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Glutamate Carboxypeptidase II (N-Acetylaspartylglutamate Peptidase)

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A metallocarboxypeptidase that is predominantly expressed as a membrane-bound enzyme. It catalyzes the hydrolysis of an unsubstituted, C-terminal glutamyl residue, typically from PTEROYLPOLYGLUTAMIC ACIDS. It was formerly classified as EC 3.4.19.8.

Also Known As:

N-Acetylaspartylglutamate Peptidase; FOLH1 Protein; Folate Hydrolase I; N-Acetylated-alpha-Linked Acidic Dipeptidase; NAAG Peptidase; NAALADase; NAALADase II; NAALADase L; Acidic Dipeptidase, N-Acetylated-alpha-Linked; Carboxypeptidase II, Glutamate; Dipeptidase, N-Acetylated-alpha-Linked Acidic; Hydrolase I, Folate; N Acetylaspartylglutamate Peptidase; N Acetylated alpha Linked Acidic Dipeptidase; Peptidase, N-Acetylaspartylglutamate

Networked: 100 relevant articles (8 outcomes, 12 trials/studies)

Relationship Network

Bio-Agent Context: Research Results

Enzymes and Coenzymes
- Enzymes: 34502
  - Hydrolases: 639
    - Peptide Hydrolases: 7577
      - Metalloproteases: 2318
        Metalloexopeptidases: 2
        Glutamate Carboxypeptidase II: 100
        human glutamate carboxypeptidase II: 578
        mouse Glutamate carboxypeptidase III
      - Exopeptidases: 50
        Carboxypeptidases: 21
        Glutamate Carboxypeptidase II: 100
        human glutamate carboxypeptidase II: 578
        mouse Glutamate carboxypeptidase III
        Metalloexopeptidases: 2
        Glutamate Carboxypeptidase II: 100
        human glutamate carboxypeptidase II: 578
        mouse Glutamate carboxypeptidase III

Experts

1.	Slusher, Barbara S: 14 articles (09/2013 - 02/2002)
2.	Neale, Joseph H: 13 articles (07/2015 - 05/2004)
3.	Zhou, Jia: 7 articles (06/2013 - 05/2004)
4.	Olszewski, Rafal T: 7 articles (02/2013 - 05/2004)
5.	Kutala, Vijay Kumar: 6 articles (11/2015 - 04/2012)
6.	Naushad, Shaik Mohammad: 6 articles (11/2015 - 04/2012)
7.	Konvalinka, Jan: 6 articles (05/2015 - 06/2004)
8.	Rojas, Camilo: 6 articles (09/2013 - 08/2003)
9.	Bzdega, Tomasz: 6 articles (02/2013 - 05/2004)
10.	Pomper, Martin G: 6 articles (12/2012 - 04/2002)

