Chapter 1 Biochemistry and anatomy of transmitter glutamate

summary The reviewed literature leaves us with an impression of the cellular interchange of Glu and its precursors and metabolites (Fig.. 2) that is somewhat different from the classical idea of the ‘glutamine“ cycle with its near-stoichiometric exchange of Glu and glutamine between neurons and astrocytes. (1) Glu is synthesized from glutamine, as previously thought, but also from neuronal precursors supplied by neuronal pyruvate carboxylation. (2) Transmitter Glu is mostly taken up into astrocytes for conversion to glutamine, but an unknown fraction is metabolized by the astrocytic TCA cycle, either fully to CO 2 and water, or only partially, to malate which is converted to pyruvate and hence lactate. (3) Uptake of Glu into astrocytes stimulates astrocytic uptake of serum glucose and export of lactate to the extracellular fluid. (4) Lactate, whether formed from transmitter Glu or serum glucose, may increase regional cerebral blood flow and act as a main neuronal energy substrate. (5) Glutamine is shunted to neurons where it to a large extent is metabolized to CO 2 and water and, possibly to a lesser extent, is converted to transmitter Glu. (6) The uptake processes related to the handling of transmitter Glu and glutamine together with the formation of glutamine cause the expenditure of % of the total energy of the serum glucose taken up by the brain.