is necessary for the activity of different enzymes, including enzymes of the respiratory chain. Cardiolipin apparently participates also in steroidogenesis, apoptosis, regulation of gene expression and the minor quantities found in plasmatic lipoproteins have anticoagulant functions.
Barth Syndrome, a cardiomyopathie in children, is associated to the deficit of tafazzin, a phospholipid acyltransferase that participates in the remodeling of cardiolipin (e.g. in the introduction of specific fatty acids during the synthesis). Children with this X-linked disease have decreased quantities of tetralinoleyl cardiolipin and apparently, it is translated as a reduction in the efficiency of the respiratory chain in the heart muscle.(Cardiolipin: Structure, occurrence, biology and analysis.pdf)
Plasmalogens: Structure of membranes, where they act as reservoirs of polyunsaturated fatty acids that may act as intracellular signaling compounds.
Platelet Activation Factor: This lipid is not stored in a preformed state, but synthesized when necessary as a response to inflammatory process. It is one of the most potent bioactive molecules known, causing effects at concentrations as low as 10 -12 mol/L. It participates in the signaling process activating cytoplasmatic Phospholipases A and C. Phospholipase C produces a release of Ca++ and activation of Protein Kinase C (see related post). It has proinflammatory properties and has been implicated in the pathogenesis of different diseases, from allergic to thrombotic conditions. (Platelet Activating Factor, Chemistry and Biology.)
For more information about Glycerophospholipids, check:
Complex glycerolipids in http://www.lipidlibrary.co.uk/Lipids/complex.html
Phosphoglycerides in Cyberlipid center: http://www.cyberlipid.org/phlip/pgly02.htm#1