KEGG   PATHWAY: hsa04724Help
Entry
hsa04724                    Pathway                                

Name
Glutamatergic synapse - Homo sapiens (human)
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
BRITE hierarchy
Pathway map
Glutamatergic synapse
hsa04724

All organismsOrtholog table
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
Drug
D00537  
Topiramate (JAN/USAN/INN)
D00711  
Ketamine hydrochloride (JP16/USP)
D00777  
Amantadine hydrochloride (JP16/USP)
D00848  
Dextromethorphan hydrobromide hydrate (JP16)
D01445  
Ifenprodil tartrate (JP16)
D02102  
Methadone hydrochloride (JAN/USP)
D02410  
Selfotel (USAN/INN)
D02546  
Kainic acid hydrate (JP16)
D02696  
Talampanel (INN)
D02780  
Acamprosate calcium (JAN/USAN)
D02973  
Aptiganel hydrochloride (USAN)
D03100  
Besonprodil (USAN)
D03679  
Delucemine hydrochloride (USAN)
D03742  
Dextromethorphan (USP)
D03744  
Dextromethorphan polistirex (USAN)
D03746  
Dextrorphan hydrochloride (USAN)
D03878  
Dizocilpine maleate (USAN)
D03966  
Eglumetad (USAN)
D04131  
Farampator (USAN/INN)
D04155  
Fenobam (USAN)
D04226  
Flupirtine maleate (USAN)
D04308  
Gavestinel (USAN/INN)
D04728  
Licostinel (USAN/INN)
D04905  
Memantine hydrochloride (JAN/USAN)
D05145  
Neramexane mesylate (USAN)
D05447  
Perzinfotel (USAN/INN)
D05453  
Phencyclidine hydrochloride (USAN)
D05714  
Remacemide hydrochloride (USAN)
D06146  
Tiletamine hydrochloride (USP)
D06204  
Traxoprodil mesylate (USAN)
D06656  
Tezampanel (USAN)
D07058  
Acamprosate (INN)
D07283  
Esketamine (INN)
D07441  
Amantadine (INN)
D07978  
Flupirtine (INN)
D07979  
Flupirtine D-gluconate
D08064  
Ifenprodil (INN)
D08098  
Ketamine (INN)
D08100  
Ketobemidone (INN)
D08101  
Ketobemidone hydrochloride
D08121  
Levomethadone (INN)
D08122  
Levomethadone hydrochloride
D08174  
Memantine (INN)
D08195  
Methadone (BAN)
D08596  
Tiletamine (INN)
D08908  
Eglumegad (INN)
D08964  
Perampanel (USAN)
D09008  
Talaglumetad hydrochloride (USAN)
D09035  
Zonampanel (INN/USAN)
D09917  
Latrepirdine (USAN/INN)
D09918  
Latrepirdine dihydrochloride (USAN)
D09931  
Mibampator (USAN/INN)
D09949  
Pomaglumetad methionil (USAN/INN)
Other DBs
BSID: 
GO: 
Organism
Homo sapiens (human) [GN:hsa]
Gene
81539  
SLC38A1; solute carrier family 38, member 1 [KO:K14990]
54407  
SLC38A2; solute carrier family 38, member 2 [KO:K14207]
27165  
GLS2; glutaminase 2 (liver, mitochondrial) [KO:K01425] [EC:3.5.1.2]
2744  
GLS; glutaminase [KO:K01425] [EC:3.5.1.2]
57084  
SLC17A6; solute carrier family 17 (vesicular glutamate transporter), member 6 [KO:K12302]
246213  
SLC17A8; solute carrier family 17 (vesicular glutamate transporter), member 8 [KO:K12302]
57030  
SLC17A7; solute carrier family 17 (vesicular glutamate transporter), member 7 [KO:K12302]
2897  
GRIK1; glutamate receptor, ionotropic, kainate 1 [KO:K05201]
2898  
GRIK2; glutamate receptor, ionotropic, kainate 2 [KO:K05202]
2899  
GRIK3; glutamate receptor, ionotropic, kainate 3 [KO:K05203]
2900  
GRIK4; glutamate receptor, ionotropic, kainate 4 [KO:K05204]
2901  
GRIK5; glutamate receptor, ionotropic, kainate 5 [KO:K05205]
2890  
GRIA1; glutamate receptor, ionotropic, AMPA 1 [KO:K05197]
2891  
