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Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
5-bromo-L-kynurenine + NADPH + H+ + O2
5-bromo-3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
5-chloro-L-kynurenine + NADPH + H+ + O2
5-chloro-3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
L-kynurenine + NADH + H+ + O2
3-hydroxy-L-kynurenine + NAD+ + H2O
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
L-kynurenine + NADPH + O2
? + NADP+
o-hydroxybenzoyl-DL-alanine + NADPH + O2
? + NADP+
additional information
?
-
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
-
-
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
-
-
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
-
enzyme inhibition in immature rats shifts cerebral kynurenine pathway metabolism toward increased kynurenic acid formation, overview
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
-
-
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
-
the enzyme is involved in the kynurenine pathway of tryptophan metabolsim, overview
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
-
the reaction is central to the tryptophan degradative pathway, overview, and takes place within microglial cells defining cellular concentrations of the N-methyl-D-aspatate receptor agonist quinolinate and antagonist kynurenate
the product acts as apoptotic signal
-
ir
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
-
enzyme activity depends on the reduction state of the enzyme
-
-
ir
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
-
the reaction is central to the tryptophan degradative pathway, overview, and takes place within microglial cells defining cellular concentrations of the N-methyl-D-aspatate receptor agonist quinolinate and antagonist kynurenate
the product acts as apoptotic signal
-
ir
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
-
enzyme activity depends on the reduction state of the enzyme
-
-
ir
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
-
-
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
-
enzyme inhibition in immature rats shifts cerebral kynurenine pathway metabolism toward increased kynurenic acid formation, overview
-
-
?
L-kynurenine + NADH + H+ + O2
3-hydroxy-L-kynurenine + NAD+ + H2O
-
-
-
?
L-kynurenine + NADH + H+ + O2
3-hydroxy-L-kynurenine + NAD+ + H2O
-
-
-
?
L-kynurenine + NADH + H+ + O2
3-hydroxy-L-kynurenine + NAD+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
the enzyme is involved in tryptophan catabolism
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in Parkinsonian monkeys, enzyme regulation and involvement in Parkinson's disease, overview
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
Mus musculus C57BL/6N x C57BL/6J
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
enzyme has a key role in L-tryptophan catabolism and in synthesis of ommochrome pigments in the eyes of the mosquitos
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
enzyme has a key role in L-tryptophan catabolism and in synthesis of ommochrome pigments in the eyes of the mosquitos
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
the enzyme is not involved in regulation of 3-hydroxy-L-kynurenine level in vivo
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
enzyme is involved in L-tryptophan catabolism, pathway regulation in comparison to other species, overview
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
function of the enzyme may change from a role in immunosuppression at the maternal-fetal interface in early pregnancy to one associated with regulation of fetoplacental blood flow or placental metabolism in late gestation
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
step in L-tryptophan catabolism, overview
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
enzyme is involved in L-tryptophan catabolism, pathway regulation in comparison to other species, overview
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
enzyme is involved in L-tryptophan catabolism, pathway regulation in comparison to other species, overview
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
binding of L-kynurenine to the oxidized enzyme is relatively slow and involves at least two reversible steps
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
r
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
no reaction with D-isomer
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
enzyme is involved in L-tryptophan catabolism, pathway regulation in comparison to other species, overview
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
no reaction with D-isomer
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
NADH is less effective
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
step in L-tryptophan catabolism, overview
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + O2
? + NADP+
-
increased activity in injured brain regions following cerebral ischemia
-
-
?
L-kynurenine + NADPH + O2
? + NADP+
-
-
-
-
?
L-kynurenine + NADPH + O2
? + NADP+
-
increased activity in the spinal cord with experimental allergic encephalopathy
-
-
?
L-kynurenine + NADPH + O2
? + NADP+
-
key enzyme in the kynurenine pathway of tryptophan degradation
-
-
?
L-kynurenine + NADPH + O2
? + NADP+
-
-
-
-
?
L-kynurenine + NADPH + O2
? + NADP+
-
rate limiting step in the pyridine nucleotide biosynthesis from tryptophan
-
-
?
o-hydroxybenzoyl-DL-alanine + NADPH + O2
? + NADP+
-
about 25% of the activity with L-kynurenine
-
-
?
o-hydroxybenzoyl-DL-alanine + NADPH + O2
? + NADP+
-
about 25% of the activity with L-kynurenine
-
-
?
additional information
?
-
enzyme is involved in eye pigmentation
-
-
?
additional information
?
