Ammonia permeability of the aquaglyceroporins from Plasmodium falciparum, Toxoplasma gondii and Trypansoma brucei

Thomas Zeuthen, Binghua Wu, Slavica Pavlovic-Djuranovic, Lars M. Holm, Nestor L. Uzcategui, Michael Duszenko, Jürgen F.J. Kun, Joachim E. Schultz, Eric Beitz

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

Abstract

Plasmodium falciparum uses amino acids from haemoglobin degradation mainly for protein biosynthesis. Glutamine, however, is mostly oxidized to 2-oxoglutarate to restore NAD(P)H + H+. In this process two molecules of ammonia are released. We determined an ammonia production of 9 mmol h -1 per litre of infected red blood cells in the early trophozoite stage. External application of ammonia yielded a cytotoxic IC50 concentration of 2.8 mM. As plasmodia cannot metabolize ammonia it must be exported. Yet, no biochemical or genomic evidences exist that plasmodia possess classical ammonium transporters. We expressed the P. falciparum aquaglyceroporin (PfAQP) in Xenopus laevis oocytes and examined whether it may serve as an exit pathway for ammonia. We show that injected oocytes: (i) acidify the medium due to ammonia uptake, (ii) take up [14C]methylamine and [ 14C]formamide, (iii) swell in solution with formamide and acetamide and (iv) display an ammonia-induced NH4+-dependent clamp current. Further, a yeast strain lacking the endogenous aquaglyceroporin (Fps1) is rescued by expression of PfAQP which provides for the efflux of toxic methylamine. Ammonia permeability was similarly established for the aquaglyceroporins from Toxoplasma gondii and Trypanosoma brucei. Apparently, these aquaglyceroporins are important for the release of ammonia derived from amino acid breakdown.

Original languageEnglish
Pages (from-to)1598-1608
Number of pages11
JournalMolecular Microbiology
Volume61
Issue number6
DOIs
StatePublished - Sep 2006

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