Related Diseases

1.	Schizophrenia (Dementia Praecox) 05/01/2009 - "Taken together, these findings do not support a rationale for targeting NAALADase and increasing extracellular NAAG levels as a therapeutic strategy for the treatment of schizophrenia." 05/01/2009 - "Hence, elevating the concentration of endogenous NAAG by inhibition of NAALADase represents a potential strategy for the treatment of schizophrenia via group II mGluR activation. " 02/01/2008 - "Experimental evidence is beginning to converge on an important role for dysregulation of glutamate carboxypeptidase II (GCPII) in schizophrenia. " 05/01/2004 - "These data support the view that NAAG peptidase inhibitors may represent a new therapeutic approach to some of the components of schizophrenia that are modeled by PCP." 05/01/2004 - "NAAG peptidase inhibition reduces locomotor activity and some stereotypes in the PCP model of schizophrenia via group II mGluR."
2.	Prostatic Neoplasms (Prostate Cancer) 10/01/2013 - "Glutamate carboxypeptidase II (GCPII) haplotypes were found to influence susceptibility to prostate cancer. " 03/01/2013 - "Association of glutamate carboxypeptidase II (GCPII) haplotypes with breast and prostate cancer risk." 04/15/2012 - "Glutamate carboxypeptidase II (GCPII) is predominantly expressed in brain, intestinal mucosa and prostate cancer in the form of three splice variants i.e. " 03/22/2006 - "Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer." 07/15/2002 - "These aptamers may be used clinically as NAALADase inhibitors or be modified to carry imaging agents and therapeutic agents directed to prostate cancer cells."
3.	Nervous System Diseases (Neurological Disorders) 09/01/2013 - "Glutamate carboxypeptidase II (GCP II) is a therapeutic target in neurologic disorders associated with excessive activation of glutamatergic systems. " 02/15/2013 - "Inhibition of glutamate carboxypeptidase II enhances recognition memory, a therapeutic action that might be useful in treatment of memory deficits related to age and neurological disorders." 09/01/2012 - "Glutamate carboxypeptidase II (GCPII) is an important target for therapeutic and diagnostic interventions aimed at prostate cancer and neurologic disorders. " 01/01/2012 - "Glutamate carboxypeptidase II in diagnosis and treatment of neurologic disorders and prostate cancer." 04/01/2011 - "Glutamate carboxypeptidase II (GCP2) is a membrane-bound cell-surface peptidase which is implicated in several neurological disorders and is also over-expressed in prostate tumor cells. "
4.	Ischemia 10/06/2000 - "N-acetylated-alpha-linked-acidic dipeptidase inhibitor has a neuroprotective effect on mouse retinal ganglion cells after pressure-induced ischemia." 12/01/1999 - "Consistent with inhibition of NAALADase, we show that 2-PMPA increases NAAG and attenuates the ischemia-induced rise in glutamate. " 09/14/2001 - "2-Phosphonomethyl pentanedioic acid (2-PMPA) is a potent and selective inhibitor of glutamate carboxypeptidase II (NAALADase), and has shown robust neuroprotective activity in both in vitro and in vivo models of ischemia. " 02/15/2002 - "Since ischemia is believed to be a prominent mechanism involved in diabetic polyneuropathy (DPN), we investigated the effect of the glutamate carboxypeptidase II (GCPII, EC #3.4-17.21; previously termed NAALADase), an enzyme responsible for the hydrolysis of the neuropeptide NAAG to NAA and glutamate, on the development of DPN in type 1 diabetic BB/Wor rats. " 02/22/2002 - "While L(+)-2-Amino-4-phosphonobutyric acid (L-AP4) and trans-[1S,3R]-1-Amino-cyclopentane-1, 3-dicarboxylic acid (t-ACPD) were unable to provide protection against hypoxic-ischemic brain injury, 2-(phosphonomethyl) pentanedioic acid (2-PMPA), an inhibitor of N-acetylated alpha-linked acidic dipeptidase (NAALADase), which hydrolyzes endogenous NAAG into N-acetyl-aspartate and glutamate, significantly reduced neonatal hypoxia-ischemia-induced brain injury. "
5.	Brain Injuries (Brain Injury) 07/01/2015 - "Mice lacking glutamate carboxypeptidase II develop normally, but are less susceptible to traumatic brain injury." 10/01/2005 - "Mice lacking glutamate carboxypeptidase II are protected from peripheral neuropathy and ischemic brain injury." 12/01/1999 - "Selective inhibition of NAALADase, which converts NAAG to glutamate, reduces ischemic brain injury." 10/01/2001 - "We have evaluated the effects of the N-acetylated-alpha-linked acidic dipeptidase (NAALADase) inhibitor, GPI5232 [2-[(pentafluorophenylmethyl)hydroxyphosphinyl]methyl)-pentanedioic acid], to not only decrease brain injury but also to alter the inherent electroencephalographic (EEG) changes observed in a rat model of transient middle cerebral artery occlusion (MCAo). " 02/22/2002 - "While L(+)-2-Amino-4-phosphonobutyric acid (L-AP4) and trans-[1S,3R]-1-Amino-cyclopentane-1, 3-dicarboxylic acid (t-ACPD) were unable to provide protection against hypoxic-ischemic brain injury, 2-(phosphonomethyl) pentanedioic acid (2-PMPA), an inhibitor of N-acetylated alpha-linked acidic dipeptidase (NAALADase), which hydrolyzes endogenous NAAG into N-acetyl-aspartate and glutamate, significantly reduced neonatal hypoxia-ischemia-induced brain injury. "

Related Drugs and Biologics

1.	Glutamic Acid (Glutamate)
2.	Glutamate Carboxypeptidase II (N-Acetylaspartylglutamate Peptidase)
3.	2-(phosphonomethyl)pentanedioic acid
4.	metabotropic glutamate receptor 3 (mGluR3)
5.	Dizocilpine Maleate (Dizocilpine)
6.	metabotropic glutamate receptor 2
7.	Excitatory Amino Acid Agonists
8.	N-acetylaspartate (N-acetyl aspartate)
9.	Urea (Carbamide)
10.	Ligands

Related Therapies and Procedures

1.	Sutures (Suture)
2.	Therapeutics
3.	Drug Therapy (Chemotherapy)
4.	Analgesia