-
-
the enzyme is a very potent suppressor of toxicity of a fragment of the protein huntingtin, Htt, which causes the neurodegenerative Huntington disease by aggregation in nuclear and cytoplasmic inclusion bodies
-
-
?
additional information
?
-
following binding of L-KYN to KMO, NADPH acts as an electron donor and reduces FAD, leading to the formation of a L-KYN-FAD-hydroperoxide intermediate. L-KYN is then oxidised, resulting in the release of 3-HK and water
-
-
-
additional information
?
-
the mechanism of L-Kyn catalysis by KMO is composed of reductive and oxidative half reactions. The binding of the substrate induces the reduction of FAD by NADH or by NADPH. The initiation of FAD reduction is not unique to the substrate binding. It is also observed upon the binding of several inhibitors. The molecules that induce reduction of FAD other than the substrate are named as non-substrate effectors. Since the non-substrate effectors eliminate the hydroxyl transfer event but nonetheless initiate the formation of the FAD-hydroperoxide intermediate, they cause hydrogen peroxide formation. The triggering factor can arise from the substrate induced conformational changes in the loop above the isoalloxazine ring system
-
-
-
additional information
?
-
-
the kynurenine pathway of tryptophan degradation contains three neuroactive metabolites: the neuroinhibitory agent kynurenic acid and, in a competing branch, the free radical generator 3-hydroxykynurenine and the excitotoxin quinolinic acid, newborn mice delivered by UPF 648-treated mothers and immediately exposed to neonatal asphyxia show further enhanced brain kynurenic acid levels, overview
-
-
?
additional information
?
-
a coupled assay with glucose 6-phosphate and GAPDH is used
-
-
-
additional information
?
-
following binding of L-KYN to KMO, NADPH acts as an electron donor and reduces FAD, leading to the formation of a L-KYN-FAD-hydroperoxide intermediate. L-KYN is then oxidised, resulting in the release of 3-HK and water
-
-
-
additional information
?
-
density functional theory (DFT) calculations in the absence and in the presence of the kynurenine 3-monooxygenase (KMO) enzyme, crystal structure (PDB ID 5NAK)-based calculations involved a quantum cluster model in which the active site of the enzyme with the substrate L-Kyn is represented with 348 atoms. According to the deduced mechanism, KMO-catalyzed hydroxylation reaction takes place with four transformations. In the initial transition state, FAD delivers its peroxy hydroxyl to the L-Kyn ring, creating an sp3-hybridized carbon center. Then, the hydrogen on the hydroxyl moiety is immediately transferred back to the proximal oxygen that remains on FAD. These consequent transformations are in line with the somersault rearrangement previously described for similar enzymatic systems. The second step corresponds to a hydride shift from the sp3-hybridized carbon of the substrate ring to its adjacent carbon, producing the keto form of 3-HK. Then, keto-3-HK is transformed into its enol form (3-HK) with a water-assisted tautomerization. Lastly, FAD is oxidized with a water-assisted dehydration, which also involves 3-HK as a catalyst. Residues Asn54, Pro318, and a crystal water molecule are seen to play significant roles in the proton relays
-
-
-
additional information
?
-
the mechanism of L-Kyn catalysis by KMO is composed of reductive and oxidative half reactions. The binding of the substrate induces the reduction of FAD by NADH or by NADPH. The initiation of FAD reduction is not unique to the substrate binding. It is also observed upon the binding of several inhibitors. The molecules that induce reduction of FAD other than the substrate are named as non-substrate effectors, e.g. GSK180 and Ro 61-8048 for enzyme pfKMO. Since the non-substrate effectors eliminate the hydroxyl transfer event but nonetheless initiate the formation of the FAD-hydroperoxide intermediate, they cause hydrogen peroxide formation. The triggering factor can arise from the substrate induced conformational changes in the loop above the isoalloxazine ring system
-
-
-
additional information
?
-
-
catalyzes NADH- and NADPH-linked reductions of low molecular weight acceptors such as 2,6-dichlorophenolindophenol and ferricyanide
-
-
?
additional information
?
-
-
age affects the enzyme activities of tryptophan metabolism along the kynurenine pathway, one of the various tryptophan metabolic routes, kynurenine 3-monooxygenase activity progressively decreases with age in liver and kidney of newborn to mature rats, quantitative overview
-
-
?
additional information
?
