Reactome | NAALADases hydrolyse NAAG

NAALADases hydrolyse NAAG

Stable Identifier

R-HSA-5693783

Type

Reaction [transition]

Species

Homo sapiens

Compartment

plasma membrane

Synonyms

H2O + N-acetyl-L-aspartyl-L-glutamate => L-glutamate + N-acetyl-L-aspartate

ReviewStatus

5/5

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Excessive glutamate has been implicated in neurodegenerative disorders and stroke. One source of glutamate is the hydrolysis of N-acetylaspartylglutamate (NAAG), a neurotransmitter found in the brain. NAAG can be 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
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
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
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