Cerebral glucose metabolism and the glutamine cycle as detected by in vivo and in vitro 13C NMR spectroscopy.
We review briefly 13C NMR studies of cerebral glucose metabolism with an emphasis on the roles of glial energetics and the glutamine cycle. Mathematical modeling analysis of in vivo 13C turnover experiments from the C4 carbons of glutamate and glutamine are consistent with: (i) the glutamine cycle being the major cerebral metabolic route supporting glutamatergic neurotransmission, (ii) glial glutamine synthesis being stoichiometrically coupled to glycolytic ATP production, (iii) glutamine serving as the main precursor of neurotransmitter glutamate and (iv) glutamatergic neurotransmission being supported by lactate oxidation in the neurons in a process accounting for 60-80% of the energy derived from glucose catabolism. However, more recent experimental approaches using inhibitors of the glial tricarboxylic acid (TCA) cycle (trifluoroacetic acid, TFA) or of glutamine synthase (methionine sulfoximine, MSO) reveal that a considerable portion of the energy required to support glutamine synthesis is derived from the oxidative metabolism of glucose in the astroglia and that a significant amount of the neurotransmitter glutamate is produced from neuronal glucose or lactate rather than from glial glutamine. Moreover, a redox switch has been proposed that allows the neurons to use either glucose or lactate as substrates for oxidation, depending on the relative availability of these fuels under resting or activation conditions, respectively. Together, these results suggest that the coupling mechanisms between neuronal and glial metabolism are more complex than initially envisioned.
García-Espinosa
María A
MA
Laboratorio de Imagen y Espectroscopía por Resonancia Magnética (LIERM), Instituto de Investigaciones Biomédicas Alberto Sols CSIC/UAM, c/ Arturo Duperier 4, E-28029 Madrid, Spain.
Rodrigues
Tiago B
TB
Sierra
Alejandra
A
Benito
Marina
M
Fonseca
Carla
C
Gray
Heather L
HL
Bartnik
Brenda L
BL
García-Martín
María L
ML
Ballesteros
Paloma
P
Cerdán
Sebastián
S
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002247:Carbon Isotopes; D005947:Glucose / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy / Q000379:methods
D002247:Carbon Isotopes; D005973:Glutamine; D000255:Adenosine Triphosphate; D005947:Glucose