GRIA2; glutamate receptor, ionotropic, AMPA 2 [KO:K05198]
2892  
GRIA3; glutamate receptor, ionotropic, AMPA 3 [KO:K05199]
2893  
GRIA4; glutamate receptor, ionotropic, AMPA 4 [KO:K05200]
2902  
GRIN1; glutamate receptor, ionotropic, N-methyl D-aspartate 1 [KO:K05208]
2903  
GRIN2A; glutamate receptor, ionotropic, N-methyl D-aspartate 2A [KO:K05209]
2904  
GRIN2B; glutamate receptor, ionotropic, N-methyl D-aspartate 2B [KO:K05210]
2905  
GRIN2C; glutamate receptor, ionotropic, N-methyl D-aspartate 2C [KO:K05211]
2906  
GRIN2D; glutamate receptor, ionotropic, N-methyl D-aspartate 2D [KO:K05212]
116443  
GRIN3A; glutamate receptor, ionotropic, N-methyl-D-aspartate 3A [KO:K05213]
116444  
GRIN3B; glutamate receptor, ionotropic, N-methyl-D-aspartate 3B [KO:K05214]
5530  
PPP3CA; protein phosphatase 3, catalytic subunit, alpha isozyme [KO:K04348] [EC:3.1.3.16]
5532  
PPP3CB; protein phosphatase 3, catalytic subunit, beta isozyme [KO:K04348] [EC:3.1.3.16]
5533  
PPP3CC; protein phosphatase 3, catalytic subunit, gamma isozyme [KO:K04348] [EC:3.1.3.16]
5534  
PPP3R1; protein phosphatase 3, regulatory subunit B, alpha [KO:K06268]
5535  
PPP3R2; protein phosphatase 3, regulatory subunit B, beta [KO:K06268]
1742  
DLG4; discs, large homolog 4 (Drosophila) [KO:K11828]
9229  
DLGAP1; discs, large (Drosophila) homolog-associated protein 1 [KO:K15008]
85358  
SHANK3; SH3 and multiple ankyrin repeat domains 3 [KO:K15009]
50944  
SHANK1; SH3 and multiple ankyrin repeat domains 1 [KO:K15009]
22941  
SHANK2; SH3 and multiple ankyrin repeat domains 2 [KO:K15009]
7220  
TRPC1; transient receptor potential cation channel, subfamily C, member 1 [KO:K04964]
2911  
GRM1; glutamate receptor, metabotropic 1 [KO:K04603]
2915  
GRM5; glutamate receptor, metabotropic 5 [KO:K04604]
9456  
HOMER1; homer homolog 1 (Drosophila) [KO:K15010]
9455  
HOMER2; homer homolog 2 (Drosophila) [KO:K15010]
9454  
HOMER3; homer homolog 3 (Drosophila) [KO:K15010]
2776  
GNAQ; guanine nucleotide binding protein (G protein), q polypeptide [KO:K04634]
23236  
PLCB1; phospholipase C, beta 1 (phosphoinositide-specific) [KO:K05858] [EC:3.1.4.11]
5330  
PLCB2; phospholipase C, beta 2 [KO:K05858] [EC:3.1.4.11]
5331  
PLCB3; phospholipase C, beta 3 (phosphatidylinositol-specific) [KO:K05858] [EC:3.1.4.11]
5332  
PLCB4; phospholipase C, beta 4 [KO:K05858] [EC:3.1.4.11]
5578  
PRKCA; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
5579  
PRKCB; protein kinase C, beta [KO:K02677] [EC:2.7.11.13]
5582  
PRKCG; protein kinase C, gamma [KO:K02677] [EC:2.7.11.13]
3708  
ITPR1; inositol 1,4,5-trisphosphate receptor, type 1 [KO:K04958]
3709  
ITPR2; inositol 1,4,5-trisphosphate receptor, type 2 [KO:K04959]
3710  
ITPR3; inositol 1,4,5-trisphosphate receptor, type 3 [KO:K04960]
123745  
PLA2G4E; phospholipase A2, group IVE [KO:K16342] [EC:3.1.1.4]
5321  
PLA2G4A; phospholipase A2, group IVA (cytosolic, calcium-dependent) [KO:K16342] [EC:3.1.1.4]
8681  
JMJD7-PLA2G4B; JMJD7-PLA2G4B readthrough [KO:K16342] [EC:3.1.1.4]
PLA2G4B; phospholipase A2, group IVB (cytosolic) [KO:K16342] [EC:3.1.1.4]
8605  
PLA2G4C; phospholipase A2, group IVC (cytosolic, calcium-independent) [KO:K16342] [EC:3.1.1.4]
283748  
