Mitochondrial/cytosolic interactions via metabolite shuttles and transporters

Abstract

This chapter concerns the metabolism of glutamate, aspartate, and γ-aminobutyric acid (GABA) in the central nervous system. There appears to be a striking interplay between the metabolism of these neurotransmitters and the levels available for neurotransmission. The interplay is mediated by various inter- and intracellular metabolic cyclic shuttle systems that actively transport the transmitters into astrocytes after their release to the synaptic space and then catalyze the return of derivatives of these compounds to the neurons for transmitter regeneration. The intercellular shuttle systems considered are the glutamate/glutamine cycle, the aspartate/glutamine cycle, the GABA/glutamine cycle, and the astrocyte/neuron lactate shuttle. Shuttle systems that operate intracellularly, within astrocytes, are also considered. These intracellular shuttles include one that converts glutamate to lactate and then via a different pathway, lactate back to glutamate. Lastly, we consider the well-known malate/aspartate cycle that acts within cells to transport reducing equivalents generated in the cytosol from the cytosol to the mitochondria. We postulate that differences in the activity of this cycle in different cell types influence metabolic traffic flow. The specific expression of the cycle within the brain, the physiological advantages of spatial specificity, and the molecular basis for the specificity are considered and discussed. © 2007 Springer Science+Business Media, LLC.