NAALADases hydrolyse NAAG

Stable Identifier
R-HSA-5693783
Type
Reaction [transition]
Species
Homo sapiens
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Excessive glutamate has been implicated in neurodegenerative disorders and stroke. One source of glutamate is from the hydrolysis of N-acetylaspartylglutamate (NAAG), a neurotransmitter found in the brain. NAAG can he hydrolysed by glutamate carboxypeptidase 2 (FOLH1), a membrane-bound, homodimeric enzyme which possesses both folate hydrolase and N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity (Mesters et al. 2006). Inhibition of FOLH1 could have neuroprotective effects (Wozniak et al. 2012). Other dipeptidases able to hydrolyse NAAG are N-acetylated-alpha-linked acidic dipeptidase 2 (NAALAD2) (Pangalos et al. 1999, Hlouchova et al. 2009) and putative N-acetylated-alpha-linked acidic dipeptidase (FOLH1B) (O'Keefe et al. 2004).

Literature References
PubMed ID Title Journal Year
16467855 Structure of glutamate carboxypeptidase II, a drug target in neuronal damage and prostate cancer

Mesters, JR, Barinka, C, Li, W, Tsukamoto, T, Majer, P, Slusher, BS, Konvalinka, J, Hilgenfeld, R

EMBO J. 2006
10085079 Isolation and expression of novel human glutamate carboxypeptidases with N-acetylated alpha-linked acidic dipeptidase and dipeptidyl peptidase IV activity

Pangalos, MN, Neefs, JM, Somers, M, Verhasselt, P, Bekkers, M, van der Helm, L, Fraiponts, E, Ashton, D, Gordon, RD

J Biol Chem 1999
14716746 Comparative analysis of prostate-specific membrane antigen (PSMA) versus a prostate-specific membrane antigen-like gene

O'Keefe, DS, Bacich, DJ, Heston, WD

Prostate 2004
19678840 Structural insight into the evolutionary and pharmacologic homology of glutamate carboxypeptidases II and III

Hlouchova, K, Barinka, C, Konvalinka, J, Lubkowski, J

FEBS J. 2009
22304711 The role of glutamate signaling in pain processes and its regulation by GCP II inhibition

Wozniak, KM, Rojas, C, Wu, Y, Slusher, BS

Curr. Med. Chem. 2012
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Catalyst Activity
Title
dipeptidase activity of NAALADases [plasma membrane]
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