By Arne Schousboe, Ursula Sonnewald
Fundamental biochemical stories of easy mind metabolism concentrating on the neuroactive amino acids glutamate and GABA mixed with the seminal remark that one of many key enzymes, glutamine synthetase is localized in astroglial cells yet now not in neurons led to the formula of the time period “The Glutamate-Glutamine Cycle.” during this cycle glutamate published from neurons is taken up by means of surrounding astrocytes, amidated by means of the motion of glutamine synthetase to glutamine that are transferred again to the neurons. The conversion of glutamate to glutamine is sort of a stealth expertise, hiding the glutamate molecule which might be hugely poisonous to neurons because of its excitotoxic motion. This sequence of reactions require the concerted and exact interplay of a couple of enzymes and plasma membrane transporters, and this quantity offers in-depth descriptions of those approaches. evidently this kind of sequence of advanced reactions could be liable to malfunction and for this reason neurological illnesses usually are linked to such malfunction of the enzymes and transporters fascinated with the cycle. those facets also are mentioned in different chapters of the book.
A variety of best specialists in neuroscience together with middleman metabolism, enzymology and transporter body structure have contributed to this publication which gives finished discussions of those varied facets of the sensible significance of the glutamate-glutamine cycle coupling homeostasis of glutamatergic, excitatory neurotransmission to uncomplicated features of mind power metabolism. This booklet can be of specific value for college kids in addition to pros drawn to those primary methods eager about mind functionality and dysfunction.
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Extra resources for The Glutamate/GABA-Glutamine Cycle: Amino Acid Neurotransmitter Homeostasis
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Neurobiol Dis 25(2):319–330 Bjørnsen LP, Hadera MG, Zhou Y, Danbolt NC, Sonnewald U (2014) The GLT-1 (EAAT2; slc1a2) glutamate transporter is essential for glutamate homeostasis in the neocortex of the mouse. J Neurochem 128(5):641–649 Boumezbeur F, Petersen KF, Cline GW, Mason GF, Behar KL, Shulman GI, Rothman DL (2010) The contribution of blood lactate to brain energy metabolism in humans measured by dynamic 13 C nuclear magnetic resonance spectroscopy. J Neurosci 30(42):13983–13991 Bouzier-Sore AK, Voisin P, Canioni P, Magistretti PJ, Pellerin L (2003) Lactate is a preferential oxidative energy substrate over glucose for neurons in culture.
Neurochem Res 37(11):2439–2455 Cooper AJ (2013) Quantitative analysis of neurotransmitter pathways under steady state conditions—a perspective. Front Endocrinol (Lausanne) 4:179 (Hertz L, Rodrigues TB (Eds). eCollection) Cremer JE, Braun LD, Oldendorf WH (1976) Changes during development in transport processes of the blood-brain barrier. Biochim Biophys Acta 448(4):633–637 Cruz NF, Ball KK, Dienel GA (2007) Functional imaging of focal brain activation in conscious rats: impact of [(14)C]glucose metabolite spreading and release.
Accordingly, the glutamine accumulated into the mitochondria does not give rise to any formation of GABA, but it is essential for the transamination of incoming GABA to SSA, and it also delivers aspartate for the subsequent conversion of succinate-derived alpha-KG to glutamate and glutamate for return to astrocytes. CoA to alpha-KG which is transaminated to glutamate, and conversion of aspartate to OAA. This glutamate molecule exits to the cytosol (in exchange with GABA) and is again decarboxylated to a molecule of GABA which is released as synaptic GABA (arrow 3).