Application | Comment | Organism |
---|---|---|
medicine | rationale for enzyme KMO inhibition as a therapeutic strategy to protect against acute kidney injury (AKI) during critical illness. Renal ischemia-reperfusion injury (IRI) is a leading cause of acute kidney injury (AKI) | Mus musculus |
Cloned (Comment) | Organism |
---|---|
gene kmo, quantitative real-time PCR enzyme expression analysis | Mus musculus |
Protein Variants | Comment | Organism |
---|---|---|
additional information | generation of enzyme knockout mutant mice, which are engineered on a C57BL/6 background to lack KMO activity by insertion of a polyA transcription stop motif before exon 5 of the Kmo gene (Kmotm1a(KOMP)Wtsi). Kmonull mice are unable to form 3-hydroxykynurenine. Kmonull mice are protected against AKI after renal ischemia-reperfusion injury (IRI). KMO deletion inhibits neutrophil infiltration in the kidney following IRI. Mutant mouse phenotype, detailed overview | Mus musculus |
Localization | Comment | Organism | GeneOntology No. | Textmining |
---|---|---|---|---|
mitochondrial outer membrane | - |
Mus musculus | 5741 | - |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
L-kynurenine + NADPH + H+ + O2 | Mus musculus | - |
3-hydroxy-L-kynurenine + NADP+ + H2O | - |
? | |
L-kynurenine + NADPH + H+ + O2 | Mus musculus C57BL/6N x C57BL/6J | - |
3-hydroxy-L-kynurenine + NADP+ + H2O | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Mus musculus | Q91WN4 | - |
- |
Mus musculus C57BL/6N x C57BL/6J | Q91WN4 | - |
- |
Source Tissue | Comment | Organism | Textmining |
---|---|---|---|
kidney | high enzyme expression level | Mus musculus | - |
liver | - |
Mus musculus | - |
renal proximal tubule epithelial cell | - |
Mus musculus | - |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
L-kynurenine + NADPH + H+ + O2 | - |
Mus musculus | 3-hydroxy-L-kynurenine + NADP+ + H2O | - |
? | |
L-kynurenine + NADPH + H+ + O2 | - |
Mus musculus C57BL/6N x C57BL/6J | 3-hydroxy-L-kynurenine + NADP+ + H2O | - |
? |
Synonyms | Comment | Organism |
---|---|---|
KMO | - |
Mus musculus |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Mus musculus |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.4 | - |
assay at | Mus musculus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
FAD | - |
Mus musculus | |
NADPH | - |
Mus musculus |
General Information | Comment | Organism |
---|---|---|
malfunction | Kmonull mice are unable to form 3-hydroxykynurenine and have preserved renal function, reduced renal tubular cell injury, and fewer infiltrating neutrophils compared with wild-type (Kmowt) control mice. Tubular epithelial cell apoptosis is reduced in the kidney of Kmonull mice following IRI | Mus musculus |
metabolism | the enzyme is involved in the kynurenine pathway of tryptophan metabolism. The conversion of tryptophan to N-formylkynurenine (KYN) is catalyzed by tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenases (IDOs). The kynurenine pathway diverges at kynurenine into two distinct branches that are regulated by kynurenine aminotransferases (KATs) and kynurenine 3-monooxygenase (KMO), respectively | Mus musculus |
physiological function | kynurenine 3-monooxygenase is a critical regulator of renal ischemia-reperfusion injury. Flux through KMO contributes to acute kidney injury (AKI) after ischemia-reperfusion injury (IRI), and supports the rationale for KMO inhibition as a therapeutic strategy to protect against AKI during critical illness. KMO is the gate-keeper enzyme. Kynurenine pathway metabolite concentrations in plasma and kidney tissue after ischemia-reperfusion injury (IRI), overview | Mus musculus |