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- Name help_outline H2O Identifier CHEBI:15377 (Beilstein: 3587155; CAS: 7732-18-5) help_outline Charge 0 Formula H2O InChIKeyhelp_outline XLYOFNOQVPJJNP-UHFFFAOYSA-N SMILEShelp_outline [H]O[H] 2D coordinates Mol file for the small molecule Search links Involved in 6,204 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline N-(4-oxoglutaryl)-L-cysteinylglycine Identifier CHEBI:138256 Charge -2 Formula C10H12N2O7S InChIKeyhelp_outline PMIVQUCENWNWHX-YFKPBYRVSA-L SMILEShelp_outline [O-]C(CNC([C@@H](NC(CCC(C([O-])=O)=O)=O)CS)=O)=O 2D coordinates Mol file for the small molecule Search links Involved in 1 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline 2-oxoglutarate Identifier CHEBI:16810 (Beilstein: 3664503; CAS: 64-15-3) help_outline Charge -2 Formula C5H4O5 InChIKeyhelp_outline KPGXRSRHYNQIFN-UHFFFAOYSA-L SMILEShelp_outline [O-]C(=O)CCC(=O)C([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 425 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
- Name help_outline L-cysteinylglycine Identifier CHEBI:61694 Charge 0 Formula C5H10N2O3S InChIKeyhelp_outline ZUKPVRWZDMRIEO-VKHMYHEASA-N SMILEShelp_outline [NH3+][C@@H](CS)C(=O)NCC([O-])=O 2D coordinates Mol file for the small molecule Search links Involved in 4 reaction(s) Find molecules that contain or resemble this structure Find proteins in UniProtKB for this molecule
Cross-references
| RHEA:54532 | RHEA:54533 | RHEA:54534 | RHEA:54535 | |
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| Reaction direction help_outline | undefined | left-to-right | right-to-left | bidirectional |
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Publications
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Nit1 is a metabolite repair enzyme that hydrolyzes deaminated glutathione.
Peracchi A., Veiga-da-Cunha M., Kuhara T., Ellens K.W., Paczia N., Stroobant V., Seliga A.K., Marlaire S., Jaisson S., Bommer G.T., Sun J., Huebner K., Linster C.L., Cooper A.J.L., Van Schaftingen E.
The mammalian gene <i>Nit1</i> (nitrilase-like protein 1) encodes a protein that is highly conserved in eukaryotes and is thought to act as a tumor suppressor. Despite being ∼35% sequence identical to ω-amidase (Nit2), the Nit1 protein does not hydrolyze efficiently α-ketoglutaramate (a known phys ... >> More
The mammalian gene <i>Nit1</i> (nitrilase-like protein 1) encodes a protein that is highly conserved in eukaryotes and is thought to act as a tumor suppressor. Despite being ∼35% sequence identical to ω-amidase (Nit2), the Nit1 protein does not hydrolyze efficiently α-ketoglutaramate (a known physiological substrate of Nit2), and its actual enzymatic function has so far remained a puzzle. In the present study, we demonstrate that both the mammalian Nit1 and its yeast ortholog are amidases highly active toward deaminated glutathione (dGSH; i.e., a form of glutathione in which the free amino group has been replaced by a carbonyl group). We further show that <i>Nit1</i>-KO mutants of both human and yeast cells accumulate dGSH and the same compound is excreted in large amounts in the urine of <i>Nit1</i>-KO mice. Finally, we show that several mammalian aminotransferases (transaminases), both cytosolic and mitochondrial, can form dGSH via a common (if slow) side-reaction and provide indirect evidence that transaminases are mainly responsible for dGSH formation in cultured mammalian cells. Altogether, these findings delineate a typical instance of metabolite repair, whereby the promiscuous activity of some abundant enzymes of primary metabolism leads to the formation of a useless and potentially harmful compound, which needs a suitable "repair enzyme" to be destroyed or reconverted into a useful metabolite. The need for a dGSH repair reaction does not appear to be limited to eukaryotes: We demonstrate that Nit1 homologs acting as excellent dGSH amidases also occur in <i>Escherichia coli</i> and other glutathione-producing bacteria. << Less
Proc. Natl. Acad. Sci. U.S.A. 114:E3233-E3242(2017) [PubMed] [EuropePMC]
This publication is cited by 1 other entry.