Phospholipid incorporation and metabolic conversion of n-3 polyunsaturated fatty acids in the Y79 retinoblastoma cell line

The metabolic conversion of n‐3 fatty acids was studied in the human Y79 retinoblastoma cell line. Cultured cells were exposed to increasing concentrations of either 18:3n‐3, 22:5n‐3, or 22:6n‐3, and their phospholipid fatty acid composition was analyzed after 72 hr. Cells internalized the supplemental fatty acids and proceeded to their metabolic conversion. Supplemental 22:6n‐3 was directly esterified into cell phospholipids, at levels typical for normal neural retinas (41% by weight of phosphatidylethanolamine fatty acids, and 24% of phosphatidylcholine fatty acids). In contrast, 18:3n‐3 was mainly converted to 20:5n‐3 and 22:5n‐3, both of which appeared in cell phospholipids after exposure to low external concentrations of 18:3n‐3 (10 μg/ml). Y79 cells can proceed to the metabolic conversion of 18:3n‐3 through elongation and Δ6‐ and Δ5‐desaturation. When cells were exposed to high external concentrations of 18:3n‐3 (30 μg/ml), the supplemental fatty acid was directly incorporated, and its relative content increased in both phospholipid classes to the detriment of all other n‐3 fatty acids. Cells cultured in the presence of 22:5n‐3 did not incorporate 22:6n‐3 into their phospholipids but did incorporate 20:5n‐3 and 22:5n‐3. The data suggest that Y79 cells can proceed to the microsomal steps of n‐3 metabolism, involving elongation, desaturation, and chain shortening of 22C fatty acids. Although Y79 cells avidly used supplemental 22:6n‐3 for phospholipid incorporation at levels typical for normal photoreceptor cells, they failed to match such levels through metabolic conversion of n‐3 parent fatty acids. The terminal step of the very long‐chain polyunsaturated fatty acid synthesis, consisting in Δ6‐desaturation followed by peroxisomal chain shortening of 24C‐fatty acids, could be rate‐limiting in Y79 cells. J. Neurosci. Res. 60:678–685, 2000 © 2000 Wiley‐Liss, Inc.