Formation of hydroxyeicosatetraenoic acids from hemozoin-catalyzed oxidation of arachidonic acid

Hemozoin, a heme byproduct of hemoglobin digestion by malaria parasites, is released into the blood stream of the host upon lysing of infected erythrocytes. Since heme-compounds are potent catalysts of lipid peroxidation, we evaluated the catalytic ability of Plasmodium falciparum-derived hemozoin to oxidize arachidonic acid to hydroxyeicosatetraenoic acids (HETEs). Hemozoin, beta-hematin, and hematin all catalyzed the formation of 15-, 12- and 5-HETE as major products. Although there were no significant differences in total amounts of HETEs generated by hemozoin relative to hematin or beta-hematin, there were significant differences in the proportions of certain isomers. 15-HETE was the predominant isomer generated by hemozoin catalysis while 5-HETE was the major product formed by hematin catalysis. Since HETEs are important vasoactive mediators, the non-enzymatic oxidation of arachidonic acid by hemozoin catalysis may contribute to some of the pathophysiology associated with severe and cerebral malaria. Copyright (C) 1996 Elsevier Science B.V.