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GLOSSARY
- Cys=
- cysteine;
- GABA=
- γ-aminobutyric acid;
- GlyR=
- glycine receptor;
- KCC2=
- K+, Cl− cotransporter 2;
- NKH=
- nonketotic hyperglycinemia;
- NMDAR=
- NMDA receptor;
- VGAT=
- vesicular GABA transporter;
- VIAAT=
- vesicular inhibitory amino acid transporter.
Glycine is a major neurotransmitter of inhibitory neurons in the spinal cord and brainstem. In many of these neurons, glycine coexists with γ-aminobutyric acid (GABA). The synaptic availability of glycine is controlled by 2 different transporters, and its postsynaptic effects are mediated by a specific chloride (Cl−) channel receptor. In the adult nervous system, glycine exerts fast postsynaptic inhibition that is important for control of excitability of motor neurons, auditory processing, pain transmission in the dorsal horn, and other functions. Corelease of GABA may affect the temporal profile of the postsynaptic effects of glycine. Glycine is also a coagonist of glutamate on NMDA receptors (NMDARs). Studies in vitro and in knockout mouse models have provided insight on the complex synaptic interactions among glycine, GABA, and glutamate, and on the consequences of impaired regulation of glycinergic transmission in the nervous system. Excessive synaptic levels of glycine may explain the manifestations of nonketotic hyperglycinemia, whereas loss-of-function mutations impairing glycinergic signaling have been linked to familial hyperekplexia. Autoimmune disorders affecting the glycine receptor (GlyR) complex may also result in excessive motoneuron excitability. Pharmacologic blockade of a glycine transporter may constitute a novel approach to increase NMDAR activity in schizophrenia. Many of these topics have been recently reviewed.1,–,9
GLYCINE AS A NEUROTRANSMITTER: VESICULAR STORAGE AND TRANSPORT MECHANISM
Synthesis and storage.
Glycine is the primary neurotransmitter of many inhibitory interneurons in the spinal cord and brainstem, including the ventral horn and motor cranial nerve nuclei, dorsal horn and trigeminal nuclei, and auditory and vestibular systems; it also mediates inhibitory effects of some amacrine cells and Golgi cells of the cerebellum.1 Glycine also has an essential role in intermediate metabolism; for example, it is the precursor to the one-carbon pool of folic acid intermediates that are fundamental to many synthetic reactions. Glycine is catabolized via the glycine cleavage system, a group …
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