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Glutaminases

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The Glutamate/GABA-Glutamine Cycle

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

Abstract

Mammalian glutaminases catalyze the stoichiometric conversion of l-glutamine to l-glutamate and ammonium ions. In brain, glutaminase is considered the prevailing pathway for synthesis of the neurotransmitter pool of glutamate. Besides neurotransmission, the products of glutaminase reaction also fulfill crucial roles in energy and metabolic homeostasis in mammalian brain. In the last years, new functional roles for brain glutaminases are being uncovered by using functional genomic and proteomic approaches. Glutaminases may act as multifunctional proteins able to perform different tasks: the discovery of multiple transcript variants in neurons and glial cells, novel extramitochondrial localizations, and isoform-specific proteininteracting partners strongly support possible moonlighting functions for these proteins. In this chapter, we present a critical account of essential works on brain glutaminase 80 years after its discovery. We will highlight the impact of recent findings and thoughts in the context of the glutamate/glutamine brain homeostasis.

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Abbreviations

AGC:

Aspartate–glutamate carrier

BBB:

Blood-brain barrier

EM:

Electron microscopy

GA:

Phosphate-activated glutaminase

GAB:

Gls2-encoded long GA isoform

GAC:

Gls-encoded short GA isoform

GAD:

Glutamic acid decarboxylase

GDH:

Glutamate dehydrogenase

GFAP:

Glial fibrillary acidic protein

GIP:

Glutaminase-interacting protein

GS:

Glutamine synthetase

IMM:

Inner mitochondrial membrane

KGA:

Gls-encoded long GA isoform

LGA:

Gls2-encoded short GA isoform

NBT:

Nitroblue tetrazolium

NMR:

Nuclear magnetic resonance

NPCs:

Neural progenitor cells

PDZ:

PSD95/Dlg/ZO1 domains

TCA:

Tricarboxylic acid cycle

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Acknowledgements

We are grateful to everybody in the Canceromics group for creating most of the own work described in this chapter, particularly to our colleagues F.J. Alonso, J.A. Segura, M. Martín-Rufián, C. Cardona, C. Lobo, A. Peñalver, and former members L. Olalla, P. Gómez-Fabre, C. Pérez-Gómez, and J.C. Aledo. The excellent collaboration of Dr. Antonia Gutiérrez and her team is also gratefully acknowledged. We are in debt with Dr. Alfonso Gutiérrez-Adán, Dr. Fernando Rodríguez de Fonseca, and Dr. Emilio Ambrosio for helpful discussions and collaborations with animal models. This work was supported by Excellence Grant CVI-6656 (Regional Andalusian government) and Grant RD12/0028/0013 of the RTA RETICS network from the Spanish Health Institute Carlos III. Thanks are due to Mrs. Kristina Pačesaitė for the design of the graphic work and to Mrs. Laura Castilla for excellent technical work.

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  1. Departamento de Biología Molecular y Bioquímica, Canceromics Lab, Facultad de Ciencias, Universidad de Málaga, Málaga, 29071, Spain

    Javier Márquez, José M. Matés & José A. Campos-Sandoval

  2. Instituto de Investigación Biomédica de Málaga (IBIMA), Málaga, Spain

    Javier Márquez, José M. Matés & José A. Campos-Sandoval

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  1. Javier Márquez
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  2. José M. Matés
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Correspondence to Javier Márquez .

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  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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Márquez, J., Matés, J.M., Campos-Sandoval, J.A. (2016). Glutaminases. 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_6

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