Metabolic flux analysis as a tool for the elucidation of the metabolism of neurotransmitter glutamate.

A flux analysis model for the metabolism of neurotransmitter glutamate is constructed, in order to study functional aspects of its metabolism. This work is based on the potassium [K(+)] evoked neurotransmitter glutamate released, as measured in a series of experiments of superfused rat or mouse brain preparations. These measurements are combined with data reported, concerning the metabolism of glutamate and its precursors, glutamine and glucose in rat cerebral cells in vivo. The proposed stoichiometry of the specific reaction network renders the model solvable. The classification procedure establishes that the measured fluxes are all balanceable and all non-measured fluxes can be calculated. The system is well posed with a condition number of 7.8536. The results emphasize the importance of phosphate activated glutaminase and aspartate aminotransferase in the metabolism of neurotransmitter glutamate. Reported data on the rate of the malate-aspartate shuttle, as well as the anaplerotic flux of the glial pyruvate carboxylase reaction are in agreement with the estimations calculated from the proposed model.