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The mammalian purine salvage pathway as an exploitable route for cerebral bioenergetic support after brain injury
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Gessner, Philipp, Lum, Jenni and Frenguelli, Bruno G. (2023) The mammalian purine salvage pathway as an exploitable route for cerebral bioenergetic support after brain injury. Neuropharmacology, 224 . 109370. doi:10.1016/j.neuropharm.2022.109370 ISSN 0028-3908.
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Official URL: https://doi.org/10.1016/j.neuropharm.2022.109370
Abstract
Purine-based molecules play ancient, fundamental, and evolutionarily-conserved roles across life on Earth, ranging from DNA and RNA, to the universal energy currency, ATP. In mammals, the two primary routes for the synthesis of the adenine nucleotides ATP, ADP and AMP, and, as a consequence, the major bioactive metabolite adenosine, are the de novo purine biosynthesis (DNPB) pathway, and the purine salvage pathway (PSP). Of the two, the PSP dominates in both the mammalian brain and heart. This is because the PSP utilizes the breakdown products of ATP, occasioned by the high energy demands of these organs, to rapidly regenerate adenine nucleotides. This resynthesis route, while efficient and energetically favourable, leaves these organs vulnerable to loss of salvageable metabolites, with the potential for protracted depletion of the means to synthesize ATP, and the ability to deploy neuro- and cardioprotective adenosine. Having previously shown that hippocampal cellular ATP and adenosine release can be increased by supplying substrates for the PSP (d-ribose and adenine), we now explore the expression of DNPB and PSP enzymes in hippocampal neurons and astrocytes based on available transcriptomic data. We find that key enzymes of the PSP are expressed at higher levels than those in the DNPB pathway, and that PSP enzymes are expressed at higher levels in neurons than in astrocytes. These data reflect the importance of the PSP in the mammalian brain and imply that pharmacological targeting of the PSP may be particularly beneficial to neurons at times of metabolic stress.
| Item Type: | Journal Article | ||||||||
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| Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine |
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| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||
| SWORD Depositor: | Library Publications Router | ||||||||
| Library of Congress Subject Headings (LCSH): | Purines -- Metabolism, Purines -- Synthesis, Neurons, Astrocytes, Cerebrovascular disease, Ischemia, Adenosine, Ribose, Adenine | ||||||||
| Journal or Publication Title: | Neuropharmacology | ||||||||
| Publisher: | Elsevier | ||||||||
| ISSN: | 0028-3908 | ||||||||
| Official Date: | 15 February 2023 | ||||||||
| Dates: |
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| Volume: | 224 | ||||||||
| Number of Pages: | 12 | ||||||||
| Article Number: | 109370 | ||||||||
| DOI: | 10.1016/j.neuropharm.2022.109370 | ||||||||
| Status: | Peer Reviewed | ||||||||
| Publication Status: | Published | ||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||
| Date of first compliant deposit: | 9 January 2023 | ||||||||
| Date of first compliant Open Access: | 10 January 2023 | ||||||||
| RIOXX Funder/Project Grant: |
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