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Chemical Compound Review

ammonium     azanium

Synonyms: Ammonium(+), Ammonium ion, Ammonium(1+), nitrogen(1+), Ammonia ion, ...
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Disease relevance of ammonium

  • The cleavage products generated from other E. coli tRNA precursors by the KB cell activity are identical in size to those produced by RNAase P. The KB cell endoribonuclease requires Mg2+ and a monovalent cation (Na+, K+, or NH4+) for function [1].
  • Futile transmembrane NH4(+) cycling: a cellular hypothesis to explain ammonium toxicity in plants [2].
  • Bovine lymphosarcoma tissue has been extracted with low- and high-salt buffers [0.05 M Tris-C1 plus or minus 0.3 M (NH4) 2S04] [3].
  • The principal initial product of metabolism of 13N-labeled ammonium by Anabaena cylindrica grown with either NH4+ or N2 as nitrogen source is amide-labeled glutamine [4].
  • The enzyme synthesizes a group of psi residues in the anticodon region of various hisT- isoacceptors and behaves like a eukaryotic homologue of Salmonella tRNA psi synthase I. The thymus enzyme requires a thiol and a monovalent cation (NH4+ or K+) for optimum activity; no energy sources or cofactors are required [5].

High impact information on ammonium

  • Single amino-acid substitutions in H5, the fifth hydrophobic region, enhanced the passage of NH4+ and Rb+, ions with diameters larger than K+, without compromising the ability of the channel to exclude the smaller cation, Na+ [6].
  • The NH4+ conductance distinct from the K+ conductance has been suggested to exist in the proximal tubule, MAL cell, and Xenopus oocyte [7].
  • In the HBC cell, 10 mM Ba2+ in the bath equally suppressed both delta VBK+ and delta VBNH4+, whereas in the LBC cell it suppressed delta VBK+ with a small effect on delta VBNH4+, indicating that NH4+ is transported via a pathway distinct from Ba(2+)-sensitive K+ conductance [7].
  • At 37 degrees C, the transfer of bound ligand to lysosomes was followed by degradation, inhibited by NH4+ [8].
  • O2- generation stimulated by opsonized zymosan or phorbol myristate acetate, by monocytes or monocyte-derived macrophages, and phagocytosis of opsonized zymosan by J774.2 macrophages, showed dependence on external Na+ only if these cells had been pre-treated with NH4+ [9].

Chemical compound and disease context of ammonium

  • In order to determine the effects of acetate on signs and symptoms of hypoglycemic seizures, Swiss Webster albino mice were injected intraperitoneally with solutions of NaCl, NaHCO3, NH4Cl, Na-acetate, or NH4-acetate, followed by subcutaneous injection of 7 U of insulin/kg body wt [10].
  • The NH4+ absorption rate in Henle's loop is increased in chronic metabolic acidosis (CMA) and potassium depletion (KD), which may be secondary to the increased NH4+ concentration in luminal fluid and/or to an increased NH4+ absorptive capacity of MTAL [11].
  • We have detected by nucleotide analog interference mapping (NAIM) purine N7 functional groups in Escherichia coli RNase P RNA that are important for tRNA binding under moderate salt conditions (0.1 M Mg2+, 0.1 M NH4+) [12].
  • This study was designed to evaluate the effect of ammonia (NH3/NH4+) as a regulator of kidney cell hypertrophy and also kidney cell proliferation [13].
  • Selenomonas ruminantium was found to possess two pathways for NH4+ assimilation that resulted in net glutamate synthesis [14].

Biological context of ammonium

  • A binding site for K+ and NH4+ activators was found near the beta-barrel centre [15].
  • The addition of NH4+ to yeast cells growing on l-proline induced rapid ubiquitination, endocytosis, and vacuolar degradation of the plasma membrane protein Gap1 [16].
  • A capillary chemotaxis assay revealed that among a wide range of inorganic and organic chemicals, only ammonium ion (NH4+) could serve as an attractant of Chlamydomonas reinhardtii [17].
  • This intermediate partitions between harmless hydrolysis to pyruvate, NH4+, and active enzyme-pyridoxal-P (catalytic turnover) and suicidal enzyme alkylation by covalent modification with an average partition ratio of 40-60 turnovers/inactivation event/monomer unit of this tetrameric enzyme [18].
  • These findings support a mechanism for CH3NH3+ (NH4+) accumulation which requires K+ antiport (exchange) and is driven by the electrochemical K+ gradient [19].

