The double-edged sword: gaining adenosine at the expense of ATP. How to balance the books

Stephanie Zur Nedden, Alexander S. Doney, Bruno G. Frenguelli

    Research output: Chapter in Book/Report/Conference proceedingChapter

    1 Citation (Scopus)

    Abstract

    Under physiological conditions the brain, via the purine salvage pathway, reuses the preformed purine bases hypoxanthine, derived from ATP degradation, and adenine (Ade), derived from polyamine synthesis, to restore its ATP pool. However, the massive degradation of ATP during ischemia, although providing valuable neuroprotective adenosine, results in the accumulation and loss of diffusible purine metabolites and thereby leads to a protracted reduction in the post-ischemic ATP pool size. In vivo, this may both limit the ability to deploy ATP-dependent reparative mechanisms and reduce the subsequent availability of adenosine, whilst in brain slices results in tissue with substantially lower levels of ATP than in vivo. In the present review, we describe the mechanisms by which brain tissue replenishes its ATP, how this can be improved with the clinically tolerated chemicals d-ribose and adenine, and the functional, and potential therapeutic, implications of doing so.

    Original languageEnglish
    Title of host publicationAdenosine: A Key Link between Metabolism and Brain Activity
    PublisherSpringer
    Pages109-129
    Number of pages21
    ISBN (Print)9781461439035, 1461439027, 9781461439028
    DOIs
    Publication statusPublished - 1 Nov 2013

    Fingerprint

    Adenosine
    Adenosine Triphosphate
    Adenine
    Brain
    Hypoxanthine
    Ribose
    Polyamines
    Ischemia
    purine

    Keywords

    • Adenine
    • Adenosine
    • ATP
    • d-Ribose
    • Epilepsy
    • Ischemia
    • Purine salvage
    • Rib/Ade
    • Traumatic brain injury

    Cite this

    Nedden, S. Z., Doney, A. S., & Frenguelli, B. G. (2013). The double-edged sword: gaining adenosine at the expense of ATP. How to balance the books. In Adenosine: A Key Link between Metabolism and Brain Activity (pp. 109-129). Springer . https://doi.org/10.1007/978-1-4614-3903-5_6
    Nedden, Stephanie Zur ; Doney, Alexander S. ; Frenguelli, Bruno G. / The double-edged sword : gaining adenosine at the expense of ATP. How to balance the books. Adenosine: A Key Link between Metabolism and Brain Activity. Springer , 2013. pp. 109-129
    @inbook{cd4871f00d0748c0a58d5e432070b46e,
    title = "The double-edged sword: gaining adenosine at the expense of ATP. How to balance the books",
    abstract = "Under physiological conditions the brain, via the purine salvage pathway, reuses the preformed purine bases hypoxanthine, derived from ATP degradation, and adenine (Ade), derived from polyamine synthesis, to restore its ATP pool. However, the massive degradation of ATP during ischemia, although providing valuable neuroprotective adenosine, results in the accumulation and loss of diffusible purine metabolites and thereby leads to a protracted reduction in the post-ischemic ATP pool size. In vivo, this may both limit the ability to deploy ATP-dependent reparative mechanisms and reduce the subsequent availability of adenosine, whilst in brain slices results in tissue with substantially lower levels of ATP than in vivo. In the present review, we describe the mechanisms by which brain tissue replenishes its ATP, how this can be improved with the clinically tolerated chemicals d-ribose and adenine, and the functional, and potential therapeutic, implications of doing so.",
    keywords = "Adenine, Adenosine, ATP, d-Ribose, Epilepsy, Ischemia, Purine salvage, Rib/Ade, Traumatic brain injury",
    author = "Nedden, {Stephanie Zur} and Doney, {Alexander S.} and Frenguelli, {Bruno G.}",
    year = "2013",
    month = "11",
    day = "1",
    doi = "10.1007/978-1-4614-3903-5_6",
    language = "English",
    isbn = "9781461439035",
    pages = "109--129",
    booktitle = "Adenosine: A Key Link between Metabolism and Brain Activity",
    publisher = "Springer",

