1.14.13.9: kynurenine 3-monooxygenase
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For detailed information about kynurenine 3-monooxygenase, go to the full flat file.
Word Map on EC 1.14.13.9
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1.14.13.9
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mercury
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hg
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kynurenic
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3-hydroxykynurenine
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quinolinic
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2,3-dioxygenase
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kynureninase
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indoleamine
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cronbach
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huntington
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bartlett
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paint
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3-hydroxyanthranilic
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quin
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neuroactive
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ochre
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realgar
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psychometric
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calcite
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methylmercury
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xanthurenic
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eigenvalue
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vermilion
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hematite
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test-retest
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excitotoxins
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ommochrome
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artwork
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geochemical
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indoleamine-2,3-dioxygenase
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archaeological
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varimax
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roman
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mineralogical
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slovenia
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micro-raman
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molecular biology
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medicine
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analysis
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pharmacology
- 1.14.13.9
- mercury
- hg
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kynurenic
- 3-hydroxykynurenine
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quinolinic
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2,3-dioxygenase
- kynureninase
- indoleamine
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cronbach
- huntington
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bartlett
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paint
-
3-hydroxyanthranilic
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quin
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neuroactive
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ochre
-
realgar
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psychometric
-
calcite
- methylmercury
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xanthurenic
-
eigenvalue
-
vermilion
-
hematite
-
test-retest
-
excitotoxins
-
ommochrome
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artwork
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geochemical
- indoleamine-2,3-dioxygenase
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archaeological
-
varimax
-
roman
-
mineralogical
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slovenia
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micro-raman
- molecular biology
- medicine
- analysis
- pharmacology
Reaction
Synonyms
BcKMO, Bna4, cinnabar, EC 1.14.1.2, EC 1.99.1.5, FAD dependent kynurenine 3-monooxygenase, flavin adenine dinucleotide dependent kynurenine 3-monooxygenase, hKMO, Hs-KMO, K3H, KMO, KYN-OHase, kynurenine 3-hydroxylase, kynurenine 3-monooxygenase, kynurenine hydroxylase, kynurenine monooxygenase, kynurenine-3-monooxygenase, L-kynurenine 3-monooxygenase, L-kynurenine,NADPH2:oxygen oxidoreductase (3-hydroxylating), L-kynurenine-3-hydroxylase, More, NADPH-dependent flavin monooxygenase, oxygenase, kynurenine 3-mono-, pfKMO, Rat-KMO, scKMO
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General Information
General Information on EC 1.14.13.9 - kynurenine 3-monooxygenase
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drug target
evolution
malfunction
metabolism
physiological function
additional information
contents of L-tryptophan and monoamines and their metabolites are measured in the serum and hippocampus of kynurenine 3-monooxygenase KO mice. It is investigated whether antidepressants improve the depressive-like behaviors in kynurenine 3-monooxygenase KO mice. KO mice show antidepressants-responsive depressive-like behaviors and monoaminergic dysfunctions via abnormality of kynurenine metabolism with good validities as model for major depressive disorder
drug target
