Incorporation of 5,8,11,14-eicosatetraynoic acid (ETYA) into cell lipids: competition with arachidonic acid for esterification.

5,8,11,14-eicosatetraynoic acid (ETYA), a widely used inhibitor of cyclooxygenase and lipoxygenase, inhibited the incorporation of 14C-arachidonic acid into cell lipids of the murine thymoma EL4 whereas oleic acid had no effect. Inhibition appeared to result from the ability of ETYA to compete with arachidonic acid for esterification enzymes and to be itself incorporated into cell lipids. The positional specificity for ETYA incorporation was similar to that of arachidonic acid. ETYA, but not oleic acid competed with arachidonate for activation by a selective arachidonoyl CoA synthetase in lymphocytes. This may explain in part the apparent specificity of effects seen on incorporation into whole cells. In addition ETYA, unlike other arachidonate analogs tested previously, caused significant inhibition of the nonselective acyl CoA synthetase in lymphocytes. These results are discussed with respect to the use of ETYA to examine the role of intrinsic arachidonic acid metabolism in cellular processes.