Studies of the modulation of essential fatty acid metabolism by fatty acids in cultured neuroblastoma and glioma cells.
In cultured neuroblastoma cells (N1E-115), the metabolism of the essential fatty acid, linoleic acid (18:2 (n-6)), to arachidonic acid (20:4(n-6)) can be altered by other fatty acids in a manner supporting a concerted action of the modulating fatty acid on the desaturation and chain elongation enzymes. In further examination of mechanisms involved, cultured glioma (C-6) or neuroblastoma-glioma hybrids (NG-108-15) cells showed similar patterns of activation by some fatty acids (e.g., 20:3(n-6) and 20:4(n-6)), and inhibition (e.g., 18:3(n-3) or 22:6(n-3)) or no effect (e.g., 18:1(n-9), 20:3(n-3)) by others. In contrast, only inhibition by 20:4(n-6) was seen in cultured HeLa cells, suggesting that the intracellular interactions may not be universal in all cell lines. For fatty acids that activate 20:4(n-6) formation, the lag observed when substrate and activator were administered simultaneously was eliminated by preincubation with activator. Maximal activation occurred within 4 h for neuroblastoma and 2 h for glioma; in each cell line activation declined steadily for 10 h after removal of the activator. Inhibition of protein synthesis did not alter activation. As 98% of the fatty acid incorporated was esterified to triacylglycerol or phospholipid and only the triacylglycerol mass expanded, several manipulations to potentially alter the flow of acyl chains between these lipid pools were evaluated using dual-label and pulse-chase experiments. Results suggested that competition between 18:2(n-6) utilization for esterification to phospholipid and the desaturation-chain elongation sequence as well as a more direct and specific interaction of certain fatty acids with the enzymes may influence 20:4(n-6) formation. A model to explain these observations is discussed.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000096:biosynthesis; D002460:Cell Line; D005227:Fatty Acids / Q000494:pharmacology*; D005228:Fatty Acids, Essential / Q000378:metabolism*; D005910:Glioma / Q000378:metabolism*; D006367:HeLa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D001095:Arachidonic Acids; D005227:Fatty Acids; D005228:Fatty Acids, Essential; D008041:Linoleic Acids; D010743:Phospholipids; D014280:Triglycerides; D016718:Arachidonic Acid; D019787:Linoleic Acid