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Plasmalogen Synthesis Pathway
Plasmalogens are a class of glycerophospholipids that contain one vinyl-ester linked long chain alcohol group in place of one ester-linked fatty acid chain found in other glycerophospholipids. As with the common glycerophospholipids, the polar head group of the plasmalogens is composed of ethanolamine, serine, or choline. Plasmalogens are relatively rare in some tissues but form a significant fraction of the membranes in nervous tissue. Some of the steps in plasmalogen biosynthesis are localized in peroxisomes, and some peroxisomal disorders impair plasmalogen biosynthesis. One of the starting materials for plasmalogen biosynthesis is dihydroxyacetone phosphate from glycolysis, which is used to form the glycerol backbone of the plasmalogen. In the first step, the three-carbon backbone is esterified with a fatty acid. This fatty acid ester is then exchanged leaving an ether-linked long-chain alcohol bound. Reduction of the carbonyl on the dihydroxyacetone backbone leaves a hydroxy group to be esterified with another fatty acid side chain. The polar head group such as ethanolamine is then newed, and the alcohol chain modified in the last step to form the vinyl-alcohol side chain that characterizes plasmalogens. Plasmalogens serve as a starting point for the release of arachidonic acid by phospholipase A2 and the synthesis of signaling molecules derived from arachidonic acid such as prostaglandins. One plasmalogen called PAF acts through a G-protein coupled receptor as a potent platelet activator and clotting agent. The double bond of plasmalogens makes them more sensitive to oxidation than other membrane lipids, and may help to protect cells from oxidative damage. A decrease in the abundance of plasmalogens has been observed in some neurological disorders such as Alzheimer's disease. (NCI Thesaurus/BIOCARTA)
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