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.
Green
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MD
Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333, USA. MDG4@CIDDPD2.EM.CDC.GOV
Xiao
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L
Lal
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AA
D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry*; D002384:Catalysis; D006420:Hemeproteins / Q000737:chemistry*; D006427:Hemin / Q000737:chemistry; D006893:Hydroxyeicosatetraenoic Acids / Q000737:chemistry*; D010084:Oxidation-Reduction; D010963:Plasmodium falciparum / Q000737:chemistry*
D006420:Hemeproteins; D006893:Hydroxyeicosatetraenoic Acids; D016718:Arachidonic Acid; C020753:hemozoin; D006427:Hemin