Oxygenation of arachidonic acid under hypoxic conditions: some methodological aspects and possible biological relevance

Hypoxia has been shown to alter the arachidonic acid cascade in various tis sues. Once released, arachidonic acid is immediately metabolized through li poxygenase (LOX) and/or cyclooxygenase (COX) pathways. LOX incorporates one molecule of oxygen at various carbon atoms of arachidonic acid, yeilding r espective hydroperoxy-eicosatetraenoic acids, while COX inserts two molecul es of oxygen into the fatty acid substrate, producing prostaglandin Ga Thus , molecular oxygen, as the second substrate of the LOX- and COX-mediated ar achidonate oxygenation, is required ai the first step of the arachidonic ac id cascade. Previously, LOXs and COXs of mammalian origin have been broadly studied wish regard to their fatty acid substrate specificity, and recentl y, their affinities to molecular. oxygen were evaluated. Data oi the oxygen dependency of these enzymes may help to understand their functions and an involvement of the respective arachidonic acid-derived metabolites in cellu lar biology. That may elucidate mechanisms of hypoxia-induced alterations o f tissue functions mediated hy various eicosanoids. Findings about the affi nities of the arachidonate oxygenases for molecular oxygen together with th e knowledge of oxygen concentration in the tissue are used as basic informa tion for the in vivo implication of eicosanoid synthesis under hypoxic cond itions.