Category: biosynthesis
CNS glutamate handling — neuronal release after synaptic firing, astrocyte uptake via EAAT1/EAAT2, conversion to glutamine via glutamine synthetase (avoids excitotoxicity), glutamine shuttle back to neuron, conversion back to glutamate via glutaminase. Also peripheral glutamate involvement in TCA anaplerosis (α-KG ↔ glutamate via glutamate dehydrogenase or aminotransferases). Glutamate is the dominant CNS excitatory transmitter; NMDA + AMPA + kainate ionotropic + 8 mGluR metabotropic. Ketamine + memantine = NMDA antagonists; perampanel = AMPA antagonist; tiagabine GAT-1 transporter is downstream into GABA (the inhibitory mirror). Hepatic encephalopathy = ammonia rises because hepatic glutamine synthetase fails; lactulose + rifaximin shift gut microbiome to reduce NH3 production.