inhibition of the enzyme shows benefit in neurodegenerative diseases such as Huntingtons and Alzheimers. It is a target for acute pancreatitis multiple organ dysfunction syndrome
drug target
kynurenine represents a branch point of the kynurenine pathway, being converted into the neurotoxin 3-hydroxykynurenine via kynurenine monooxygenase, neuroprotectant kynurenic acid, and anthranilic acid. As a result of this branch point, kynurenine monooxygenase is an attractive drug target for several neurodegenerative and/or neuroinflammatory diseases, especially Huntington's, Alzheimer's, and Parkinson's diseases
drug target
the enzyme is a clinical candidate for the treatment of acute pancreatitis
drug target
the enzyme is a potential drug target for treatment of neurodegenerative disorders such as Huntington's and Alzheimer's diseases
drug target
the enzyme is a potential therapeutic target for neurodegenerative and neurologic disorders
drug target
the enzyme is a therapeutic target in several disease states, including Huntington's disease
KMO belongs to a family of NAD(P)H-dependent flavin monooxygenase (FMO). KMO has one dicucleotide binding domain, which simply categorizes it as a Class A flavoprotein aromatic hydroxylase
evolution
KMO belongs to a family of NAD(P)H-dependent flavin monooxygenase (FMO). KMO has one dicucleotide binding domain, which simply categorizes it as a Class A flavoprotein aromatic hydroxylase
evolution
KMO belongs to a family of NAD(P)H-dependent flavin monooxygenase (FMO). KMO has one dicucleotide binding domain, which simply categorizes it as a Class A flavoprotein aromatic hydroxylase
evolution
KMO belongs to a family of NAD(P)H-dependent flavin monooxygenase (FMO). KMO has one dicucleotide binding domain, which simply categorizes it as a Class A flavoprotein aromatic hydroxylase
evolution
KMO is a class A external flavoprotein aromatic hydroxylase (FAH). This class of enzymes uses the isoalloxazine ring of FAD to mediate the delivery of electrons from singlet state NADPH to the molecular oxygen ground state triplet in order to promote subsequent hydroxylation of singlet state molecules
adaptiveand possibly regulatory-changes in mice with a targeted deletion of kynurenine 3-monooxygenase (Kmo-/-) are investigated kynurenine 3-monooxygenase-deficient mice are characterized using six behavioral assays relevant for the study of schizophrenia. Elimination of kynurenine 3-monooxygenase in mice is associated with multiple gene and functional alterations that appear to duplicate aspects of the psychopathology of several neuropsychiatric disorder
malfunction
contents of L-tryptophan and monoamines and their metabolites are measured in the serum and hippocampus of kynurenine 3-monooxygenase KO mice. It is investigated whether antidepressants improve the depressive-like behaviors in kynurenine 3-monooxygenase KO mice. A deficiency in kynurenine 3-monooxygenase appears to be implicated in antidepressant-responsive depression-like behaviors. In the kynurenine 3-monooxygenase KO mice, there are abnormal kynurenine pathway metabolites and monoamines. The abnormal monoamines in addition to the abnormal kynurenine pathway metabolites may play an important role in the pathophysiology of major depressive disorder
malfunction
human polymorphism in the C-terminal region of the enzyme results in an Arg452Cys mutation, statistically linked to bipolar disorder and schizophrenia
malfunction
the white egg 1 (w-1) mutant, which is characterized by white eyes and white eggs, is deficient in Bombyx kynurenine 3-monooxygenase activity. To investigate whether the w-1 mutant phenotype is rescued by introducing the wild-type kynurenine 3-monooxygenase gene, transgenic silkworms with the wild-type Bombyx kynurenine 3-monooxygenase gene under the control of either the cytoplasmic actin gene promoter or the native kynurenine 3-monooxygenase gene promoter are constructed. The results indicate that the wild-type kynurenine 3-monooxygenase gene can be used as a marker gene for visually screening transgenic silkworms
malfunction
diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous lymphoid malignancy and a clinically heterogeneous lymphoid malignancy that is the most common type of lymphoma in Japan, patients with DLBCL have a poor progxadnosis due to increased levels of indoleamine 2,3-dioxygnase and kynurenine (KYN). Serum 3-hydroxy-L-kynurenine (3-HK) levels are regulated independently of serum KYN levels, and increased serum 3-HK levels and KMO activity are associated with worse disease progression. The addition of KMO inhibitors and 3-HK negatively and positively regulate the viability of DLBCL cells, respectively. NAD+ levels in high-KMO-expression-level KMOhigh STR-428 cells are significantly higher than those in low-KMO-expression-level KMOlow KML-1 cells. These results suggest that 3-HK generated by KMO activity may be involved in the regulation of DLBCL cell viability via NAD+ synthesis
malfunction
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enzyme BcKMO deficiency reduces the resistance of Bortrytis cinerea to osmotic stress, suggesting a positive regulatory role of this gene in osmotic stress resistance in Bortrytis cinerea. A similar trend is also noted with respect to the inhibition rate. The cellular integrity is enhanced in the mutant BCG183
malfunction
KMO is downregulated in autografts and is almost completely silenced in allograft rejection
malfunction
KMO is downregulated in autografts and is almost completely silenced in allograft rejection
malfunction
