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

Summary 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...

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Published in:Molecular microbiology 2006-09, Vol.61 (6), p.1598-1608
Main Authors: Zeuthen, Thomas, Wu, Binghua, Pavlovic‐Djuranovic, Slavica, Holm, Lars M., Uzcategui, Nestor L., Duszenko, Michael, Kun, Jürgen F. J., Schultz, Joachim E., Beitz, Eric
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cited_by cdi_FETCH-LOGICAL-c5715-2078e821fd1ce95c1c5c40cd94de177927c5d8009bc0ea1f7ba76ffe0a1dc93d3
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container_title Molecular microbiology
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creator Zeuthen, Thomas
Wu, Binghua
Pavlovic‐Djuranovic, Slavica
Holm, Lars M.
Uzcategui, Nestor L.
Duszenko, Michael
Kun, Jürgen F. J.
Schultz, Joachim E.
Beitz, Eric
description Summary 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.
doi_str_mv 10.1111/j.1365-2958.2006.05325.x
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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. 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J.</creatorcontrib><creatorcontrib>Schultz, Joachim E.</creatorcontrib><creatorcontrib>Beitz, Eric</creatorcontrib><title>Ammonia permeability of the aquaglyceroporins from Plasmodium falciparum, Toxoplasma gondii and Trypansoma brucei</title><title>Molecular microbiology</title><addtitle>Mol Microbiol</addtitle><description>Summary 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. 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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. 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subjects Amino acids
Ammonia
Ammonia - metabolism
Animals
Aquaglyceroporins - genetics
Aquaglyceroporins - physiology
Biological and medical sciences
Fundamental and applied biological sciences. Psychology
Genetic Complementation Test
Hemoglobin
Membrane Proteins - genetics
Membrane Proteins - physiology
Methylamines - toxicity
Microbiology
Oocytes
Parasitic protozoa
Permeability
Plasmodium falciparum
Plasmodium falciparum - growth & development
Plasmodium falciparum - metabolism
Proteins
Saccharomyces cerevisiae - genetics
Saccharomyces cerevisiae - physiology
Saccharomyces cerevisiae Proteins - genetics
Saccharomyces cerevisiae Proteins - physiology
Toxoplasma - growth & development
Toxoplasma - metabolism
Toxoplasma gondii
Trypanosoma brucei
Trypanosoma brucei brucei - growth & development
Trypanosoma brucei brucei - metabolism
Xenopus laevis
title Ammonia permeability of the aquaglyceroporins from Plasmodium falciparum, Toxoplasma gondii and Trypansoma brucei
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