Dihydroxyacetone and methylglyoxal as permeants of the Plasmodium aquaglyceroporin inhibit parasite proliferation

Slavica Pavlovic-Djuranovic, Jürgen F.J. Kun, Joachim E. Schultz, Eric Beitz

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

The aquaglyceroporin of Plasmodium falciparum (PfAQP) is a bi-functional channel with permeability for water and solutes. Its functions supposedly are in osmotic protection of parasites and in facilitation of glycerol permeation for glycerolipid biosynthesis. Here, we show PfAQP permeability for the glycolysis-related metabolites methylglyoxal, a cytotoxic byproduct, and dihydroxyacetone, a ketotriose. AQP3, the red cell aquaglyceroporin, also passed dihydroxacetone but excluded methylglyoxal. Proliferation of malaria parasites was inhibited by methylglyoxal with an IC50 around 200 μM. Surprisingly, also dihydroxyacetone, which is an energy source in human cells, was antiproliferative in chloroquine-sensitive and resistant strains with an IC50 around 3 mM. We expressed P. falciparum glyceraldehyde 3-phosphate dehydrogenase (PfGAPDH) to examine whether it is inhibited by either carbonyl compound. Methylglyoxal did not affect PfGAPDH on incubation with 2.5 mM for 20 h. Treatment with 2.5 mM dihydroxyacetone, however, abolished PfGAPDH activity within 6 h. Aquaglyceroporin permeability for glycolytic metabolites may thus be of physiological significance.

Original languageEnglish
Pages (from-to)1012-1017
Number of pages6
JournalBiochimica et Biophysica Acta - Biomembranes
Volume1758
Issue number8
DOIs
StatePublished - Aug 2006
Externally publishedYes

Keywords

  • Aquaglyceroporin
  • Dihydroxyacetone
  • Glyceraldehyde 3-phosphate dehydrogenase
  • Malaria
  • Methylglyoxal
  • Plasmodia

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