kmo-/- mice are vulnerable to pathogenic viral challenge with severe clinical symptoms. HSV-1 replication is significantly enhanced in KMO-knockdown cells compared to wild-type cells. Mutant kmo-/- mice are more susceptible to viral infections
malfunction
KMO-deficient Drosophila melanogaster shows mitochondrial phenotypes in vitro and in vivo, overview. Loss of function allele or RNAi knockdown of the Drosophila KMO orthologue gene cinnabar causes a range of morphological and functional alterations to mitochondria, which are independent of changes to levels of KP metabolites. Elongated mitochondria are observed in cinnabar deficient fly models. Mitochondrial DRP1 Ser637 phosphorylation is reduced by KMO overexpression, resulting in an increase in mitochondrial fission
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
malfunction
kynurenine monooxygenase (KMO) is the ideal target for an inhibitor because its inhibition is expected to reduce the toxic metabolites and increase kynurenic acid (KYNA), which is neuroprotective. KMO inhibitors can correct the 3-HK/KYNA unbalance
malfunction
kynurenine-3-monooxygenase (KMO) is an important therapeutic target for several brain disorders. Potent inhibitors of KMO within different disease models show great therapeutic potential, especially in models of neurodegenerative disease. The inhibition of KMO reduces the production of downstream toxic kynurenine pathway metabolites and shifts the flux to the formation of the neuroprotectant kynurenic acid
malfunction
kynurenine-3-monooxygenase (KMO) is an important therapeutic target for several brain disorders. Potent inhibitors of KMO within different disease models show great therapeutic potential, especially in models of neurodegenerative disease. The inhibition of KMO reduces the production of downstream toxic kynurenine pathway metabolites and shifts the flux to the formation of the neuroprotectant kynurenic acid
malfunction
kynurenine-3-monooxygenase (KMO) is an important therapeutic target for several brain disorders. Potent inhibitors of KMO within different disease models show great therapeutic potential, especially in models of neurodegenerative disease. The inhibition of KMO reduces the production of downstream toxic kynurenine pathway metabolites and shifts the flux to the formation of the neuroprotectant kynurenic acid
malfunction
mutations at the dimeric interface abolish the enzyme activity
malfunction
mutations at the dimeric interface abolish the enzyme activity
malfunction
Neurons contain a large proportion of functional KMO in the adult mouse brain under both physiological and pathological conditions. Both KMO expression and function have been reported to be upregulated in neurons in a mouse model of neuropathic pain
malfunction
neuroprotection of KMO inhibition through accumulation of kynureninic acid (KYNA) has neuroprotective effects and results in attenuation of NMDA receptor function
malfunction
the dysregulation of the kynurenine pathway and increased levels of toxic metabolites have been implicated in various disease states, including neurological disorders such as Huntington's disease (HD), Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) epilepsy, affective disorders schizophrenia, depression, and anxiety, autoimmune related diseases rheumatoid arthritis (RA), multiple sclerosis (MS), and HIV-related dementia, peripheralconditions such as cardiovascular disease and ischemic stroke, and malignancies such as hematological neoplasia and colorectal cancer. The inhibition of KMO is a potential therapeutic strategy to rebalance the KP in hopes of mitigating and/or preventing disease progression since it sits at the key branching point of the KP. Inhibiting KMO will not only decrease the levels of toxic metabolites 3-HK and QUIN, but also increase the levels of the neuroprotective KYNA available for metabolism by kynurenine aminotransferase. Mechanisms, overview
malfunction
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kynurenine monooxygenase (KMO) is the ideal target for an inhibitor because its inhibition is expected to reduce the toxic metabolites and increase kynurenic acid (KYNA), which is neuroprotective. KMO inhibitors can correct the 3-HK/KYNA unbalance
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malfunction
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KMO-deficient Drosophila melanogaster shows mitochondrial phenotypes in vitro and in vivo, overview. Loss of function allele or RNAi knockdown of the Drosophila KMO orthologue gene cinnabar causes a range of morphological and functional alterations to mitochondria, which are independent of changes to levels of KP metabolites. Elongated mitochondria are observed in cinnabar deficient fly models. Mitochondrial DRP1 Ser637 phosphorylation is reduced by KMO overexpression, resulting in an increase in mitochondrial fission
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malfunction
Botrytis cinerea BC22
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enzyme BcKMO deficiency reduces the resistance of Bortrytis cinerea to osmotic stress, suggesting a positive regulatory role of this gene in osmotic stress resistance in Bortrytis cinerea. A similar trend is also noted with respect to the inhibition rate. The cellular integrity is enhanced in the mutant BCG183
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malfunction
Mus musculus C57BL/6N x C57BL/6J
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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
