A physiochemical mechanism of hemozoin (β-hematin) synthesis by malaria parasite

Abhai K. Tripathi, Babu L. Tekwani, Satyendra K. Garg

Research output: Contribution to journalArticle

Abstract

Malaria parasite homogenate, the lipid extracts, and an unsaturated fatty acid, linoleic acid, which have been shown to promote β-hematin formation in vitro, were used to investigate the mechanism of hemozoin biosynthesis, a distinct metabolic function of the malaria parasite. In vitro β-hematin formation promoted by Plasmodium yoelii homogenate, the lipid extracts, and linoleic acid were blocked by ascorbic acid, reduced glutathione, sodium dithionite, β-mercaptoethanol, dithiothreitol, and superoxide dismutase. Oxidized glutathione did not show any effect. Preoxidized preparations of the lipids extracts or the P. yoelii homogenate failed to catalyze β-hematin formation. Depletion of oxygen in the reaction mixtures also inhibited the lipid-catalyzed β-hematin formation. Under the reaction conditions similar to those used for the in vitro β-hematin formation assay, the antioxidants and reducing agents mentioned above, except the DTT and β-mercaptoethanol, did not cause degradation of heme. β-Hematin formation was also inhibited by p-aminophenol, a free radical chain reaction breaker. Hemozoin biosynthesis within the digestive vacuoles of the malaria parasite may be a lipid-catalyzed physiochemical reaction. An oxidative mechanism may be proposed for lipid-mediated β-hematin formation, which may be mediated by generation of some free radical intermediates of heme.

Original languageEnglish (US)
Pages (from-to)595-601
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume290
Issue number1
DOIs
StatePublished - Jan 1 2002

Keywords

  • Glutathione Plasmodium yoelii
  • Hemozoin
  • Linoleic acid
  • Malaria
  • Plasma
  • Superoxide dismutase
  • β-hematin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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