FORMATION OF HYDROXYEICOSATETRAENOIC ACIDS FROM HEMOZOIN-CATALYZED OXIDATION OF ARACHIDONIC-ACID

Hemozoin, a heme byproduct of hemoglobin digestion by malaria parasite s, is released into the blood stream of the host upon lysing of infect ed erythrocytes. Since heme-compounds are potent catalysts of lipid pe roxidation, we evaluated the catalytic ability of Plasmodium falciparu m-derived hemozoin to oxidize arachidonic acid to hydroxyeicosatetraen oic acids (HETEs). Hemozoin, beta-hematin, and hematin all catalyzed t he 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 pre dominant isomer generated by hemozoin catalysis while 5-HETE was the m ajor product formed by hematin catalysis. Since HETEs are important va soactive mediators, the non-enzymatic oxidation of arachidonic acid by hemozoin catalysis may contribute to some of the pathophysiology asso ciated with severe and cerebral malaria. Copyright (C) 1996 Elsevier S cience B.V.