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enzyme of the kynurenine pathway, which is the major catabolic route of tryptophan
metabolism
the enzyme is central to the kynurenine pathway of tryptophan metabolism
metabolism
the enzyme is involved in kynurenine pathway. It catalyzes the decisive step in production of metabolites as quinolinic acid
metabolism
the enzyme is very important in kynurenine pathway because it catalyzes the decisive step in production of metabolites as quinolinic acid
metabolism
enzyme kynurenine 3-monooxygenase (KMO) operates at a critical branch-point in the kynurenine pathway (KP), the major route of tryptophan metabolism. KMO modulates DRP1 post-translational regulation
metabolism
FAD-dependent kynurenine 3-monooxygenase (KMO) catalyzes the conversion of L-kynurenine (L-Kyn) to 3-Hydroxykynurenine (3-HK) in the kynurenine pathway. In the pathway responsible for the catabolism of tryptophan, enzyme KMO regulates the levels of bioactive substances. L-Kyn, is also a substrate to both kynureninase (KYNU) and especially to kynurenine aminotransferase (KAT), which converts L-Kyn to kynurenic acid (KynA), a neuroprotective agent for being the antagonist of NMDA, alpha-7 nicotinic acetylcholine, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate, and an antioxidant for being the scavenger of several free radical species
metabolism
FAD-dependent kynurenine 3-monooxygenase (KMO) catalyzes the conversion of L-kynurenine (L-Kyn) to 3-Hydroxykynurenine (3-HK) in the kynurenine pathway. In the pathway responsible for the catabolism of tryptophan, enzyme KMO regulates the levels of bioactive substances. L-Kyn, is also a substrate to both kynureninase (KYNU) and especially to kynurenine aminotransferase (KAT), which converts L-Kyn to kynurenic acid (KynA), a neuroprotective agent for being the antagonist of NMDA, alpha-7 nicotinic acetylcholine, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate, and an antioxidant for being the scavenger of several free radical species
metabolism
FAD-dependent kynurenine 3-monooxygenase (KMO) catalyzes the conversion of L-kynurenine (L-Kyn) to 3-Hydroxykynurenine (3-HK) in the kynurenine pathway. In the pathway responsible for the catabolism of tryptophan, enzyme KMO regulates the levels of bioactive substances. L-Kyn, is also a substrate to both kynureninase (KYNU) and especially to kynurenine aminotransferase (KAT), which converts L-Kyn to kynurenic acid (KynA); a neuroprotective agent for being the antagonist of NMDA, alpha-7 nicotinic acetylcholine, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate, and an antioxidant for being the scavenger of several free radical species
metabolism
KMO is an important enzyme in the kynurenine pathway (KP), overview. The KP metabolises more than 95% of TRP. This pathway has been implicated in numerous diseases, including Huntington's disease, Alzheimer's disease, Parkinson's disease, schizophrenia, acute pancreatitis and cancer. L-kynurenine (L-KYN) can be metabolised by three different enzymes and lies at the key branchpoint of the KP. L-KYN can be metabolised to 3-hydroxy-L-kynurenine (3-HK) by KMO, or it can form kynurenic acid (KYNA), by a transamination reaction catalysed by kynurenine aminotransferase II (KATII), or alternatively it can be converted to anthranilic acid (AA) by kynureninase, which then feeds back into the 3-HK branch of the KP. Since KMO has the tightest binding affinity for L-KYN under normal conditions, the KMO branch has been considered to be the major metabolic route of the KP. KMO activity plays an essential role in maintaining a balance between the neurotoxic and neuroprotective potential of the pathway
metabolism
KMO is an important enzyme in the kynurenine pathway (KP), overview. The KP metabolises more than 95% of TRP. This pathway has been implicated in numerous diseases, including Huntington's disease, Alzheimer's disease, Parkinson's disease, schizophrenia, acute pancreatitis and cancer. L-kynurenine (L-KYN) can be metabolised by three different enzymes and lies at the key branchpoint of the KP. L-KYN can be metabolised to 3-hydroxy-L-kynurenine (3-HK) by KMO, or it can form kynurenic acid (KYNA), by a transamination reaction catalysed by kynurenine aminotransferase II (KATII), or alternatively it can be converted to anthranilic acid (AA) by kynureninase, which then feeds back into the 3-HK branch of the KP. Since KMO has the tightest binding affinity for L-KYN under normal conditions, the KMO branch has been considered to be the major metabolic route of the KP. KMO activity plays an essential role in maintaining a balance between the neurotoxic and neuroprotective potential of the pathway
metabolism
KMO is an important enzyme in the kynurenine pathway (KP), overview. The KP metabolises more than 95% of TRP. This pathway has been implicated in numerous diseases, including Huntington's disease, Alzheimer's disease, Parkinson's disease, schizophrenia, acute pancreatitis and cancer. L-kynurenine (L-KYN) can be metabolised by three different enzymes and lies at the key branchpoint of the KP. L-KYN can be metabolised to 3-hydroxy-L-kynurenine (3-HK) by KMO, or it can form kynurenic acid (KYNA), by a transamination reaction catalysed by kynurenine aminotransferase II (KATII), or alternatively it can be converted to anthranilic acid (AA) by kynureninase, which then feeds back into the 3-HK branch of the KP. Since KMO has the tightest binding affinity for L-KYN under normal conditions, the KMO branch has been considered to be the major metabolic route of the KP. KMO activity plays an essential role in maintaining a balance between the neurotoxic and neuroprotective potential of the pathway