Anatomical context of ammonium

  • These neutrophils had been pre-treated with NH4+ during a routine purification step [9].
  • NH3 is a small, lipophilic neutral weak base that readily permeates almost all cell membranes, whereas its conjugate weak acid NH4+ generally crosses membranes much more slowly [20].
  • NH4+ crosses many cell membranes via ion channels or on membrane transporters, and cultured mammalian astrocytes and glial cells of bee retina take up NH4+ avidly, in the latter case on a Cl(-)-cotransporter selective for NH4+ over K+ [21].
  • Two domains, Nervy-homology(NH) 2 and NH4, have been implicated in the recruitment of corepressors by AML1-ETO, but the relative roles of NH2 and NH4 vary in different cell lines and have not been examined in nonimmortalized cells [22].
  • Thus, in contrast with internal H+, which interacts at both transport and activator sites, external H+ interacts with the renal microvillus membrane Na+-H+ exchanger at a single site, namely the external transport site, where H+, Na+, Li+, NH4+, and amiloride all compete for binding [23].

Associations of ammonium with other chemical compounds

  • Although it has been demonstrated that Mn2+ and Mg2+ can influence the activity of glutamine synthetase in various organisms, there is little information concerning the effects of these cations on the activity of this enzyme in soil microorganisms or on ability of these microorganisms to assimilate NO3- and NH4+ [24].
  • When grown at low concentrations of (NH4)+ (< or = 2 mM), mutant strains of S. typhimurium that lack GOGAT and therefore are dependent on GDH have a low glutamate pool and grow slowly; we now demonstrate that they have a low K+ pool [25].
  • We assessed apical- vs. basolateral-membrane transport of NH3/NH4+ by using fluorescent dyes and digital imaging to monitor intracellular pH of microvacuolated crypt cells as well as luminal pH [20].
  • Although their products are required for transport of the ammonium analogue methylammonium in washed cells, only in Saccharomyces cerevisiae have they been shown to be necessary for growth at low NH4+ concentrations [26].
  • Furthermore, NH4+ depolarizes neurons to a variable degree, without consistently changing membrane resistance, probably by reducing [K+]i. A decrease in EK+ may also be responsible for decreasing the effectiveness of the outward chloride pump, thus explaining the well known inhibitory effect of NH4+ on the hyperpolarizing IPSP [27].

Gene context of ammonium

  • We recently reported the first characterization of an NH4+ transport protein (Mep1p) in Saccharomyces cerevisiae [28].
  • The Mep2 protein displays the highest affinity for NH4+ (Km, 1 to 2 microM), followed closely by Mep1p (Km, 5 to 10 microM) and finally by Mep3p, whose affinity is much lower (Km, approximately 1.4 to 2.1 mM) [28].
  • These single site mutations gave rise to Rb+- and NH4(+)-selective channels with Rb+ and NH4+ currents that were approximately 10-13-fold greater in amplitude than K+ currents, whereas the NH4+ to K+ current amplitude ratio of wild type KAT1 was 0.28 [29].
  • The defect in spermidine transport was more pronounced in NH4(+)- than proline-grown npr1 cells, suggesting that NPR1 protects against nitrogen catabolite repression of polyamine uptake activity [30].
  • Adding NH4+ to the medium triggers inactivation and degradation of the permease via a regulatory process involving Npi1p/Rsp5p, a ubiquitin-protein ligase [31].

Analytical, diagnostic and therapeutic context of ammonium

  • The reacidification during NH4+ perfusion was inhibited 30.2 +/- 7.4% by DIDS [32].
  • An I.V. glucose tolerance test was performed in 3 groups of 15 rats 60 min after the beginning of a 95 min infusion of either a 2 ml isotonic NaCl solution (control group) or ammonium acetate solutions at low (0.50 mumol/kg/min. NH4+) or high doses (1.70 mumol/kg/min NH4+) [33].
  • The structural and compositional evolution of four members of the ANbWO(6) (A = NH4+, Rb+, H+, K+) defect pyrochlore family have been studied as a function of pressure up to 7 GPa, using a diamond anvil cell and monochromatic synchrotron X-ray powder diffraction [34].
  • Antibody against PR-AMP was purified 53-fold from serum by (NH4) 2SO4 precipitation, and BSA-Sepharose 4B, DEAE-cellulose and (PR-AMP)-BSA-Sepharose 4B column chromatographies [35].
  • Absolute rates of H+ efflux could be calculated from the Nao+-induced delta pHi using a buffering capacity of 25 mmol X liter-1 X pH-1, measured by titration of intact cells with NH4+ [36].


