Heme—Polyenoic Acid Interaction and Prostaglandin Synthesis

  • Gundu H. R. Rao
  • James G. White
Part of the GWUMC Department of Biochemistry Annual Spring Symposia book series (GWUN)


Yoshimoto and associates (1970) were first to demonstrate that heme is required for enhancing the activity of prostaglandin synthetase enzymes. Ogino et al. (1978) found very little iron in purified endoperoxide synthetase but found that the enzyme required metalloporphyrins for its activity. Ultrastructural studies from our laboratory using an iron-reactive drug, diaminobenzidine, reported that enzymes involved in endoperoxide generation are localized in the dense tubular system (DTS) of human platelets. The fact that heme iron acts as a catalyst for the isolated enzymes and that heme-complexing compounds react with these enzymes in the platelet DTS prompted us to evaluate the role of iron and heme in arachidonic acid oxidation. Using a cell-free system, we showed that ferrous iron and heme can induce oxidation of polyenoic acids and the extent of oxidation was related to the degree of unsat-uration in the fatty acids. The iron-induced oxidation of fatty acids was not inhib-itable by radical scavengers or by Superoxide dismutase. Heme or iron chelators,as well as several of the known inhibitors of cyclooxygenase, blocked this reaction. Ferrous iron chelators and heme-complexing agents inhibited prostaglandin synthesis as well as platelet function. In vivo studies using a short-acting drug, ibu-profen, and an irreversible inhibitor of cyclooxygenase, aspirin, confirmed our findings that the majority of prostaglandin inhibitors exert their effect by interfering with heme-arachidonic acid interaction. Based on this evidence, we hypothesized that polyenoic acid released from platelet membranes following activation could compete for the heme site and inhibit the conversion of arachidonic acid.


Arachidonic Acid Ferrous Iron Platelet Function Human Platelet Prostaglandin Synthesis 
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Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • Gundu H. R. Rao
    • 1
  • James G. White
    • 1
  1. 1.Department of Laboratory Medicine and Pathology, Medical SchoolUniversity of MinnesotaMinneapolisUSA

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