metabolism
kynurenine 3-monooxygenase (KMO) catalyzes the conversion of L-kynurenine to 3-hydroxykynurenine (3-HK) in the kynurenine pathway (KP), the major route of tryptophan degradation in eukaryotic organisms
metabolism
kynurenine 3-monooxygenase (KMO) catalyzes the conversion of L-kynurenine to 3-hydroxykynurenine (3-HK) in the kynurenine pathway (KP), the major route of tryptophan degradation in eukaryotic organisms
metabolism
kynurenine 3-monoxygenase (KMO) catalyzes the conversion of L-kynurenine (L-Kyn) to 3-hydroxykynurenine (3-OHKyn) in the pathway for tryptophan catabolism. The KMO active site is insulated from exchange with solvent during catalysis
metabolism
kynurenine-3-monooxygenase (KMO) is a key rate-limiting enzyme in the kynurenine pathway (KP) in tryptophan metabolism. The tryptophan (Trp) metabolism through the kynurenine pathway (KP) is well known to play a critical function in cancer, autoimmune and neurodegenerative diseases
metabolism
the enzyme is involved in the kynurenine pathway (KP) that is the essential metabolic pathway for the catabolism of tryptophan. L-kynurenine (KYN) is the key and first stable intermediate of the KP by a formamidase. There are three possible metabolic fates for KYN, which involve biotransformations with (1) kynurenine aminotransferase (KAT) to form kynurenic acid (KynA), (2) kynureninase to form anthranilic acid, and (3) kynurenine 3-monooxygenase (KMO) to form 3-hydroxykynurnine (3-HK). 3-Hydroxykynurnine (3-HK) further leads to the formation of picolinic acid, 3-HANA, cinnabarinic acid, and quinolinic acid (QUIN). Three metabolites, QUIN, 3-HK, and 3-HANA, have been shown to be neurotoxic
metabolism
the enzyme is involved in the kynurenine pathway (KP) that is the essential metabolic pathway for the catabolism of tryptophan. L-kynurenine (KYN) is the key and first stable intermediate of the KP by a formamidase. There are three possible metabolic fates for KYN, which involve biotransformations with (1) kynurenine aminotransferase (KAT) to form kynurenic acid (KynA), (2) kynureninase to form anthranilic acid, and (3) kynurenine 3-monooxygenase (KMO) to form 3-hydroxykynurnine (3-HK). 3-Hydroxykynurnine (3-HK) further leads to the formation of picolinic acid, 3-HANA, cinnabarinic acid, and quinolinic acid (QUIN). Three metabolites, QUIN, 3-HK, and 3-HANA, have been shown to be neurotoxic
metabolism
the enzyme is involved in the kynurenine pathway (KP) that is the essential metabolic pathway for the catabolism of tryptophan. L-kynurenine (KYN) is the key and first stable intermediate of the KP by a formamidase. There are three possible metabolic fates for KYN, which involve biotransformations with (1) kynurenine aminotransferase (KAT) to form kynurenic acid (KynA), (2) kynureninase to form anthranilic acid, and (3) kynurenine 3-monooxygenase (KMO) to form 3-hydroxykynurnine (3-HK). 3-Hydroxykynurnine (3-HK) further leads to the formation of picolinic acid, 3-HANA, cinnabarinic acid, and quinolinic acid (QUIN). Three metabolites, QUIN, 3-HK, and 3-HANA, have been shown to be neurotoxic
metabolism
the enzyme is involved in the kynurenine pathway (KP) that is the essential metabolic pathway for the catabolism of tryptophan. L-kynurenine (KYN) is the key and first stable intermediate of the KP by a formamidase. There are three possible metabolic fates for KYN, which involve biotransformations with (1) kynurenine aminotransferase (KAT) to form kynurenic acid (KynA), (2) kynureninase to form anthranilic acid, and (3) kynurenine 3-monooxygenase (KMO) to form 3-hydroxykynurnine (3-HK). 3-Hydroxykynurnine (3-HK) further leads to the formation of picolinic acid, 3-HANA, cinnabarinic acid, and quinolinic acid (QUIN). Three metabolites, QUIN, 3-HK, and 3-HANA, have been shown to be neurotoxic. KYNA serves as a neuroprotective agent due to its antagonistic effects at the glutamate receptor and all three subtypes of ionotropic receptors, N-methyl-D-aspartate (NMDA), kainate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA). KYNA selectively binds to a G-protein-coupled receptor, GPR35, leading to its activation. Also, kynurenic acid plays a role in epilepsy and has ability to reduce ischemic brain damage. KYNA also has antioxidant properties, as it can scavenge hydroxyl, superoxide anion, and other free radicals. Patients with schizophrenia presented with elevated kynurenic acid levels in the cerebral spinal fluid. Elevated levels of endogenous kynurenic acid increase the firing activity of midbrain dopamine neurons. This increase alters the effects of both nicotine and clozapine, leading to inhibitory responses of the ventral tegmental area (VTA) dopamine neurons that cause disrupted prepulse inhibition, an effect restored by antipsychotics. Elevated levels of KYNA have also been implicated in rapid progression among lung cancer patients, HIV-related illnesses, cataracts, tick-borne encephalitis, and partial seizures in epileptic patients. Most recently, KYNA has also been associated with antidepressant-like and antimigraine-like effects as well. Other endogenous neuroprotectant metabolites of the kynurenine pathway, detailed overview. Research focuse on the inhibition of key enzymes in the kynurenine pathway (KP) to shunt it towards a neuroprotective state, based on the assumption that kynurenic acid (KYNA) has neuroprotective abilities. Dissimilar to the other neurotoxic metabolites of the kynurenine pathway, the toxic effects of 3-hydroxykynurenine (3-HK) are independent of the NMDA receptor and solely result from the production of free radicals. 3-HK is mostly known for its ability to filter UV light in the human lens and its involvement in cataract formation. 3-HK is a controversial metabolite, while mostly considered neurotoxic, it is also able to act as a scavenger and is involved in immunoregulation. Similar to 3-HK, 3-hydroxyanthranilic acid (3-HANA) has also been shown to play a role in the regulation of the immune system and is believed to scavenge NO radicals. 3-HANA is prone to autooxidation
