Plasmalogen
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Plasmalogens are commonly found in cell membranes in the
Functions
Plasmalogens are found in numerous human tissues, with particular enrichment in the nervous, immune, and cardiovascular systems.[8][9][10] In human heart tissue, nearly 30–40% of choline glycerophospholipids are plasmalogens. Even more striking is the fact that 32% of the glycerophospholipids in the adult human heart and 20% in brain and up to 70% of myelin sheath ethanolamine glycerophospholipids are plasmalogens.[11]
Although the functions of plasmalogens have not yet been fully elucidated, it has been demonstrated that they can protect mammalian cells against the damaging effects of reactive oxygen species.[8][9][10] In addition, they have been implicated as being signaling molecules and modulators of membrane dynamics.
History
Plasmalogens were first described by Feulgen and Voit in 1924 based on studies of tissue sections.
Biosynthesis
Biosynthesis of plasmalogens begins with association of peroxisomal matrix enzymes GNPAT (glycerone phosphate acyl transferase) and AGPS (alkyl-glycerone phosphate synthase) on the luminal side of the peroxisomal membrane.[12] These two enzymes can interact with each other to increase efficiency. Therefore, fibroblasts without AGPS activity have a reduced GNPAT level and activity.[13][14]
The first step of the biosynthesis is catalyzed by GNPAT. This enzyme acylates dihydroxyacetone phosphate at the sn-1 position. This is followed by the exchange of the acyl group for an alkyl group by AGPS.[15] The 1-alkyl-DHAPdihydroxyacetone phosphate is then reduced to 1-O-alkyl-2-hydroxy-sn-glycerophosphate (GPA) by an acyl/alkyl-dihydroxyacetone phosphate
Using CDP-ethanolamine a phosphotransferase forms 1-O-alkyl-2-acyl-sn-GPEtn. After dehydrogenation at the 1- and 2-positions of the alkyl group by an electron transport system and plasmanylethanolamine desaturase the vinyl ether bond of plasmalogens is finally formed. The protein corresponding to plasmanylethanolamine desaturase has been identified and is called CarF in bacteria and PEDS1 (TMEM189) in humans (and animals).[17][18] Plasmenylcholine is formed from 1-O-alkyl-2-acyl-sn-glycerol by choline phosphotransferase. As there is no plasmenylcholine desaturase choline plasmalogens can be formed only after hydrolysis of ethanolamine plasmalogens to 1-O-(1Z-alkenyl)-2-acyl-sn-glycerol that can be modified by choline phosphotransferase and CDP choline.[19][20]
Pathology
Deficits in plasmalogen levels contribute to pathology in Zellweger syndrome.[20]
Plasmalogen-knockout mice show similar alterations like arrest of
Plasmalogen alkyl chains have been shown to promote or inhibit the cell death from ferroptosis, depending on their degree of saturation.[24][25]
During inflammation
During inflammation, neutrophil-derived
Possible disease links
The lack of good methods to assay plasmalogen has created difficulties for scientists to assess how plasmalogen might be involved in human diseases other than RCDP and Zellweger spectrum, in which the involvement is certain.
Evolution
In addition to mammals, plasmalogens are also found in
Recently, it has been demonstrated that the red blood cells of
See also
References
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External links
- Plasmalogens at the U.S. National Library of Medicine Medical Subject Headings (MeSH)