  1. Identification of a ribonuclease P-like activity from human KB cells. Koski, R.A., Bothwell, A.L., Altman, S. Cell (1976) [Pubmed]
  2. Futile transmembrane NH4(+) cycling: a cellular hypothesis to explain ammonium toxicity in plants. Britto, D.T., Siddiqi, M.Y., Glass, A.D., Kronzucker, H.J. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  3. RNA polymerase isolated from bovine lymphosarcoma by sequential low- and high-salt extraction. Keshgegian, A.A., Austin, G.E., Meltzer, S.M., Furth, J.J. Cancer Res. (1975) [Pubmed]
  4. The pathways of assimilation of 13NH4+ by the cyanobacterium, Anabaena cylindrica. Meeks, J.C., Wolk, C.P., Thomas, J., Lockau, W., Shaffer, P.W., Austin, S.M., Chien, W.S., Galonsky, A. J. Biol. Chem. (1977) [Pubmed]
  5. Purification and properties of a mammalian tRNA pseudouridine synthase. Green, C.J., Kammen, H.O., Penhoet, E.E. J. Biol. Chem. (1982) [Pubmed]
  6. Alteration of ionic selectivity of a K+ channel by mutation of the H5 region. Yool, A.J., Schwarz, T.L. Nature (1991) [Pubmed]
  7. Cellular heterogeneity of ammonium ion transport across the basolateral membrane of the hamster medullary thick ascending limb of Henle's loop. Tsuruoka, S., Takeda, M., Yoshitomi, K., Imai, M. J. Clin. Invest. (1993) [Pubmed]
  8. Effects of recombinant tumor necrosis factor on proliferation and differentiation of leukemic and normal hemopoietic cells in vitro. Relationship to cell surface receptor. Peetre, C., Gullberg, U., Nilsson, E., Olsson, I. J. Clin. Invest. (1986) [Pubmed]
  9. Transmembrane signaling: an ion-flux-independent model for signal transduction by complexed Fc receptors. Pfefferkorn, L.C. J. Cell Biol. (1984) [Pubmed]
  10. Effect of acetate on hypoglycemic seizures in mice. Urion, D., Vreman, H.J., Weiner, M.W. Diabetes (1979) [Pubmed]
  11. Expression of rat thick limb Na/H exchangers in potassium depletion and chronic metabolic acidosis. Laghmani, K., Richer, C., Borensztein, P., Paillard, M., Froissart, M. Kidney Int. (2001) [Pubmed]
  12. Purine N7 groups that are crucial to the interaction of Escherichia coli rnase P RNA with tRNA. Heide, C., Feltens, R., Hartmann, R.K. RNA (2001) [Pubmed]
  13. Ammonium chloride alters renal tubular cell growth and protein turnover. Rabkin, R., Palathumpat, M., Tsao, T. Lab. Invest. (1993) [Pubmed]
  14. Ammonia assimilation and glutamate formation in the anaerobe Selenomonas ruminantium. Smith, C.J., Hespell, R.B., Bryant, M.P. J. Bacteriol. (1980) [Pubmed]
  15. Novel active site in Escherichia coli fructose 1,6-bisphosphate aldolase. Blom, N.S., Tétreault, S., Coulombe, R., Sygusch, J. Nat. Struct. Biol. (1996) [Pubmed]
  16. A nonconserved Ala401 in the yeast Rsp5 ubiquitin ligase is involved in degradation of Gap1 permease and stress-induced abnormal proteins. Hoshikawa, C., Shichiri, M., Nakamori, S., Takagi, H. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  17. Chemotactic responses of Chlamydomonas reinhardtii. Sjoblad, R.D., Frederikse, P.H. Mol. Cell. Biol. (1981) [Pubmed]
  18. Mechanism-based inactivation of serine transhydroxymethylases by D-fluoroalanine and related amino acids. Wang, E.A., Kallen, R., Walsh, C. J. Biol. Chem. (1981) [Pubmed]
  19. Characterization of ammonium (methylammonium)/potassium antiport in Escherichia coli. Jayakumar, A., Epstein, W., Barnes, E.M. J. Biol. Chem. (1985) [Pubmed]