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
metabolism
the kynurenine pathway (KP) is the principal pathway for the metabolism of tryptophan (TRY) involving the enzyme, pathway overview
metabolism
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enzyme kynurenine 3-monooxygenase (KMO) operates at a critical branch-point in the kynurenine pathway (KP), the major route of tryptophan metabolism. KMO modulates DRP1 post-translational regulation
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metabolism
Mus musculus C57BL/6N x C57BL/6J
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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
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T helper 17 cells preferentially express kynurenine 3-monooxygenase. Enzyme inhibition, either with a specific inhibitor or via siRNA-mediated silencing, markedly increases IL-17 productionin vitro, whereas IFN-gamma production by T helper 1 cells is unaffected. Inhibition of kynurenine 3-monooxygenase significantly exacerbates disease in a Th17-driven model of autoimmune gastritis
physiological function
the white egg 1 mutant, which is characterized by white eyes and white eggs, is deficient in Bombyx kynurenine 3-monooxygenase activity.Expression of the wild-type gene under control of either the cytoplasmic actin gene promoter (A3KMO) or the native KMO gene promoter (KKMO) leads to adults with brown eyes, and the eggs laid by the transgenic females are also brown. The A3KMO silkworm lines express the transcript in the mid-gut, fat bodies, and Malpighian tubules. The KKMO line expresses the transcript only in the fat bodies and Malpighian tubules. The intensity of eye and egg color in the transgenic lines is proportional to the KMO expression level
physiological function
adaptive-and possibly regulatory-changes in mice with a targeted deletion of kynurenine 3-monooxygenase (Kmo-/-) are investigated kynurenine 3-monooxygenase-deficient mice are characterized using six behavioral assays relevant for the study of schizophrenia. Elimination of kynurenine 3-monooxygenase in mice is associated with multiple gene and functional alterations that appear to duplicate aspects of the psychopathology of several neuropsychiatric disorder
physiological function
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BcKMO is important for growth and development of Bortrytis cinerea. Enzyme BcKMO regulates the activities of cell wall degrading enzymes (CWDEs), toxins, and acid production
physiological function
KMO is a flavin-dependent hydroxylase that catalyzes the hydroxylation of L-kynurenine (L-Kyn) to 3-hydroxykynurenine (3-HK) in the kynurenine pathway (KP). The kynurenine pathway (KP) is the major mechanism for tryptophan catabolism with up to 99% of tryptophan being metabolized this way
physiological function
KMO is a flavin-dependent hydroxylase that catalyzes the hydroxylation of L-kynurenine (L-Kyn) to 3-hydroxykynurenine (3-HK) in the kynurenine pathway (KP). The kynurenine pathway (KP) is the major mechanism for tryptophan catabolism with up to 99% of tryptophan being metabolized this way
physiological function
KMO is a flavin-dependent hydroxylase that catalyzes the hydroxylation of L-kynurenine (L-Kyn) to 3-hydroxykynurenine (3-HK) in the kynurenine pathway (KP). The kynurenine pathway (KP) is the major mechanism for tryptophan catabolism with up to 99% of tryptophan being metabolized this way
physiological function
KMO is a flavin-dependent hydroxylase that catalyzes the hydroxylation of L-kynurenine (L-Kyn) to 3-hydroxykynurenine (3-HK) in the kynurenine pathway (KP). The kynurenine pathway (KP) is the major mechanism for tryptophan catabolism with up to 99% of tryptophan being metabolized this way. Numerous pathological conditions involve KP, including neurological disorders (e.g., schizophrenia, depression, and anxiety), autoimmune diseases (e.g., multiple sclerosis and rheumatoid arthritis), peripheral conditions (e.g. cardiovascular disease and acute pancreatitis), and neurodegenerative illnesses (e.g., Huntington's disease, Alzheimer's disease, and Parkinson's disease) and HIV
physiological function
kynurenine 3-monooxygenase (KMO) and kynureninase are reduced in ischemia-reperfusion procedure and further decreased in rejection allografts among mismatched pig KTx, molecular mechanism, overview. TEC injury in acutely rejection allografts is associated with alterations of Bcl2 family proteins, reduction of tight junction protein 1 (TJP1), and TEC-specific KMO. Three cytokines, IFNgamma, TNFalpha, and IL1beta, are identified as triggers of TEC injury by altering the expression of Bcl2, BID, and TJP1. Allograft rejection and TEC injury are always associated with a dramatic reduction of KMO. 3-Hydroxy-L-kynurenine (3HK) and hydroxyl-3 anthranilic acid (3HAA) as direct and downstream products of KMO, effectively protect TEC from injury via increasing expression of Bcl-xL and TJP1. 3HK and 3HAA effectively inhibit T cell proliferation
