Fatty acid composition of brain glycerophospholipids in peroxisomal disorders.

This paper shows for the first time the differential fatty acid composition of ethanolamine plasmalogens (EP) and phosphatidylethanolamine (PE) in the brains of 12 patients with disorders of peroxisomal biogenesis and compares the results to normal values for the age. Other important glycerophospholipids (GPL), such as phosphatidylserine (PS) and phosphatidylcholine (PC), are also included in this study. GPL were separated by two-dimensional thin-layer chromatography, and their fatty acid composition was determined by capillary column gas-liquid chromatography. Total brain GPL were slightly decreased in peroxisomal disorders (27.98+/-2.95 micromol/g in the patients against 34.5+/-6.21 micromol/g in age-matched controls, P = 0.005), and the distribution of the different GPL classes was much altered. In confirmation of known data, EP were very much decreased (2.18+/-1.3 micromol/g in the patients against 6.9+/-2.3 micromol/g in controls) at the expense of PE, which was increased (8.58+/-2.17 micromol/g in the patients against 5.97+/-0.58 micromol/g in controls, P<0.005). PS and PC were both significantly decreased (P = 0.0001 and P = 0.037, respectively). The polyunsaturated fatty acid (PUFA) composition of all the GPL fractions was markedly abnormal. In absolute terms, docosahexaenoic acid (22:6n-3) was drastically decreased in all GPL classes (always at the P<0.0001 level) while arachidonic acid (20:4n-6) was increased in PE and PS (P<0.001 in both cases). In the alkenyl acyl form, EP, 22:6n-3, and 20:4n-6 were both very significantly decreased (P<0.0001), although the former was always the most affected. The myelin PUFA adrenic acid (22:4n-6) was decreased in EP (P<0.0001) and slightly increased in PS (P<0.05). The changes found confirm that 22:6n-3 deficiency is a predominant defect in the brain in peroxisomal disorders.