Neurotransmitter uptake and metabolism In glial cells (Homo sapiens)

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Bibliography

1. Häberle J, Görg B, Rutsch F, Schmidt E, Toutain A, Benoist JF, Gelot A, Suc AL, Höhne W, Schliess F, Häussinger D, Koch HG.; ''Congenital glutamine deficiency with glutamine synthetase mutations.''; PubMed Europe PMC Scholia
2. Gegelashvili M, Rodriguez-Kern A, Pirozhkova I, Zhang J, Sung L, Gegelashvili G.; ''High-affinity glutamate transporter GLAST/EAAT1 regulates cell surface expression of glutamine/neutral amino acid transporter ASCT2 in human fetal astrocytes.''; PubMed Europe PMC Scholia
3. Maragakis NJ, Dietrich J, Wong V, Xue H, Mayer-Proschel M, Rao MS, Rothstein JD.; ''Glutamate transporter expression and function in human glial progenitors.''; PubMed Europe PMC Scholia
4. Krajewski WW, Collins R, Holmberg-Schiavone L, Jones TA, Karlberg T, Mowbray SL.; ''Crystal structures of mammalian glutamine synthetases illustrate substrate-induced conformational changes and provide opportunities for drug and herbicide design.''; PubMed Europe PMC Scholia

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DataNodes

Name	Type	Database reference	Comment
ADP	Metabolite	CHEBI:16761 (ChEBI)
ATP	Metabolite	CHEBI:15422 (ChEBI)
Astrocytic EAATs		REACT_14651 (Reactome)
GLUL [cytosol]	Protein	P15104 (Uniprot-TrEMBL)
GLUL decamer	Complex	REACT_3307 (Reactome)
Glu	Metabolite	CHEBI:16015 (ChEBI)
L-Gln	Metabolite	CHEBI:18050 (ChEBI)
L-Glu	Metabolite	CHEBI:16015 (ChEBI)
NH4+	Metabolite	CHEBI:28938 (ChEBI)
Pi	Metabolite	CHEBI:18367 (ChEBI)
SLC38A1	Protein	Q9H2H9 (Uniprot-TrEMBL)

Annotated Interactions

Source	Target	Type	Database reference	Comment
	ADP	Arrow	REACT_1171 (Reactome)
ATP			REACT_1171 (Reactome)
Astrocytic EAATs		mim-catalysis	REACT_13588 (Reactome)
GLUL decamer		mim-catalysis	REACT_1171 (Reactome)
Glu			REACT_13588 (Reactome)
	L-Gln	Arrow	REACT_1171 (Reactome)
	L-Gln	Arrow	REACT_13773 (Reactome)
L-Gln			REACT_13773 (Reactome)
	L-Glu	Arrow	REACT_13588 (Reactome)
L-Glu			REACT_1171 (Reactome)
NH4+			REACT_1171 (Reactome)
	Pi	Arrow	REACT_1171 (Reactome)
			REACT_1171 (Reactome)	Cytosolic glutamine synthetase (glutamate-ammonia ligase - GLUL) catalyzes the reaction of glutamate, ammonia, and ATP to form glutamine, ADP, and orthophosphate. The enzyme is a decamer (Krajewski et al. 2008). Mutations in the gene encoding GLUL cause glutamine deficiency in vivo (Haberle et al. 2005).
			REACT_13588 (Reactome)	Excess L-Glutamate released by the pre-synaptic neuron in the synaptic cleft is cleared by high affinity transporters called the excitatory amino acid transporters (EAATs) to terminate synaptic actions of the neurotransmitter and to recycle these molecules. Five types of EAATs have been identified EAAT1-EAAT5 in the mammalian CNS. EAAT1 and EAAT2 are mainly expressed by astrocytes whereas EAAT3 and EAAT4 are predominantly neuronal. EAAT3 are expressed throughout the CNS however, EAAT4 is predominantly localized to purkinje cells. EAAT5 are expressed rod photoreceptor and bipolar cells of retina. Astrocytic EAATs are expressed in astrocytes in close apposition to the synapses and neuronal EAATs are expressed in the extra-synaptic or peri-synaptic locations on the neurons. Astrocytic EAATs are responsible for majority of the glutamate uptake, neuronal transporters are responsible for glutamate clearance in specialized synapses in cerebellum where the spatial relationship between the glutamate receptors and EAATs is altered and glutamate receptors are expressed in the peri-synaptic region.
			REACT_13773 (Reactome)	Glutamine from the astrocytes is exported to the extracellular compartment via the system N amino acid transporter. The system N transporter is Na+ dependant transporter that has substrate specificity to aspargine, glutamine and histidine.
SLC38A1		mim-catalysis	REACT_13773 (Reactome)