Arachidonic acid metabolic pathway: Appraisal of differential availability of arachidonic acid and anti-inflammatory drugs to COX-1, COX-2 and 5-LOX enzymes

Abstract

Arachidonic acid metabolic pathway has remarkable contribution in the working of biological systems. Having arachidonic acid as the common substrate; the COX-1, COX-2 and 5-LOX channels of this metabolic pathway produce different metabolites which play a significant role in homeostasis, blood clotting, gastrointestinal protection, inflammation and vasoconstriction. The quantity of metabolite produced from the three channels depends upon the expression of each enzyme as well as the affinity of the enzymes for arachidonic acid (the substrate). Here, it is found that the relative affinity of the three enzymes for AA follows the order 5-LOX, COX-1 and COX-2. Based on this trend, the metabolic significance of each channel is rationalized. Moreover, examining the relative interactions of anti-inflammatory drugs like aspirin, diclofenac, indomethacin, celecoxib, zileuton with the three enzymes, the possibility of side effects associated with these drugs was also revisited.