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 microg/ml). Y79 cells can proceed to the metabolic conversion of 18:3n-3 through elongation and Delta6- and Delta5-desaturation. When cells were exposed to high external concentrations of 18:3n-3 (30 microg/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 Delta6-desaturation followed by peroxisomal chain shortening of 24C-fatty acids, could be rate-limiting in Y79 cells.
Goustard-Langelier
B
B
Institut National de la Recherche Agronomique, Laboratoire de Nutrition et Sécurité Alimentaire, Jouy-en-Josas, France.
Alessandri
J M
JM
Raguenez
G
G
Durand
G
G
Courtois
Y
Y
D004281:Docosahexaenoic Acids / Q000378:metabolism / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D015525:Fatty Acids, Omega-3 / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D012160:Retina / Q000187:drug effects* / Q000378:metabolism*; D012175:Retinoblastoma; D013997:Time Factors; D014407:Tumor Cells, Cultured; D017962:alpha-Linolenic Acid / Q000378:metabolism
D015525:Fatty Acids, Omega-3; D010743:Phospholipids; D017962:alpha-Linolenic Acid; D004281:Docosahexaenoic Acids