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Anaplerosis for Glutamate Synthesis in the Neonate and in Adulthood

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The Glutamate/GABA-Glutamine Cycle

Part of the book series: Advances in Neurobiology ((NEUROBIOL,volume 13))

Abstract

A central task of the tricarboxylic acid (TCA, Krebs, citric acid) cycle in brain is to provide precursors for biosynthesis of glutamate, GABA, aspartate and glutamine. Three of these amino acids are the partners in the intricate interaction between astrocytes and neurons and form the so-called glutamine–glutamate (GABA) cycle. The ketoacids α-ketoglutarate and oxaloacetate are removed from the cycle for this process. When something is removed from the TCA cycle it must be replaced to permit the continued function of this essential pathway, a process termed anaplerosis. This anaplerotic process in the brain is mainly carried out by pyruvate carboxylation performed by pyruvate carboxylase. The present book chapter gives an introduction and overview into this carboxylation and additionally anaplerosis mediated by propionyl-CoA carboxylase under physiological conditions in the adult and in the developing rodent brain. Furthermore, examples are given about pathological conditions in which anaplerosis is disturbed.

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Abbreviations

AD:

Alzheimer’s disease

AMPA:

α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

AMPK:

AMP activated protein kinase

CBZ:

Carbamazepine

GS:

Glutamine synthetase

ME:

Malic enzyme

MRS:

Magnetic resonance spectroscopy

P:

Postnatal day

PAG:

Phosphate activated glutaminase

PC:

Pyruvate carboxylase

PCC:

Propionyl-CoA carboxylase

PDH:

Pyruvate dehydrogenase

PEPCK:

Phosphoenolpyruvate carboxykinase

PPP:

Pentose phosphate pathway

PTZ:

Pentylenetetrazole

TCA:

Tricarboxylic acid

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Authors and Affiliations

  1. Department of Pediatrics, Nordland Hospital Trust, Bodo, Norway

    Eva Brekke

  2. Department of Ophthalmology, Trondheim University Hospital, Trondheim, 7006, Norway

    Tora Sund Morken

  3. Department of Laboratory Medicine, Children’s and Women’s Health, Norwegian University of Science and Technology (NTNU), Trondheim, 7489, Norway

    Tora Sund Morken

  4. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, 2100, Denmark

    Anne B. Walls, Helle Waagepetersen, Arne Schousboe & Ursula Sonnewald

  5. Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Postboks 8905, Trondheim, 7489, Norway

    Ursula Sonnewald

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  1. Eva Brekke
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Correspondence to Ursula Sonnewald .

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Editors and Affiliations

  1. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Arne Schousboe

  2. Department of Neuroscience, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

    Ursula Sonnewald

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Brekke, E., Morken, T.S., Walls, A.B., Waagepetersen, H., Schousboe, A., Sonnewald, U. (2016). Anaplerosis for Glutamate Synthesis in the Neonate and in Adulthood. In: Schousboe, A., Sonnewald, U. (eds) The Glutamate/GABA-Glutamine Cycle. Advances in Neurobiology, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-319-45096-4_3

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