PLA2G4D; phospholipase A2, group IVD (cytosolic) [KO:K16342] [EC:3.1.1.4]
255189  
PLA2G4F; phospholipase A2, group IVF [KO:K16342] [EC:3.1.1.4]
5337  
PLD1; phospholipase D1, phosphatidylcholine-specific [KO:K01115] [EC:3.1.4.4]
5338  
PLD2; phospholipase D2 [KO:K01115] [EC:3.1.4.4]
5594  
MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
5595  
MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
2778  
GNAS; GNAS complex locus [KO:K04632]
107  
ADCY1; adenylate cyclase 1 (brain) [KO:K08041] [EC:4.6.1.1]
108  
ADCY2; adenylate cyclase 2 (brain) [KO:K08042] [EC:4.6.1.1]
109  
ADCY3; adenylate cyclase 3 [KO:K08043] [EC:4.6.1.1]
196883  
ADCY4; adenylate cyclase 4 [KO:K08044] [EC:4.6.1.1]
111  
ADCY5; adenylate cyclase 5 [KO:K08045] [EC:4.6.1.1]
112  
ADCY6; adenylate cyclase 6 [KO:K08046] [EC:4.6.1.1]
113  
ADCY7; adenylate cyclase 7 [KO:K08047] [EC:4.6.1.1]
114  
ADCY8; adenylate cyclase 8 (brain) [KO:K08048] [EC:4.6.1.1]
115  
ADCY9; adenylate cyclase 9 [KO:K08049] [EC:4.6.1.1]
5566  
PRKACA; protein kinase, cAMP-dependent, catalytic, alpha [KO:K04345] [EC:2.7.11.11]
5567  
PRKACB; protein kinase, cAMP-dependent, catalytic, beta [KO:K04345] [EC:2.7.11.11]
5568  
PRKACG; protein kinase, cAMP-dependent, catalytic, gamma [KO:K04345] [EC:2.7.11.11]
5613  
PRKX; protein kinase, X-linked [KO:K04345] [EC:2.7.11.11]
2912  
GRM2; glutamate receptor, metabotropic 2 [KO:K04605]
2913  
GRM3; glutamate receptor, metabotropic 3 [KO:K04605]
2914  
GRM4; glutamate receptor, metabotropic 4 [KO:K04607]
2916  
GRM6; glutamate receptor, metabotropic 6 [KO:K04608]
2917  
GRM7; glutamate receptor, metabotropic 7 [KO:K04608]
2918  
GRM8; glutamate receptor, metabotropic 8 [KO:K04608]
2770  
GNAI1; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 1 [KO:K04630]
2773  
GNAI3; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 3 [KO:K04630]
2771  
GNAI2; guanine nucleotide binding protein (G protein), alpha inhibiting activity polypeptide 2 [KO:K04630]
2775  
GNAO1; guanine nucleotide binding protein (G protein), alpha activating activity polypeptide O [KO:K04534]
2782  
GNB1; guanine nucleotide binding protein (G protein), beta polypeptide 1 [KO:K04536]
2783  
GNB2; guanine nucleotide binding protein (G protein), beta polypeptide 2 [KO:K04537]
2784  
GNB3; guanine nucleotide binding protein (G protein), beta polypeptide 3 [KO:K07825]
59345  
GNB4; guanine nucleotide binding protein (G protein), beta polypeptide 4 [KO:K04538]
10681  
GNB5; guanine nucleotide binding protein (G protein), beta 5 [KO:K04539]
54331  
GNG2; guanine nucleotide binding protein (G protein), gamma 2 [KO:K07826]
2785  
GNG3; guanine nucleotide binding protein (G protein), gamma 3 [KO:K04540]
2786  
GNG4; guanine nucleotide binding protein (G protein), gamma 4 [KO:K04541]
2787  
GNG5; guanine nucleotide binding protein (G protein), gamma 5 [KO:K04542]
2788  
GNG7; guanine nucleotide binding protein (G protein), gamma 7 [KO:K04543]
94235  
GNG8; guanine nucleotide binding protein (G protein), gamma 8 [KO:K04544]
2790  
GNG10; guanine nucleotide binding protein (G protein), gamma 10 [KO:K04545]
2791  
GNG11; guanine nucleotide binding protein (G protein), gamma 11 [KO:K04546]
