The undertow of sulfur metabolism on glutamatergic neurotransmission

Metabolic interdependence between specialized cells in an organ represents a strategy for energy economy by requiring expression of only a subset of pathway genes in a given cell type. In brain, sulfur metabolism exemplifies this principle of metabolic cooperation between glial and neuronal cells and furnishes three key reagents: S-adenosylmethionine, glutathione and taurine. The pathways for glutathione and taurine syntheses depend on metabolic integration between astrocytes and neurons and intersect with the glutamine-glutamate cycle, which underlies glutamatergic synaptic transmission and requires cooperation between these cell types. We propose that underlying waves of glutamate clearance by astrocytes are activation of cystine import and taurine efflux that result, respectively, from a shared transporter and an increase in solute concentration that triggers osmoregulatory responses.