Biosynthesis of Glycerol Ether Phospholipids
المؤلف:
Peter J. Kennelly, Kathleen M. Botham, Owen P. McGuinness, Victor W. Rodwell, P. Anthony Weil
المصدر:
Harpers Illustrated Biochemistry
الجزء والصفحة:
32nd edition.p242
2025-07-20
392
In glycerol ether phospholipids, one or more of the glycerol carbons is attached to a hydrocarbon chain by an ether linkage rather than an ester bond. Plasmalogens and PAF are important examples of this type of lipid. The biosynthetic pathway is located in peroxisomes. The precursor dihydroxyacetone phosphate combines with acyl-CoA to give 1-acyldihydroxyacetone phosphate, and the ether link is formed in the next reaction, producing 1-alkyldihydroxyacetone phosphate, which is then converted to 1-alkylglycerol 3-phosphate (Figure 1). After further acylation in the 2 position, the resulting 1-alkyl 2-acylglycerol 3-phosphate (analogous to phosphatidate in Figure 2) is hydrolyzed to give 1-alkyl-2-acylglycerol. As in the pathway for phospholipid biosynthesis (see Figure 2), the next steps in the formation of plasmalogens and PAF require CDP-ethanolamine and CDP-choline, respectively. Plasmalogens, which comprise much of the phospholipid in mitochondria, are produced by desaturation of the resulting 3-phosphoethanolamine derivative (see Figure 1), while PAF (1-alkyl-2-acetyl-sn-glycerol-3-phosphocholine) is synthesized by acetylation of the corresponding 3-phosphocholine derivative. Production of PAF occurs in many cell types, but particularly leukocytes and endothelial cells. It was recognized initially for its platelet aggregating properties, but is now known to mediate inflammation, and can contribute to allergic reactions and shock.
Fig1. Biosynthesis of ether lipids, including plasmalogens, and platelet-activating factor (PAF). In the de novo pathway for PAF synthesis, acetyl-CoA is incorporated at stage*, avoiding the last two steps in the pathway shown here.
Fig2. Biosynthesis of triacylglycerol and phospholipids. 1, monoacylglycerol pathway; 2, glycerol phosphate pathway. Phosphatidylethanolamine may be formed from ethanolamine by a pathway similar to that shown for the formation of phosphatidylcholine from choline.
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