KEGG PATHWAY: ko04724

PATHWAY: ko04724

Entry

ko04724 Pathway

Name

Glutamatergic synapse

Description

Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system(CNS). Glutamate is packaged into synaptic vesicles in the presynaptic terminal. Once released into the synaptic cleft, glutamate acts on postsynaptic ionotropic glutamate receptors (iGluRs) to mediate fast excitatory synaptic transmission. Glutamate can also act on metabotropic glutamate receptors (mGluRs) and exert a variety of modulatory effects through their coupling to G proteins and the subsequent recruitment of second messenger systems. Presynaptically localized Group II and Group III mGluRs are thought to represent the classical inhibitory autoreceptor mechanism that suppresses excess glutamate release. After its action on these receptors, glutamate can be removed from the synaptic cleft by EAATs located either on the presynaptic terminal, neighboring glial cells, or the postsynaptic neuron. In glia, glutamate is converted to glutamine, which is then transported back to the presynaptic terminal and converted back to glutamate.

Class

Organismal Systems; Nervous system

Pathway map

ko04724

Glutamatergic synapse

Disease

H00577	Syndromic X-linked mental retardation with epilepsy or seizures
H00749	Episodic ataxias
H00768	Nonsyndromic autosomal recessive mental retardation (NS-ARMR)
H00775	Familial or sporadic hemiplegic migraine
H00787	Congenital stationary night blindness (CSNB)
H00911	Dicarboxylic aminoaciduria
H00923	Congenital systemic glutamine deficiency (CSGD)
H01238	Phelan-McDermid syndrome

Other DBs

BSID:

213811

GO:

0051966

Orthology

K14990	solute carrier family 38 (sodium-coupled neutral amino acid transporter), member 1
K14207	solute carrier family 38 (sodium-coupled neutral amino acid transporter), member 2
K01425	glutaminase [EC:3.5.1.2]
K12302	MFS transporter, ACS family, solute carrier family 17 (sodium-dependent inorganic phosphate cotransporter), member 6/7/8
K05201	glutamate receptor, ionotropic kainate 1
K05202	glutamate receptor, ionotropic kainate 2
K05203	glutamate receptor, ionotropic kainate 3
K05204	glutamate receptor, ionotropic kainate 4
K05205	glutamate receptor, ionotropic kainate 5
K05197	glutamate receptor 1
K05198	glutamate receptor 2
K05199	glutamate receptor 3
K05200	glutamate receptor 4
K05208	glutamate receptor ionotropic, NMDA 1
K05209	glutamate receptor ionotropic, NMDA 2A
K05210	glutamate receptor ionotropic, NMDA 2B
K05211	glutamate receptor ionotropic, NMDA 2C
K05212	glutamate receptor ionotropic, NMDA 2D
K05213	glutamate receptor ionotropic, NMDA 3A
K05214	glutamate receptor ionotropic, NMDA 3B
K04348	protein phosphatase 3, catalytic subunit [EC:3.1.3.16]
K06268	protein phosphatase 3, regulatory subunit
K11828	discs large protein 4
K15008	discs, large-associated protein 1
K15009	SH3 and multiple ankyrin repeat domains protein
K04964	transient receptor potential cation channel subfamily C member 1
K04603	metabotropic glutamate receptor 1
K04604	metabotropic glutamate receptor 5
K15010	homer
K04634	guanine nucleotide-binding protein G(q) subunit alpha
K05858	phosphatidylinositol phospholipase C, beta [EC:3.1.4.11]
K02677	classical protein kinase C [EC:2.7.11.13]
K04958	inositol 1,4,5-triphosphate receptor type 1
K04959	inositol 1,4,5-triphosphate receptor type 2
K04960	inositol 1,4,5-triphosphate receptor type 3
K16342	cytosolic phospholipase A2 [EC:3.1.1.4]
K01115	phospholipase D1/2 [EC:3.1.4.4]
K04371	extracellular signal-regulated kinase 1/2 [EC:2.7.11.24]
K04632	guanine nucleotide-binding protein G(s) subunit alpha
K08041	adenylate cyclase 1 [EC:4.6.1.1]
K08042	adenylate cyclase 2 [EC:4.6.1.1]
K08043	adenylate cyclase 3 [EC:4.6.1.1]
K08044	adenylate cyclase 4 [EC:4.6.1.1]
K08045	adenylate cyclase 5 [EC:4.6.1.1]
K08046	adenylate cyclase 6 [EC:4.6.1.1]
K08047	adenylate cyclase 7 [EC:4.6.1.1]
K08048	adenylate cyclase 8 [EC:4.6.1.1]
K08049	adenylate cyclase 9 [EC:4.6.1.1]
K04345	protein kinase A [EC:2.7.11.11]
K04605	metabotropic glutamate receptor 2/3
K04607	metabotropic glutamate receptor 4
K04608	metabotropic glutamate receptor 6/7/8
K04630	guanine nucleotide-binding protein G(i) subunit alpha
K04534	guanine nucleotide-binding protein G(o) subunit alpha
K04536	guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1
K04537	guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-2
K07825	guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3
K04538	guanine nucleotide-binding protein subunit beta-4
K04539	guanine nucleotide-binding protein subunit beta-5
K07826	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2
K04540	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-3
K04541	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-4
K04542	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-5
K04543	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-7
K04544	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-8
K04545	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-10
K04546	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-11
K04347	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12
K04547	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-13
K04548	guanine nucleotide-binding protein G(T) subunit gamma-T1
K04549	guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-T2
K00910	beta-adrenergic-receptor kinase [EC:2.7.11.15]
K04997	potassium inwardly-rectifying channel subfamily J member 3
K04344	voltage-dependent calcium channel P/Q type alpha-1A
K05613	solute carrier family 1 (glial high affinity glutamate transporter), member 2
K05618	solute carrier family 1 (glutamate transporter), member 7
K05612	solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter), member 1
K05617	solute carrier family 1 (high affinity aspartate/glutamate transporter), member 6
K04850	voltage-dependent calcium channel L type alpha-1C
K04851	voltage-dependent calcium channel L type alpha-1D
K05614	solute carrier family 1 (glial high affinity glutamate transporter), member 3
K01915	glutamine synthetase [EC:6.3.1.2]
K13576	solute carrier family 38 (sodium-coupled neutral amino acid transporter), member 3

