Glycine is a nonessential amino acid that also functions as a neurotransmitter in the CNS. Although the exact metabolic pathway for glycine production has yet to be fully elucidated, evidence suggests that glycine may be produced in the CNS by two distinct pathways. First, glycine is produced from serine by the enzyme serine-trans-hydroxymethylase in a reversible folate-dependent reaction (Cooper et al. 2001; Squire et al. 2003). Additionally, glycine may be produced from glyoxylate by the enzyme D-glycerate dehydrogenase. This amino acid is found in higher concentrations in the spinal cord than in the rest of the CNS. Glycine acts as an inhibitory neurotransmitter predominantly in the brain stem and spinal cord (Nestler et al. 2001). As discussed earlier, a very important role that glycine also plays is to augment the NMDA-mediated frequency of NMDA receptor channel opening. This effect is strychnine-insensitive and pharmacologically suggests that the actions of glycine on NMDA receptor function are different from its effect on the spinal cord, where glycine's inhibitory effect is blocked by strychnine (Cooper et al. 2001). The allosteric modulation of NMDA receptors via a glycine-insensitive site is further underscored by receptor binding experiments yielding an anatomic distribution similar to that of NMDA receptors. Functionally, it has been postulated that glycine is able to augment the NMDA-mediated responses by speeding up the recovery process of the receptor (Cooper et al. 2001). Given the ability of glycine to alter NMDA function, glycine may be beneficial in the treatment of schizophrenia (Coyle et al. 2002).

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