Quantitative C-13 NMR studies of metabolic compartmentation in the adult mammalian brain

We review the information obtained by C-13 NMR methods on the metabolic com partmentation of the adult mammalian brain with emphasis on its quantitativ e aspects. Classical radiotracer evidence and more recent C-13 NMR results support the presence in the brain of at least two glutamate pools, small an d large, associated with two kinetically different tricarboxylic acid cycle s localized in glia and neurons, respectively. Neuronal and glial cycles in teract closely, utilizing common substrates like glucose and oxygen and exc hanging a variety of metabolites including glutamate, glutamine and GABA. A model for the cerebral metabolism of (1,2-C-13(2)) acetate has made it pos sible to calculate fluxes through both cycles and evaluate the exchanges of glutamate, glutamine and GABA under different physiopathological condition s. Calculated flux values through the neuronal and glial tricarboxylic acid cycles are 1.0 and 0.4 mu mol/min g, respectively. In the adult normoxic b rain, the small and large glutamate pools account for approximately 10% and 90% of cerebral glutamate with estimated turnover times of 1.25 and 5.8/mi n, respectively. Net transfers of neuronal glutamate and GABA to: the glial compartment are calculated to be 0.1 and 0.04 mu mol/min g while transfer of glial glutamine to the neuronal compartment is estimated as 0.1 mu mol/m in g. Pyruvate recycling in the adult brain occurs mainly in the synaptic t erminals with a calculated flux of 0.3 mu mol/min g. These flux values are altered severely in pathological states such as hypothyroidism or ischemia. Copyright (C) 1999 John Wiley & Sons, Ltd.