Essential fatty acids and serine as plasmalogen precursors in relation to competing metabolic pathways

Interest in altered ether-lipid metabolism, associated with peroxisomal disorders including adrenoleukodystrophy and Zellweger's syndrome, has highlighted present limitations in our understanding of the biosynthesis and turnover of plasmalogens. These 1-alkenyl ethanolamine phosphoglycerides are major phospholipids in brain, vascular tissue, neutrophils, and most tumors, and they constitute 15-20% of total phospholipids in cultured glioma cell. In glioma, turnover of polyunsaturated acyl chains in the sn-2 position of plasmalogens was examined in relation to selectivity for the (n - 3) and (n - 6) families. Remodeling of acyl chains was more dependent on chain length than on selectivity between families, consistent with plasmalogens enriched in polyunsaturated, but not specifically (n - 3), fatty acids. Extracellular serine was a precursor of serine and ethanolamine phosphoglycerides and was associated with plasmalogens due to decarboxylation and headgroup exchange. Incorporation of extracellular serine ceased within 8 h, even though more than 50% of the label remain in the medium. Analyses of medium and cellular water-soluble components indicated rapid conversion of serine to glycine and other metabolites not used in phospholipid biosynthesis. Thus, nutrient molecules as precursors of plasmalogens are involved in complex competitive interactions. As functions of plasmalogens are clarified, regulation of plasmalogen turnover becomes an increasingly important issue and elucidation of these processes is essential.