55970  
GNG12; guanine nucleotide binding protein (G protein), gamma 12 [KO:K04347]
648044  
guanine nucleotide binding protein (G protein); K04347 guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-12 [KO:K04347]
51764  
GNG13; guanine nucleotide binding protein (G protein), gamma 13 [KO:K04547]
2792  
GNGT1; guanine nucleotide binding protein (G protein), gamma transducing activity polypeptide 1 [KO:K04548]
2793  
GNGT2; guanine nucleotide binding protein (G protein), gamma transducing activity polypeptide 2 [KO:K04549]
156  
ADRBK1; adrenergic, beta, receptor kinase 1 [KO:K00910] [EC:2.7.11.15]
157  
ADRBK2; adrenergic, beta, receptor kinase 2 [KO:K00910] [EC:2.7.11.15]
3760  
KCNJ3; potassium inwardly-rectifying channel, subfamily J, member 3 [KO:K04997]
773  
CACNA1A; calcium channel, voltage-dependent, P/Q type, alpha 1A subunit [KO:K04344]
6506  
SLC1A2; solute carrier family 1 (glial high affinity glutamate transporter), member 2 [KO:K05613]
6512  
SLC1A7; solute carrier family 1 (glutamate transporter), member 7 [KO:K05618]
6505  
SLC1A1; solute carrier family 1 (neuronal/epithelial high affinity glutamate transporter, system Xag), member 1 [KO:K05612]
6511  
SLC1A6; solute carrier family 1 (high affinity aspartate/glutamate transporter), member 6 [KO:K05617]
775  
CACNA1C; calcium channel, voltage-dependent, L type, alpha 1C subunit [KO:K04850]
776  
CACNA1D; calcium channel, voltage-dependent, L type, alpha 1D subunit [KO:K04851]
6507  
SLC1A3; solute carrier family 1 (glial high affinity glutamate transporter), member 3 [KO:K05614]
2752  
GLUL; glutamate-ammonia ligase [KO:K01915] [EC:6.3.1.2]
10991  
SLC38A3; solute carrier family 38, member 3 [KO:K13576]
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
  Authors
Niswender CM, Conn PJ
  Title
Metabotropic glutamate receptors: physiology, pharmacology, and disease.
  Journal
Annu Rev Pharmacol Toxicol 50:295-322 (2010)
Reference
  Authors
Ferraguti F, Crepaldi L, Nicoletti F
  Title
Metabotropic glutamate 1 receptor: current concepts and perspectives.
  Journal
Pharmacol Rev 60:536-81 (2008)
Reference
  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
  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
  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
  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
  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
  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
  Authors
de Jong AP, Verhage M
  Title
Presynaptic signal transduction pathways that modulate synaptic transmission.
  Journal
Curr Opin Neurobiol 19:245-53 (2009)
Reference
  Authors
Pinheiro PS, Mulle C
  Title
Presynaptic glutamate receptors: physiological functions and mechanisms of action.
  Journal
Nat Rev Neurosci 9:423-36 (2008)
Reference
  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
  Authors
Conti F, Weinberg RJ
  Title
Shaping excitation at glutamatergic synapses.
  Journal
Trends Neurosci 22:451-8 (1999)
Reference
  Authors
Sheng M, Kim MJ
  Title
Postsynaptic signaling and plasticity mechanisms.
  Journal
Science 298:776-80 (2002)
KO pathway
 

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