  20. An apical permeability barrier to NH3/NH4+ in isolated, perfused colonic crypts. Singh, S.K., Binder, H.J., Geibel, J.P., Boron, W.F. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  21. Ammonium in nervous tissue: transport across cell membranes, fluxes from neurons to glial cells, and role in signalling. Marcaggi, P., Coles, J.A. Prog. Neurobiol. (2001) [Pubmed]
  22. Cooperative function of Aml1-ETO corepressor recruitment domains in the expansion of primary bone marrow cells. Hug, B.A., Lee, S.Y., Kinsler, E.L., Zhang, J., Lazar, M.A. Cancer Res. (2002) [Pubmed]
  23. Interaction of external H+ with the Na+-H+ exchanger in renal microvillus membrane vesicles. Aronson, P.S., Suhm, M.A., Nee, J. J. Biol. Chem. (1983) [Pubmed]
  24. Effects of Mn2+ and Mg2+ on assimilation of NO3- and NH4+ by soil microorganisms. McCarty, G.W., Bremner, J.M. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  25. Glutamate is required to maintain the steady-state potassium pool in Salmonella typhimurium. Yan, D., Ikeda, T.P., Shauger, A.E., Kustu, S. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  26. Ammonia acquisition in enteric bacteria: physiological role of the ammonium/methylammonium transport B (AmtB) protein. Soupene, E., He, L., Yan, D., Kustu, S. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  27. Effect of ammonium ions on synaptic transmission in the mammalian central nervous system. Szerb, J.C., Butterworth, R.F. Prog. Neurobiol. (1992) [Pubmed]
  28. A family of ammonium transporters in Saccharomyces cerevisiae. Marini, A.M., Soussi-Boudekou, S., Vissers, S., Andre, B. Mol. Cell. Biol. (1997) [Pubmed]
  29. Identification of strong modifications in cation selectivity in an Arabidopsis inward rectifying potassium channel by mutant selection in yeast. Uozumi, N., Gassmann, W., Cao, Y., Schroeder, J.I. J. Biol. Chem. (1995) [Pubmed]
  30. The spermidine transport system is regulated by ligand inactivation, endocytosis, and by the Npr1p Ser/Thr protein kinase in Saccharomyces cerevisiae. Kaouass, M., Gamache, I., Ramotar, D., Audette, M., Poulin, R. J. Biol. Chem. (1998) [Pubmed]
  31. A C-terminal di-leucine motif and nearby sequences are required for NH4(+)-induced inactivation and degradation of the general amino acid permease, Gap1p, of Saccharomyces cerevisiae. Hein, C., André, B. Mol. Microbiol. (1997) [Pubmed]
  32. DIDS-sensitive pHi regulation in single rat cardiac myocytes in nominally HCO3-free conditions. Wu, M.L., Tsai, M.L., Tseng, Y.Z. Circ. Res. (1994) [Pubmed]
  33. Diabetogenic effect and inhibition of insulin secretion induced in normal rats by ammonium infusions. Schlienger, J.L., Imler, M., Stahl, J. Diabetologia (1975) [Pubmed]
  34. Pressure-induced cation migration and volume expansion in the defect pyrochlores ANbWO6 (A = NH4+, Rb+, H+, K+). Barnes, P.W., Woodward, P.M., Lee, Y., Vogt, T., Hriljac, J.A. J. Am. Chem. Soc. (2003) [Pubmed]
  35. Formation and characterization of antibody against 2'-(5"-phosphoribosyl)-5' AMP, the monomer form of poly(adenosine diphosphate ribose). Sakura, H., Miwa, M., Kanai, Y., Matsushima, T., Sugimura, T. Nucleic Acids Res. (1978) [Pubmed]
  36. Cytoplasmic pH regulation in thymic lymphocytes by an amiloride-sensitive Na+/H+ antiport. Grinstein, S., Cohen, S., Rothstein, A. J. Gen. Physiol. (1984) [Pubmed]
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