Close agreement between rates of condensation and overall chain elongation have been observed with eight octadecadienoic isomers in which the double bonds were moved from the 4,7- to the 11,14-positions. The specific activities for overall chain elongation of 7,10-and 6,9-octadecadienoic acids were, respectively, 5.20 and 2.89 nmol product min-1 mg-1 rat liver microsomal protein, while the specific activities for the other six isomers were all below 0.84. The specific activities for both the β-hydroxyacyl-CoA dehydrase and 2-trans-enoyl-CoA reductase reactions were measured using the appropriate substrates required in chain elongating 5,8-, 7,10-, and 8,11-octadecadienoic acids. Although these rates were not as markedly influenced by structural modification, they were all much greater than the initial reaction thus implicating condensation as rate limiting. Both 7- and 9-octadecenoic acids were poor substrates for overall chain elongation even though both 6,9- and 7,10-octadecadienoic acids readily condensed with malonyl-CoA. The rate of overall elongation increased for 7,10-unsaturated acids as the chain length of the primer was extended from 14- to 18-carbons, however, 7,10-eicosadienoic acid was virtually inactive. When rates of overall chain elongation were measured with an isomeric series of six octadecatrienoic acids in which the double bonds were shifted from the 4,7,10- to the 9,12,15-positions, only the 5,8,11-, 6,9,12-, and 7,10,13-isomers were readily chain elongated. Again, as with the octadecadienoic acid isomers the best substrate had the first double bond at position 7. Again the rate of chain elongation was chain length dependent since both 5,8,11- and 7,10,13-eicosatrienoic acid were chain elongated at lower rates than were their 18 carbon analogs. When the substrates were grouped according to common terminal structures no single feature was identifiable which dictated whether a primer would readily be chain elongated. Our findings are thus most consistent with a high degree of substrate specificity for condensation which involves carboxyl recognition but is also dictated both by chain length, double-bond positions, and degree of unsaturation. © 1979.
