Plasmalogen
Plasmalogens are ether lipids that resemble structurally the phosphatidylcholines and phosphatidylethanolamines. The difference is that the terminal carbon atom of the glycerol is present in place of an enol ether of a fatty acid ester. The second, as the ester -bound fatty acid is usually polyunsaturated. About 10% of the phospholipids of the brain and the muscles belong to the group of plasmalogens. Since a context of plasmalogens with various neuropathologies seems to be, they are the subject of intensive research.
Functions
Plasmalogens are present in many human tissues, especially in larger quantities in the nervous - immune and cardiovascular system. Tissue-specific distinction can be made that in the human heart increases occur plasmalogens with choline as head group (so-called phosphatidylcholine plasmalogens ), while mainly phosphatidyl ethanolamine can be found as the top group in the myelin sheaths of the nervous system.
Although the functions of plasmalogens are not yet fully understood, it could be shown that they protect mammalian cells against oxidative damage. It is commonly believed that they play a role in signal transduction.
Biosynthesis
The biosynthesis of plasmalogens occurs in the peroxisomes and the endoplasmic reticulum ( ER). At the beginning created a complex of enzymes GNPAT ( glycerol phosphate acyltransferase ) and AGPS (alkyl - glycerol phosphate synthase ) on the luminal side of the peroxisomal membrane. It has been shown that in the absence of, for example, the AGPS the cooperating enzyme GNPAT suffers a loss of activity. The first step of the synthesis is initiated by GNPAT. DHAP is acylated ( dihydroxyacetone ) at the sn -1 position. Then the AGPS exchanges the acyl group with an alkyl group. The resulting 1-alkyl- DHAP is reduced to 1-O -alkyl-2 -hydroxy -sn- glycerophosphate ( GPA). This reaction is catalysed by an acyl / alkyl - DHAP - reductase that is localized on the ER and in the peroxisomal membrane.
All other modifications are now taking place in the ER. First here acyl residue is suspended from the sn -2 position by an alkyl / acyl- GPA acyltransferase, wherein the phosphate group is removed by a phosphatase. This results in 1-O -alkyl-2 -acyl -sn- glycerol. A phosphotransferase now formed with CDP - ethanolamine, 1-O -alkyl-2 -acyl -sn- GPEtn. After dehydration at the 1 - and 2- position of the alkyl group through an electron transport system, and a Plasmenylethanolamin desaturase PL typical vinyl - ether bond is formed finally. Plasmenylcholine formed from 1-O -alkyl-2 -acyl -sn- glycerol with the choline phosphotransferase.
Because there is no plasmenylcholine desaturase, choline - PLs can only arise through a detour. Thereby ethanolamine PLs are hydrolyzed to form 1- O-( 1Z - alkenyl )-2- acyl -sn- glycerol and modified by the enzyme choline phosphotransferase with CDP-choline as so choline PLs arise.
Pathologies
Zellweger syndrome is inter alia characterized by a plasmalogen deficiency since peroxisomes are degraded and contain almost no enzymes. So they can not synthesize plasmalogens.
A reduced content of plasmalogens in the brain have been associated with Alzheimer 's disease, X -linked adrenoleukodystrophy, and Down's syndrome.