    }

    Nedden, SZ, Doney, AS & Frenguelli, BG 2013, The double-edged sword: gaining adenosine at the expense of ATP. How to balance the books. in Adenosine: A Key Link between Metabolism and Brain Activity. Springer , pp. 109-129. https://doi.org/10.1007/978-1-4614-3903-5_6

    The double-edged sword : gaining adenosine at the expense of ATP. How to balance the books. / Nedden, Stephanie Zur; Doney, Alexander S.; Frenguelli, Bruno G.

    Adenosine: A Key Link between Metabolism and Brain Activity. Springer , 2013. p. 109-129.

    Research output: Chapter in Book/Report/Conference proceedingChapter

    TY - CHAP

    T1 - The double-edged sword

    T2 - gaining adenosine at the expense of ATP. How to balance the books

    AU - Nedden, Stephanie Zur

    AU - Doney, Alexander S.

    AU - Frenguelli, Bruno G.

    PY - 2013/11/1

    Y1 - 2013/11/1

    N2 - Under physiological conditions the brain, via the purine salvage pathway, reuses the preformed purine bases hypoxanthine, derived from ATP degradation, and adenine (Ade), derived from polyamine synthesis, to restore its ATP pool. However, the massive degradation of ATP during ischemia, although providing valuable neuroprotective adenosine, results in the accumulation and loss of diffusible purine metabolites and thereby leads to a protracted reduction in the post-ischemic ATP pool size. In vivo, this may both limit the ability to deploy ATP-dependent reparative mechanisms and reduce the subsequent availability of adenosine, whilst in brain slices results in tissue with substantially lower levels of ATP than in vivo. In the present review, we describe the mechanisms by which brain tissue replenishes its ATP, how this can be improved with the clinically tolerated chemicals d-ribose and adenine, and the functional, and potential therapeutic, implications of doing so.

    AB - Under physiological conditions the brain, via the purine salvage pathway, reuses the preformed purine bases hypoxanthine, derived from ATP degradation, and adenine (Ade), derived from polyamine synthesis, to restore its ATP pool. However, the massive degradation of ATP during ischemia, although providing valuable neuroprotective adenosine, results in the accumulation and loss of diffusible purine metabolites and thereby leads to a protracted reduction in the post-ischemic ATP pool size. In vivo, this may both limit the ability to deploy ATP-dependent reparative mechanisms and reduce the subsequent availability of adenosine, whilst in brain slices results in tissue with substantially lower levels of ATP than in vivo. In the present review, we describe the mechanisms by which brain tissue replenishes its ATP, how this can be improved with the clinically tolerated chemicals d-ribose and adenine, and the functional, and potential therapeutic, implications of doing so.

    KW - Adenine

    KW - Adenosine

    KW - ATP

    KW - d-Ribose

    KW - Epilepsy

    KW - Ischemia

    KW - Purine salvage

    KW - Rib/Ade

    KW - Traumatic brain injury

    UR - http://www.scopus.com/inward/record.url?scp=84930327421&partnerID=8YFLogxK

    U2 - 10.1007/978-1-4614-3903-5_6

    DO - 10.1007/978-1-4614-3903-5_6

    M3 - Chapter

    AN - SCOPUS:84930327421

    SN - 9781461439035

    SN - 1461439027

    SN - 9781461439028

    SP - 109

    EP - 129

    BT - Adenosine: A Key Link between Metabolism and Brain Activity

    PB - Springer

    ER -

    Nedden SZ, Doney AS, Frenguelli BG. The double-edged sword: gaining adenosine at the expense of ATP. How to balance the books. In Adenosine: A Key Link between Metabolism and Brain Activity. Springer . 2013. p. 109-129 https://doi.org/10.1007/978-1-4614-3903-5_6