KEGG   PATHWAY: ko04724
ko04724                     Pathway                                
Glutamatergic synapse
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.
Organismal Systems; Nervous system
Pathway map
ko04724  Glutamatergic synapse

D02546  Kainic acid hydrate (JP18)
Other DBs
GO: 0051966
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:]
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  serine/threonine-protein phosphatase 2B catalytic subunit [EC:]
K06268  serine/threonine-protein phosphatase 2B 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:]
K02677  classical protein kinase C alpha type [EC:]
K19662  classical protein kinase C beta type [EC:]
K19663  classical protein kinase C gamma type [EC:]
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:]
K01115  phospholipase D1/2 [EC:]
K04371  mitogen-activated protein kinase 1/3 [EC:]
K04632  guanine nucleotide-binding protein G(s) subunit alpha
K08041  adenylate cyclase 1 [EC:]
K08042  adenylate cyclase 2 [EC:]
K08043  adenylate cyclase 3 [EC:]
K08044  adenylate cyclase 4 [EC:]
K08045  adenylate cyclase 5 [EC:]
K08046  adenylate cyclase 6 [EC:]
K08047  adenylate cyclase 7 [EC:]
K08048  adenylate cyclase 8 [EC:]
K08049  adenylate cyclase 9 [EC:]
K04345  protein kinase A [EC:]
K04605  metabotropic glutamate receptor 2
K04606  metabotropic glutamate receptor 3
K04607  metabotropic glutamate receptor 4
K04608  metabotropic glutamate receptor 6
K04609  metabotropic glutamate receptor 7
K04610  metabotropic glutamate receptor 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:]
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 glutamate/aspartate 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:]
K13576  solute carrier family 38 (sodium-coupled neutral amino acid transporter), member 3
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
Niswender CM, Conn PJ
Metabotropic glutamate receptors: physiology, pharmacology, and disease.
Annu Rev Pharmacol Toxicol 50:295-322 (2010)
Ferraguti F, Crepaldi L, Nicoletti F
Metabotropic glutamate 1 receptor: current concepts and perspectives.
Pharmacol Rev 60:536-81 (2008)
Hermans E, Challiss RA
Structural, signalling and regulatory properties of the group I metabotropic glutamate receptors: prototypic family C G-protein-coupled receptors.
Biochem J 359:465-84 (2001)
Kim CH, Lee J, Lee JY, Roche KW
Metabotropic glutamate receptors: phosphorylation and receptor signaling.
J Neurosci Res 86:1-10 (2008)
Meador-Woodruff JH, Clinton SM, Beneyto M, McCullumsmith RE
Molecular abnormalities of the glutamate synapse in the thalamus in schizophrenia.
Ann N Y Acad Sci 1003:75-93 (2003)
Sanacora G, Zarate CA, Krystal JH, Manji HK
Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders.
Nat Rev Drug Discov 7:426-37 (2008)
Gass JT, Olive MF
Glutamatergic substrates of drug addiction and alcoholism.
Biochem Pharmacol 75:218-65 (2008)
Palmada M, Centelles JJ
Excitatory amino acid neurotransmission. Pathways for metabolism, storage and reuptake of glutamate in brain.
Front Biosci 3:d701-18 (1998)
Schoepp DD
Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system.
J Pharmacol Exp Ther 299:12-20 (2001)
de Jong AP, Verhage M
Presynaptic signal transduction pathways that modulate synaptic transmission.
Curr Opin Neurobiol 19:245-53 (2009)
Pinheiro PS, Mulle C
Presynaptic glutamate receptors: physiological functions and mechanisms of action.
Nat Rev Neurosci 9:423-36 (2008)
Byrnes KR, Loane DJ, Faden AI
Metabotropic glutamate receptors as targets for multipotential treatment of neurological disorders.
Neurotherapeutics 6:94-107 (2009)
Conti F, Weinberg RJ
Shaping excitation at glutamatergic synapses.
Trends Neurosci 22:451-8 (1999)
Sheng M, Kim MJ
Postsynaptic signaling and plasticity mechanisms.
Science 298:776-80 (2002)
ko00020  Citrate cycle (TCA cycle)
ko04020  Calcium signaling pathway
ko04720  Long-term potentiation
ko04721  Synaptic vesicle cycle
ko04730  Long-term depression

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