physiological function
kynurenine 3-monooxygenase (KMO) catalyzes the conversion of L-kynurenine to 3-hydroxykynurenine (3-HK) in the kynurenine pathway (KP), the major route of tryptophan degradation in eukaryotic organisms. Kynurenine 3-monooxygenase (KMO), a key player in the kynurenine pathway (KP) of tryptophan degradation, regulates the synthesis of the neuroactive metabolites 3-hydroxykynurenine (3-HK) and kynurenic acid (KYNA)
physiological function
kynurenine 3-monooxygenase (KMO) catalyzes the conversion of L-kynurenine to 3-hydroxykynurenine (3-HK) in the kynurenine pathway (KP), the major route of tryptophan degradation in eukaryotic organisms. Kynurenine 3-monooxygenase (KMO), a key player in the kynurenine pathway (KP) of tryptophan degradation, regulates the synthesis of the neuroactive metabolites 3-hydroxykynurenine (3-HK) and kynurenic acid (KYNA). KMO activity is implicated in several major brain diseases including Huntington's disease (HD) and schizophrenia in humans
physiological function
kynurenine 3-monooxygenase (KMO) is a mitochondrial protein involved in the eukaryotic tryptophan catabolic pathway and is linked to various diseases
physiological function
kynurenine 3-monooxygenase (KMO) is a mitochondrial protein involved in the eukaryotic tryptophan catabolic pathway and is linked to various diseases
physiological function
kynurenine 3-monooxygenase (KMO) regulates the levels of bioactive substances in the kynurenine pathway of tryptophan catabolism and its activity is tied to many diseases. The product of the enzyme reaction, 3-hydroxy-L-kynurenine (3-HK), is a neurotoxic agent that induces apoptosis and damages wide range of cell types. It is further converted to the free-radical generator 3-hydroxyanthranilate (3-HanA) which is then converted to the selective N-methyl-D-aspartate (NMDA) receptor agonist quinolinate
physiological function
kynurenine 3-monooxygenase (KMO) regulates the levels of bioactive substances in the kynurenine pathway of tryptophan catabolism and its activity is tied to many diseases. The product of the enzyme reaction, 3-hydroxy-L-kynurenine (3-HK), is a neurotoxic agent that induces apoptosis and damages wide range of cell types. It is further converted to the free-radical generator 3-hydroxyanthranilate (3-HanA) which is then converted to the selective N-methyl-D-aspartate (NMDA) receptor agonist quinolinate
physiological function
kynurenine 3-monooxygenase (KMO) regulates the levels of bioactive substances in the kynurenine pathway of tryptophan catabolism and its activity is tied to many diseases. The product of the enzyme reaction, 3-hydroxy-L-kynurenine (3-HK), is a neurotoxic agent that induces apoptosis and damages wide range of cell types. It is further converted to the free-radical generator 3-hydroxyanthranilate (3-HanA) which is then converted to the selective N-methyl-D-aspartate (NMDA) receptor agonist quinolinate. High levels of these substances correlate with the neurodegenerative diseases (Huntington's, Alzheimer's, and Parkinson's)
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
physiological function
kynurenine-3-monooxygenase (KMO) broadly inhibits viral infections via triggering NMDAR/Ca2+ influx and CaMKII/IRF3-mediated IFN-beta production. Kynurenine-3-monooxygenase (KMO), a key rate-limiting enzyme in the kynurenine pathway (KP), and quinolinic acid (QUIN), a key enzymatic product of KMO enzyme, exerts an antiviral function against a broad range of viruses. The enzymatic activity of KMO is required for its antiviral function, it is a key antiviral factor physiologically involved in modulating antiviral immunity. The supernatants from KMO-treated cells significantly inhibits HSV-1 infection in Vero cells and 293T cells. Mechanistically, QUIN induces the production of type I interferon (IFN-I) via activating the N-methyl-D-aspartate receptor (NMDAR) and Ca2+ influx to activate the calcium/calmodulin-dependent protein kinase II (CaMKII)/interferon regulatory factor 3 (IRF3). QUIN treatment effectively inhibits viral infections and alleviates disease progression in mice, detailed mechanism overview
physiological function
kynurenine-3-monooxygenase (KMO) is an enzyme that relies on nicotinamide adenine dinucleotide phosphate (NADP), a key site in the kynurenine pathway (KP), which has great effects on neurological diseases, cancer, and peripheral inflammation. Enzyme controlling the chief division of the KP, which directly controls downstream product quinolinic acid (QUIN) and indirectly controls kynurenic acid (KYNA), plays an important role in many diseases, especially neurological diseases. Role of KMO in different neurological diseases, such as Huntington's disease, schizophrenia, ischemic stroke and neuropathic headache, Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis, as well as in non-neurological diseases, such as acute pancreatitis and hepatocellular carcinoma, mechanisms, detailed overview
physiological function
