EFFECTS OF DOCOSAHEXAENOIC (22-6N-3), TETRACOSAPENTAENOIC (24-5N-3) AND TETRACOSAHEXAENOIC (24-6N-3) ACIDS ON THE DESATURATION AND ELONGATION OF N-3 POLYUNSATURATED FATTY-ACIDS IN TROUT LIVER-MICROSOMES

The effects of long chain n-3 polyunsaturated fatty acids (PUFA) on th e desaturation and elongation systems involved in the conversion of 18 :3n-3 to 24:6n-3 were investigated. Microsomes were prepared from the livers of rainbow trout and incubated with C-14-labelled 18:3n-3 and c ofactors required for elongation and/or desaturation in the presence o f 22:6n-3, 24:5n-3 or 24:6n-3. The formation of 24:6n-3 was significan tly inhibited in the presence of 50 mu M 22:6n-3, 24:5n-3 or 24:6n-3, whereas the amount of radiolabelled 20:5n-3 formed was inhibited by on ly 24:5n-3 or 24:6n-3 at the same concentration. When malonyl-CoA was omitted from the incubation system to allow the measurement of desatur ation in the absence of elongation, the Delta 6 desaturation of C-14-1 8:3n-3 to C-14-18:4n-3 was inhibited by approximately 25% in the prese nce of 24:5n-3 or 24:6n-3 but was not affected by 22:6n-3. The Delta 5 desaturation of C-14-20:4n-3 was not affected by the presence of any of the long chain PUFA and no significant effect of 18:3n-3, 22:6n-3 o r 24:6n-3 on the Delta 6 desaturation of 24:5n-3 to 24:6n-3 was observ ed. To permit the measurement of individual elongation reactions, KCN was included in the incubation medium to inhibit desaturation and C-14 -labelled 18:3n-3, 18:4n-3, 20:4n-3, 20:5n-3 and 22:5n-3 were examined as substrates. 18:4n-3 and 22:5n-3 were more extensively used for elo ngation than 18:3n-3, 20:4n-3 and 20:5n-3. The presence of 22:6n-3, 24 :5n-3 or 24:6n-3 in the incubation system had no effect on any of the specific elongations of any of the substrates examined. It is conclude d that, in the conversion of 18:3n-3 to 24:6n-3 by trout liver microso mes, the Delta 6 desaturation of 18:3n-3 may be subjected to direct fe edback inhibition and that 24:5n-3 may be preferred over 18:3n-3 as a substrate for Delta 6 desaturation. (C) 1998 Elsevier Science B.V.