Nitrilase 1 (NIT1)

Nitrilase 1 (NIT1) is an enzyme belonging to the nitrilase protein family, best characterized as a deaminated glutathione amidase or metabolite repair enzyme. NIT1 hydrolyzes deaminated glutathione (dGSH), a potentially harmful metabolite produced as a side product of transaminase activity, thereby preventing its accumulation and contributing to cellular detoxification and maintenance of glutathione homeostasis. NIT1 is highly conserved across eukaryotes, localizes to both mitochondria and cytosol, and is implicated in tumor suppression through interactions with proteins such as Fhit and the TGFβ–Smad2/3 signaling pathway. Reduced expression of NIT1 is associated with more aggressive tumor properties in colorectal cancer; however, its role in cancer can be context-dependent, influencing both tumor growth and chemosensitivity in different tissues. No drugs are currently known to target NIT1 directly, and no significant toxicities are linked to its modulation, though its deficiency leads to unique metabolic perturbations.

Other names

Deaminated glutathione amidasedGSH amidaseNitrilase homolog 1

Hydrolysis of deaminated glutathione (dGSH), a damaging side-product of transaminase activity, to prevent accumulation and cellular toxicity. Potential interaction with tumor suppressor pathways (via physical interaction with Fhit protein and recruitment of Smad2/3 to TGFβ receptors).