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Adenosine and Energy Metabolism—Relationship to Brain Bioenergetics

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Adenosine

Abstract

The brain is one of the most metabolically active organs in the body, but because it has a limited capacity to store bioenergetic molecules it requires a continuous supply of oxygen and energy. In order to meet the high metabolic needs of the brain, the blood–brain barrier selectively expresses specific transport systems including glucose transporters and monocarboxylic acid transporters that transport lactate and ketone bodies. As a universal energy source, adenosine triphosphate (ATP) drives biological reactions essential for brain functions, and loss of such cellular energy results in profound abnormalities in brain function. The high-energy phosphate bonds of ATP are rather labile and thus energy inherent in ATP is readily released when ATP is hydrolyzed sequentially to ADP, AMP, and finally adenosine. Although each of these molecules serves different functions and can activate different signaling pathways, our focus here is on adenosine and brain energy metabolism. Under basal conditions, brain levels of adenosine are nearly 10,000-fold lower than ATP. Therefore, unnoticeable and possibly physiologically irrelevant decreases in ATP levels can result in dramatic and physiologically relevant rises in adenosine levels. As brain energy levels drop, adenosine levels rise to adjust brain energy supply and to retaliate against an external stimulus that would otherwise cause excessive ATP breakdown. These actions of adenosine are mediated by adenosine receptors located on target cells including neurons, glial cells, and brain endothelial cells. A critical issue in studying brain bioenergetics is the precise and accurate measurement of levels of ATP and its metabolites including adenosine. Because these molecules can be degraded rapidly, it is challenging to make such measurements. Essential components in the correct assessment of brain energetics should include justifying carefully the methodology used and putting the data in the context of what is already known about brain energy metabolism.

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Acknowledgments

The work currently conducted in our laboratories is supported by 2P20RR0017699 from the NCRR, a component of the NIH, and by R01NS069597.

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  1. Department of Pharmacology, Physiology and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, 501 N. Columbia Road, Grand Forks, ND, 58202, USA

    Xuesong Chen, Liang Hui & Jonathan D. Geiger

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  1. Xuesong Chen
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  2. Liang Hui
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Correspondence to Jonathan D. Geiger .

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  1. Trinity College, 300 Summit Street, LSC 208, Hartford, 06106, USA

    Susan Masino

  2. Legacy Research Institute, Portland, OR,, 1225 NE 2nd Avenue, Portland, 97232, USA

    Detlev Boison

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Chen, X., Hui, L., Geiger, J.D. (2013). Adenosine and Energy Metabolism—Relationship to Brain Bioenergetics. In: Masino, S., Boison, D. (eds) Adenosine. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3903-5_3

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