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Decarboxylation of l-glutamate to GABA catalyzed by glutamate decarboxylase

Pyridoxal 5'-phosphate is an essential cofactor for glutamic acid decarboxylase, which catalyzes the decarboxylation of glutamate to gamma-amino butyric acid and carbon dioxide. Because glutamate is an excitatory neurotransmitter, whereas GABA is an inhibitory neurotransmitter, the net effect of interfering with either pyridoxal 5-phosphate or GAD is to shift the balance of neural signaling to a more excitatory state. Because the metabolic product of the mushroom toxin gyromitrin, monomethylhydrazine, binds to and inhibits pyridoxal phosphokinase, can result in CNS excitation and seizures that are refractory to standard anticonvulsant therapy. Monomethylhydrazine may interfere with GABA synthesis by additional mechanisms: (1) inhibiting GAD directly; (2) inhibiting pyridoxine phosphokinase, which converts pyridoxine to its active form (pyridoxal-5'-phosphate). (Source: Yogeswara IBA, Maneerat S, Haltrich D. Glutamate decarboxylase from lactic acid bacteria-a key enzyme in GABA aynthesis. Microorganisms. 2020;8(12):1923. Creative Commons Attribution (CC BY) license.)

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