Concerted stimulation and inhibition of desaturation, chain elongation, and esterification of essential fatty acids by cultured neuroblastoma cells.

Abstract

Neuroblastoma (N1E-115) cells in culture rapidly incorporated exogenous fatty acyl chains suspended as albumin complexes in the medium. The essential fatty acids, linoleic (18:2(n - 6)) and linolenic (18:3(n - 3)) acids, were converted to polyunsaturated acids by delta 6 and delta 5 desaturation and chain elongation. The major end products (20:4 from 18:2(n - 6) and 20:5 and 22:5 from 18:3(n - 3)) were preferentially esterified to phospholipids, whereas intermediates were esterified primarily or equally to triacylglycerol. The effects of unlabeled exogenous fatty acids (eg. 40 microM 18:2(n - 6), 18:3(n - 6), 18:3(n - 3), 20:3(n - 6), 20:4(n - 6), trans-18:2(n - 6), 18:1(n - 9), trans-18:1(n - 9), or 16:0) on the conversion of 2 microM [1-(14)C]18:2(n - 6), 18:3(n - 3), 20:3(n - 6), 20:4(n - 6), or 16:0 and on accumulation of products and unaltered substrates in phospholipids and triacylglycerol were examined after incubations of 2-24 h. With [1-(14)C]18:2, formation and esterification of 20:4 to phospholipids was (i) stimulated 4-8-fold by 18:2(n - 6), 20:3(n - 6), or 20:4(n - 6), (ii) inhibited by 18:3(n - 3) or trans-18:2(n - 6), or (iii) unaffected by 18:3(n - 6), 18:1(n - 9), trans-18:1(n - 9), and 16:0. Specific but less marked effects were observed with the other 1-(14)C-substrate acids. Thus, various fatty acids influenced the metabolism of essential fatty acids both at the level of conversion by desaturation and elongation and at esterification to complex lipids by mechanisms specific to individual acids. Product inhibition was not a major feedback mechanism; however, the complement of available fatty acids evidently modulates the acyl chain composition of membrane phospholipids through processes in addition to acyltransferase selectivity. The data support a closely coordinated or concerted enzyme system for directed synthesis of esterified polyunsaturated acyl chains.