Interactions of inhibitors of the lipoxygenase and cyclooxygenase pathways may be due to the existence of a supplementary binding site on soybean lipoxygenase

Abstract

Although both soybean lipoxygenase (LOX) and mammalian cyclooxygenase (CYXOs) are lipoxygenase-types of reaction, only CYOXs are inhibited selectively by NSAIDs whereas soybean and most mammalian LOXs are not affected by these agents (1, 2). Recentlly, KUEHL et al. (3, 4) and other investigators (5–8) demonstrated that most analgesic-antipyretics react with two sites on the CYOX, whereby the reaction of these inhibitors with a new supplementary binding site proved to be a fascinating theory to explain the interaction of weak and potent CYOX inhibitors: drugs interacting more effectively with the supplementary site which is obligatory for inhibitory action than with the catalytic site, i.e. those of weak to moderate anti-CYOX activity, were capable of preventing inhibition of the enzyme by indomethacin or aspirin. Since in contrast to CYOXs soybean and mammalian LOXs are not sensitive to indomethacin or other NSAIDs it was suggested (3–7) that the unique potency of NSAIDs in their inhibitory action of the CYOX is attributable to the presence of the putative supplementary binding site on CYOXs and its absence in LOXs.