CHAIN ELONGATION OF POLYUNSATURATED FATTY-ACIDS BY VASCULAR ENDOTHELIAL-CELLS - STUDIES WITH ARACHIDONATE ANALOGS

This study has utilized radiolabeled analogues of arachidonic acid to study the substrate specificity of elongation of long-chain polyunsaturated fatty acids. Human umbilical vein endothelial cells were incubated for 2-72 hr in medium supplemented with 0.9-2.6 μM [14C]fatty acid, and cellular glycerolipids were analyzed by gas-liquid chromatography with radioactivity detection. Elongation of naturally occurring C20 polyunsaturated fatty acids occurred with eicosapentaenoate (20:5(n-3))>Mead acid (20:3(n-9))>arachidonate (20:4(n-6)). Chain length markedly influenced the extent of elongation of 5,8,11,14-tetraenoates (18:4>19:4>20:4>21:4); effects of initial double bond position were also observed (6,9,12,15-20:4>4,7,10,13-20:4. Neither 5,8,14- nor 5,11,14-20:3 was elongated to the extent of 5,8,11-20:3. Differences between polyunsaturated fatty acids were observed both in the initial rates and in the maximal percentages of elongation, suggesting that the content of cellular C20 and C22 fatty acids may represent a balance between chain elongation and retroconversion. Umbilical vein endothelial cells do not exhibit significant desaturation of either 22:4(n-6) or 22:5(n-3). By contrast, incubation with 5,8,11,14-[14C]18:4(n-4) resulted in formation of both [14C]20:5(n-4) and [14C]22:5(n-4). The respective time courses for the appearances of [14C]22:5(n-4) and [14C]20:5(n-5) suggests Δ6 desaturation of [14C]22:4(n-4) rather than Δ4 desaturation of [14C]20:4(n-4). © 1990 American Oil Chemists' Society.