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Open Life Sciences

formerly Central European Journal of Biology

Editor-in-Chief: Ratajczak, Mariusz

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Volume 4, Issue 3


Volume 10 (2015)

Brain monoamine oxidase A in hyperammonemia is regulated by NMDA receptors

Elena Kosenko
  • Laboratory of Metabolic Modelling and Bioinformatics, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290, Pushchino, Russia
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/ Yury Kaminsky
  • Laboratory of Metabolic Modelling and Bioinformatics, Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, 142290, Pushchino, Russia
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Published Online: 2009-07-26 | DOI: https://doi.org/10.2478/s11535-009-0016-2


Mitochondrial enzyme monoamine oxidase A (MAO-A) generates hydrogen peroxide (H2O2) and is up-regulated by Ca2+ and presumably by ammonia. We hypothesized that MAO-A may be under the control of NMDA receptors in hyperammonemia. In this work, the in vivo effects of single dosing with ammonia and NMDA receptor antagonist MK-801 and the in vitro effect of Ca2+ on MAO-A activity in isolated rat brain mitochondria were studied employing enzymatic procedure. Intraperitoneal injection of rats with ammonia led to an increase in MAO-A activity in mitochondria indicating excessive H2O2 generation. Calcium added to isolated mitochondria stimulated MAO-A activity by as much as 84%. MK-801 prevented the in vivo effect of ammonia, implying that MAO-A activation in hyperammonemia is mediated by NMDA receptors. These data support the conclusion that brain mitochondrial MAO-A is regulated by the function of NMDA receptors. The enzyme can contribute to the oxidative stress associated with hyperammonemic conditions such as encephalopathy and Alzheimer’s disease. The attenuation of the oxidative stress highlights MAO-A inactivation and NMDA receptor antagonists as sources of novel avenues in the treatment of mental disorders.

Keywords: Ammonia; Hyperammonemia; Monoamine oxidase; NMDA receptor; Brain mitochondria; Hydrogen peroxide

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About the article

Published Online: 2009-07-26

Published in Print: 2009-09-01

Citation Information: Open Life Sciences, Volume 4, Issue 3, Pages 321–326, ISSN (Online) 2391-5412, DOI: https://doi.org/10.2478/s11535-009-0016-2.

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© 2009 Versita Warsaw. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

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