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 cells. 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 remained 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.Key words: plasmalogen, serine, fatty acids, glioma.

Potential diagnostic value of the umbilical artery as a definition of neural fatty acid status of the fetus during its growth: the umbilical artery as a diagnostic tool

Summary Low birth weight (LBW) is associated with handicaps, the most prevelant of which affect the brain or its sensory attributes and have a life long impact. We have therefore been interested in nutrition and fetal growth and have studied the relationship between maternal diet and the outcome of pregnancy. Essential fatty acids are methylene-interrupted, polyenoic fatty acids that are required for cell membrane structure, integrity and function. Some 60% of the structural material of the brain and nervous system is lipid and it uses 20- and 22-carbon-chain-length polyenoic acids specifically in sites of signal transduction and high activity (Fig. 1). We have been interested in the acquisition of these fatty acids during fetal growth and along with deficits of several nutrients found low intakes of essential fatty acids (EFA) in the mothers of LBW babies. In order to test this food intake data we have analysed the lipids of the umbilical artery as representative of fetal tissue. We found surprisingly high proportions of the n − 9 eicosatrienoic acid (20:3, n − 9) and docosatrienoic acid (22:3, n − 9). The 20:3, n − 9 is known as the Mead acid and is recognized as a biochemical index of EFA deficiency [1,2]. The 20:3, n − 9/2:4, n − 6 ratio has been used as a biochemical test of general EFA deficiency and the 22:5, n − 6/ 22:4, n − 6 ratio as a marker of docosahexaenoic or n − 3 deficiency. Both ratios were unusually high. Further analysis of 14 babies of different birth weights produced highly significant Pearson correlation coefficients between birth weights and head circumferences, and these two indices, which were negative, and greater in the ethanolamine phosphoglycerides than in the choline phosphoglycerides of the umbilical artery. The ethanolamine phosphoglycerides are inner membrane lipids and therefore the presence of the Mead acid and high levels of 22:5, n − 6 are statements about the biochemical history of the individual fetus. These indices may therefore have a diagnostic value as a measure of the nutritional status of the fetus during its growth. Because they describe the status of fatty acids specifically used for neural tissue growth, this diagnostic tool has a potential, which needs now to be tested, for assessing risk of neural deficits or damage in, for example, LBW and premature infants.