renal tubular epithelial cells (TECs) are the primary targets of ischemia-reperfusion injury (IRI) and rejection by the recipient's immune response in kidney transplantation (KTx). Kynurenine 3-monooxygenase (KMO) and kynureninase are reduced in ischemia-reperfusion procedure, molecular mechanism, overview. TEC injury in acutely rejection allografts is associated with alterations of Bcl2 family proteins, reduction of tight junction protein 1 (TJP1), and TEC-specific KMO. Three cytokines, IFNgamma, TNFalpha, and IL1beta, aere identified as triggers of TEC injury by altering the expression of Bcl2, BID, and TJP1. Allograft rejection and TEC injury are always associated with a dramatic reduction of KMO. 3-Hydroxy-L-kynurenine (3HK) and hydroxyl-3 anthranilic acid (3HAA) as direct and downstream products of KMO, effectively protect TEC from injury via increasing expression of Bcl-xL and TJP1. 3HK and 3HAA effectively inhibit T cell proliferation
physiological function
role for kynurenine 3-monooxygenase in mitochondrial dynamics. KMO plays a role in the post-translational regulation of DRP1, mitochondrial role for KMO, independent from its enzymatic role in the kynurenine pathway (KP)
physiological function
the kynurenine pathway (KP) is the major route for tryptophan metabolism in mammals. Several metabolites in the KP, however, are potentially toxic, particularly 3-hydroxykynurenine (3-HK) and quinolinic acid (QA). QA is an excitotoxic agonist at the NMDA receptor, and 3-HK and QA are reported to increase in Huntington's disease (HD)
physiological function
viability of diffuse large B-cell lymphoma cells is regulated by kynurenine 3-monooxygenase activity
physiological function
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the kynurenine pathway (KP) is the major route for tryptophan metabolism in mammals. Several metabolites in the KP, however, are potentially toxic, particularly 3-hydroxykynurenine (3-HK) and quinolinic acid (QA). QA is an excitotoxic agonist at the NMDA receptor, and 3-HK and QA are reported to increase in Huntington's disease (HD)
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physiological function
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role for kynurenine 3-monooxygenase in mitochondrial dynamics. KMO plays a role in the post-translational regulation of DRP1, mitochondrial role for KMO, independent from its enzymatic role in the kynurenine pathway (KP)
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physiological function
Botrytis cinerea BC22
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BcKMO is important for growth and development of Bortrytis cinerea. Enzyme BcKMO regulates the activities of cell wall degrading enzymes (CWDEs), toxins, and acid production
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physiological function
Mus musculus C57BL/6N x C57BL/6J
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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
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the C-terminal region of pig liver KMO plays a dual role. First, it is required for the enzymatic activity. Second, it functions as a mitochondrial targeting signal
additional information
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the C-terminal region of pig liver KMO plays a dual role. First, it is required for the enzymatic activity. Second, it functions as a mitochondrial targeting signal
additional information
a Rossmann fold simply characterizes a secondary structure with an alternating motif of beta sheets and alpha helices, and is of importance because this domain non-covalently binds the FAD cofactor and also contains the active site of the enzyme for KMO
additional information
a Rossmann fold simply characterizes a secondary structure with an alternating motif of beta sheets and alpha helices, and is of importance because this domain non-covalently binds the FAD cofactor and also contains the active site of the enzyme for KMO
additional information
a Rossmann fold simply characterizes a secondary structure with an alternating motif of beta sheets and alpha helices, and is of importance because this domain non-covalently binds the FAD cofactor and also contains the active site of the enzyme for KMO
additional information
a Rossmann fold simply characterizes a secondary structure with an alternating motif of beta sheets and alpha helices, and is of importance because this domain non-covalently binds the FAD cofactor and also contains the active site of the enzyme for KMO
additional information
analysis of the extended ligand-binding pocket of in meso KMO and its binding mode
additional information
analysis of the extended ligand-binding pocket of in meso KMO and its binding mode
additional information
PfKMO is active without its membrane targeting domain, structure comparisons with the enzymes from Saccharomyces cerevisiae and Homo sapiens, overview
additional information
residues Tyr 99, Tyr 194, and Glu 366 are critical to the enzymatic activity of KMO
additional information
ScKMO is active without its membrane targeting domain, structure comparisons with the enzymes from Homo sapiens (hKMO) and Pseudomonas fluorescens (pfKMO), overview
additional information
structure comparisons with the enzymes from Saccharomyces cerevisiae (scKMO) and Pseudomonas fluorescens (pfKMO), overview
additional information
the structure reveals that the aniline moiety of L-Kyn is stacked roughly perpendicular to the isoalloxazine of the FAD and that the C3 of the substrate is within 4.6 A of the flavin C4a position
additional information
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the structure reveals that the aniline moiety of L-Kyn is stacked roughly perpendicular to the isoalloxazine of the FAD and that the C3 of the substrate is within 4.6 A of the flavin C4a position