EFA Specificity in Phospholipid Metabolism
Docosahexaenoic acid (22:6n-3) is the major polyunsaturated fatty acid (PUFA) in the CNS and it accumulates particularly in phosphatidylserine (PS). Brain microsomes from offspring of rats artificially reared on an n-3-deficient diet had much lower 22:6n-3 content (1.7 +/- 0.1%) compared with control animals (15.0 +/- 0.2%). The decrease was accompanied by an increase in docosapentaenoic acid (22:5n-6) content, which replaced the 22:6n-3 phospholipids with 22:5n-6 molecular species, as demonstrated using HPLC/electrospray mass spectrometry. The total polyunsaturated phospholipids in brain microsomes was unchanged however, as a decrease in total PS accompanied increased 1-stearoyl-2-docosapentanoyl (18:0/22:5n-6) species of phosphatidylcholine. Garcia MC, Ward G, Ma YC, Salem N Jr, Kim HY. Effect of docosahexaenoic acid on the synthesis of phosphatidylserine in rat brain in microsomes and C6 glioma cells. J Neurochem 1998 Jan;70(1):24-30.
Reversed phase HPLC-electrospray ionization mass spectrometry showed that depleting n-3 fatty acids from the diet gave 70-80% reduction of 22:6n-3 molecular species in phosphatidylcholine (PC), phosphatidylethanolamine (PE), PE-plasmalogens (PLE), and phosphatidylserine (PS). In general, 22:6n-3 was replaced with 22:5n-6 but the replacement at the molecular species level did not always occur in a reciprocal manner, especially in PC and PLE. While the total PL content was not affected by n-3 deficiency, the relative distribution of PS decreased by 28% with a concomitant increase in PC. Murthy M, Hamilton J, Greiner RS, Moriguchi T, Salem N Jr, Kim HY. Differential effects of n-3 fatty acid deficiency on phospholipid molecular species composition in the rat hippocampus. J Lipid Res 2002 Apr;43(4):611-7
Phospholipid molecular species analysis revealed that in brain cortex, mitochondria, and olfactory bulb 18:0,22:6n-3 was the most abundant species representing 45-65% of total PS. In nonneuronal tissues such as liver and adrenal, 18:0,20:4n-6 was the major PS species. Dietary depletion of n-3 fatty acids during prenatal and postnatal developmental periods decreased the brain 22:6n-3 content by more than 80%, with an approximately 30-35% reduction in total PS in rat brain cortex, brain mitochondria, and olfactory bulb. PS levels in liver and adrenal were unchanged. The observed reduction of PS content in neuronal membranes appears to be due to a dramatic reduction of 18:0,22:6n-3-PS without complete replacement by 18:0,22:5n-6-PS. Hamilton L, Greiner R, Salem N Jr, Kim HY. n-3 fatty acid deficiency decreases phosphatidylserine accumulation selectively in neuronal tissues. Lipids 2000 Aug;35(8):863-9
Long chain polyunsaturates of the n 6 family such as arachidonate (20:4n-6) and docosapentaenoate (22:5n-6) cannot adequately substitute for 22:6n-3. The critical role of highly unsaturated n 3 polyunsaturates in the brain and retina may only be understood within a conceptual framework in which the distinct membrane roles of individual phospholipid species are described as a function of the positions and numbers of double bonds. SALEM N; NIEBYLSKI CD. THE NERVOUS SYSTEM HAS AN ABSOLUTE MOLECULAR SPECIES REQUIREMENT FOR PROPER FUNCTION. MOLECULAR MEMBRANE BIOLOGY 1995; 12: 131 134.
Brain microsomes from offspring of rats artificially reared on an n 3 deficient diet showed a dramatic reduction of 22:6n 3 content (1.7 +/ 0.1%) when compared with control animals (15.0 +/ 0.2%). The decrease was accompanied by an increase in docosapentaenoic acid (22:5n 6) content, which replaced the 22:6n 3 phospholipids with 22:5n 6 molecular species, as demonstrated using HPLC/electrospray mass spectrometry. The n 3 deficiency did not affect the total amount of polyunsaturated phospholipids in brain microsomes; however, it was associated with a decrease in the total polyunsaturated PS content and with increased levels of 1 stearoyl 2 docosapentanoyl (18:0/22:5n 6) species, particularly in phosphatidylcholine. incorporation of [H 3]serine into PS in rat brain microsomes from n 3 deficient animals was slightly but significantly less than that of the control animals. Neuronal and glial PS synthesis is sensitive to changes in the docosahexaenoate levels of phospholipids, and 22:6n 3 may modulate PS synthesis. Garcia MC; Ward G; Ma YC; Salem N; Kim HY. Effect of docosahexaenoic acid on the synthesis of phosphatidylserine in rat brain microsomes and C6 glioma cells. J Neurochem 1998; 70: 24 30.
Updated Sept 2014