Glucose, Lactate, β-Hydroxybutyrate, Acetate, GABA, and Succinate as Substrates for Synthesis of Glutamate and GABA in the Glutamine–Glutamate/GABA Cycle View Full Text


Ontology type: schema:Chapter     


Chapter Info

DATE

2016

AUTHORS

Leif Hertz , Douglas L. Rothman

ABSTRACT

The glutamine-glutamate/GABA cycle is an astrocytic-neuronal pathway transferring precursors for transmitter glutamate and GABA from astrocytes to neurons. In addition, the cycle carries released transmitter back to astrocytes, where a minor fraction (~25 %) is degraded (requiring a similar amount of resynthesis) and the remainder returned to the neurons for reuse. The flux in the cycle is intense, amounting to the same value as neuronal glucose utilization rate or 75-80 % of total cortical glucose consumption. This glucose:glutamate ratio is reduced when high amounts of β-hydroxybutyrate are present, but β-hydroxybutyrate can at most replace 60 % of glucose during awake brain function. The cycle is initiated by α-ketoglutarate production in astrocytes and its conversion via glutamate to glutamine which is released. A crucial reaction in the cycle is metabolism of glutamine after its accumulation in neurons. In glutamatergic neurons all generated glutamate enters the mitochondria and its exit to the cytosol occurs in a process resembling the malate-aspartate shuttle and therefore requiring concomitant pyruvate metabolism. In GABAergic neurons one half enters the mitochondria, whereas the other one half is released directly from the cytosol. A revised concept is proposed for the synthesis and metabolism of vesicular and nonvesicular GABA. It includes the well-established neuronal GABA reuptake, its metabolism, and use for resynthesis of vesicular GABA. In contrast, mitochondrial glutamate is by transamination to α-ketoglutarate and subsequent retransamination to releasable glutamate essential for the transaminations occurring during metabolism of accumulated GABA and subsequent resynthesis of vesicular GABA. More... »

PAGES

9-42

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  • Identifiers

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    http://scigraph.springernature.com/pub.10.1007/978-3-319-45096-4_2

    DOI

    http://dx.doi.org/10.1007/978-3-319-45096-4_2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1079359544

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/27885625


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