Neurochemical Research

, Volume 37, Issue 11, pp 2554–2561 | Cite as

Metabolic Pathways and Activity-Dependent Modulation of Glutamate Concentration in the Human Brain

  • Silvia MangiaEmail author
  • Federico Giove
  • Mauro DiNuzzo


Glutamate is one of the most versatile molecules present in the human brain, involved in protein synthesis, energy production, ammonia detoxification, and transport of reducing equivalents. Aside from these critical metabolic roles, glutamate plays a major part in brain function, being not only the most abundant excitatory neurotransmitter, but also the precursor for γ-aminobutyric acid, the predominant inhibitory neurotransmitter. Regulation of glutamate levels is pivotal for normal brain function, as abnormal extracellular concentration of glutamate can lead to impaired neurotransmission, neurodegeneration and even neuronal death. Understanding how the neuron-astrocyte functional and metabolic interactions modulate glutamate concentration during different activation status and under physiological and pathological conditions is a challenging task, and can only be tentatively estimated from current literature. In this paper, we focus on describing the various metabolic pathways which potentially affect glutamate concentration in the brain, and emphasize which ones are likely to produce the variations in glutamate concentration observed during enhanced neuronal activity in human studies.


Aspartate Glutamate Human brain Homeostasis In vivo studies Malate-aspartate shuttle Neuron-astrocyte interactions Neurotransmission Neuronal stimulation 





Alanine aminotransferase


Aspartate-glutamate carrier


Branched-chain aminotrasferases


Branched-chain keto acid dehydrogenase complex


Cytosolic aspartate amino-transferase


Cytosolic malic enzyme


Citrate synthase


Dicarboxylate carrier


Excitatory amino acids transporter


γ-Aminobutyric acid


Glutamate decarboxylase


Glutamate/hydroxyl carrier


Glutamate-cysteine ligase


Glutamate dehydrogenase


Glutamine synthetase


Mitochondrial aspartate amino-transferase


Malate-aspartate shuttle


Monocarboxylate transporter


Mitochondrial malic enzyme




Phosphate-activated glutaminase


Pyruvate carboxylase




Tricarboxylic acid



S. M. thanks the grant NIH R01 DK62440 for support. This project was also supported by the National Center for Research Resources (Grant Number P41 RR008079) and the National Institute of Biomedical Imaging and Bioengineering (Grant Number P41 EB015894) of NIH. Additional funding supports to CMRR are: Minnesota Medical Foundation, and P30 NS057091. This work was finally supported by the NIH grant 1UL1RR033183 and KL2 RR033182 from the National Center for Research Resources (NCRR) to the University of Minnesota Clinical and Translational Science Institute (CTSI).


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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Silvia Mangia
    • 1
    Email author
  • Federico Giove
    • 2
    • 3
  • Mauro DiNuzzo
    • 2
    • 3
  1. 1.Department of Radiology, Center for Magnetic Resonance ResearchUniversity of MinnesotaMinneapolisUSA
  2. 2.MARBILabMuseo storico della fisica e Centro di studi e ricerche “Enrico Fermi”RomeItaly
  3. 3.Department of PhysicsUniversity of Rome “La Sapienza”RomeItaly

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