Compound

C00025	L-Glutamate
C00064	L-Glutamine
C00076	Calcium cation
C00165	Diacylglycerol
C00238	Potassium cation
C00575	3',5'-Cyclic AMP
C01245	D-myo-Inositol 1,4,5-trisphosphate
C01330	Sodium cation

Reference

PMID:20055706

Authors

Niswender CM, Conn PJ

Title

Metabotropic glutamate receptors: physiology, pharmacology, and disease.

Journal

Annu Rev Pharmacol Toxicol 50:295-322 (2010)

Reference

PMID:19112153

Authors

Ferraguti F, Crepaldi L, Nicoletti F

Title

Metabotropic glutamate 1 receptor: current concepts and perspectives.

Journal

Pharmacol Rev 60:536-81 (2008)

Reference

PMID:11672421

Authors

Hermans E, Challiss RA

Title

Structural, signalling and regulatory properties of the group I metabotropic glutamate receptors: prototypic family C G-protein-coupled receptors.

Journal

Biochem J 359:465-84 (2001)

Reference

PMID:17663464

Authors

Kim CH, Lee J, Lee JY, Roche KW

Title

Metabotropic glutamate receptors: phosphorylation and receptor signaling.

Journal

J Neurosci Res 86:1-10 (2008)

Reference

PMID:14684436

Authors

Meador-Woodruff JH, Clinton SM, Beneyto M, McCullumsmith RE

Title

Molecular abnormalities of the glutamate synapse in the thalamus in schizophrenia.

Journal

Ann N Y Acad Sci 1003:75-93 (2003)

Reference

PMID:18425072

Authors

Sanacora G, Zarate CA, Krystal JH, Manji HK

Title

Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders.

Journal

Nat Rev Drug Discov 7:426-37 (2008)

Reference

PMID:17706608

Authors

Gass JT, Olive MF

Title

Glutamatergic substrates of drug addiction and alcoholism.

Journal

Biochem Pharmacol 75:218-65 (2008)

Reference

PMID:9665875

Authors

Palmada M, Centelles JJ

Title

Excitatory amino acid neurotransmission. Pathways for metabolism, storage and reuptake of glutamate in brain.

Journal

Front Biosci 3:d701-18 (1998)

Reference

PMID:11561058

Authors

Schoepp DD

Title

Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system.

Journal

J Pharmacol Exp Ther 299:12-20 (2001)

Reference

PMID:19559598

Authors

de Jong AP, Verhage M

Title

Presynaptic signal transduction pathways that modulate synaptic transmission.

Journal

Curr Opin Neurobiol 19:245-53 (2009)

Reference

PMID:18464791

Authors

Pinheiro PS, Mulle C

Title

Presynaptic glutamate receptors: physiological functions and mechanisms of action.

Journal

Nat Rev Neurosci 9:423-36 (2008)

Reference

PMID:19110202

Authors

Byrnes KR, Loane DJ, Faden AI

Title

Metabotropic glutamate receptors as targets for multipotential treatment of neurological disorders.

Journal

Neurotherapeutics 6:94-107 (2009)

Reference

PMID:10481192

Authors

Conti F, Weinberg RJ

Title

Shaping excitation at glutamatergic synapses.

Journal

Trends Neurosci 22:451-8 (1999)

Reference

PMID:12399578

Authors

Sheng M, Kim MJ

Title

Postsynaptic signaling and plasticity mechanisms.

Journal

Science 298:776-80 (2002)

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Ontology (2)   
   KEGG BRITE (1)   
   GO (1)   
Pathway (2)   
   KEGG PATHWAY (1)   
   BioSystems (1)   
Disease (8)   
   KEGG DISEASE (8)   
Chemical substance (8)   
   KEGG COMPOUND (8)   
Chemical reaction (11)   
   KEGG ENZYME (11)   
Gene (83)   
   KEGG ORTHOLOGY (83)   
Literature (14)   
   PubMed (14)   
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