-
-
the kynurenine pathway of tryptophan degradation contains three neuroactive metabolites: the neuroinhibitory agent kynurenic acid and, in a competing branch, the free radical generator 3-hydroxykynurenine and the excitotoxin quinolinic acid, rat pups delivered by UPF 648-treated mothers and immediately exposed to neonatal asphyxia show further enhanced brain kynurenic acid levels, overview
-
-
?
additional information
?
-
-
the enzyme is responsible for driving formation of neurotoxic and neuroprotective kynurenine metabolites, regulation mechanism, overview
-
-
?
additional information
?
-
following binding of L-KYN to KMO, NADPH acts as an electron donor and reduces FAD, leading to the formation of a L-KYN-FAD-hydroperoxide intermediate. L-KYN is then oxidised, resulting in the release of 3-HK and water
-
-
-
additional information
?
-
-
the enzyme is a very potent suppressor of toxicity of a fragment of the protein huntingtin, Htt, which causes the neurodegenerative Huntington disease in humans by aggregation in nuclear and cytoplasmic inclusion bodies
-
-
?
additional information
?
-
the mechanism of L-Kyn catalysis by KMO is composed of reductive and oxidative half reactions. The binding of the substrate induces the reduction of FAD by NADH or by NADPH. The initiation of FAD reduction is not unique to the substrate binding. It is also observed upon the binding of several inhibitors. The molecules that induce reduction of FAD other than the substrate are named as non-substrate effectors, e.g. UPF-648 for enzyme scKMO. Since the non-substrate effectors eliminate the hydroxyl transfer event but nonetheless initiate the formation of the FAD-hydroperoxide intermediate, they cause hydrogen peroxide formation. The triggering factor can arise from the substrate induced conformational changes in the loop above the isoalloxazine ring system
-
-
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
L-kynurenine + NADH + H+ + O2
3-hydroxy-L-kynurenine + NAD+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
L-kynurenine + NADPH + O2
? + NADP+
additional information
?
-
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
-
enzyme inhibition in immature rats shifts cerebral kynurenine pathway metabolism toward increased kynurenic acid formation, overview
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
-
the enzyme is involved in the kynurenine pathway of tryptophan metabolsim, overview
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
-
the reaction is central to the tryptophan degradative pathway, overview, and takes place within microglial cells defining cellular concentrations of the N-methyl-D-aspatate receptor agonist quinolinate and antagonist kynurenate
the product acts as apoptotic signal
-
ir
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
-
the reaction is central to the tryptophan degradative pathway, overview, and takes place within microglial cells defining cellular concentrations of the N-methyl-D-aspatate receptor agonist quinolinate and antagonist kynurenate
the product acts as apoptotic signal
-
ir
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
-
-
-
-
?
kynurenine + NADPH + O2
3-hydroxy-kynurenine + NADP+ + H2O
-
enzyme inhibition in immature rats shifts cerebral kynurenine pathway metabolism toward increased kynurenic acid formation, overview
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
the enzyme is involved in tryptophan catabolism
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in Parkinsonian monkeys, enzyme regulation and involvement in Parkinson's disease, overview
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
Mus musculus C57BL/6N x C57BL/6J
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
?
L-kynurenine + NADPH + H+ + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
-
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
enzyme has a key role in L-tryptophan catabolism and in synthesis of ommochrome pigments in the eyes of the mosquitos
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
enzyme has a key role in L-tryptophan catabolism and in synthesis of ommochrome pigments in the eyes of the mosquitos
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
the enzyme is not involved in regulation of 3-hydroxy-L-kynurenine level in vivo
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
enzyme is involved in L-tryptophan catabolism, pathway regulation in comparison to other species, overview
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
function of the enzyme may change from a role in immunosuppression at the maternal-fetal interface in early pregnancy to one associated with regulation of fetoplacental blood flow or placental metabolism in late gestation
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
step in L-tryptophan catabolism, overview
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
enzyme is involved in L-tryptophan catabolism, pathway regulation in comparison to other species, overview
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
enzyme is involved in L-tryptophan catabolism, pathway regulation in comparison to other species, overview
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
enzyme is involved in L-tryptophan catabolism, pathway regulation in comparison to other species, overview
-
-
?
L-kynurenine + NADPH + O2
3-hydroxy-L-kynurenine + NADP+ + H2O
-
step in L-tryptophan catabolism, overview
-
-
?
L-kynurenine + NADPH + O2
? + NADP+
-
increased activity in injured brain regions following cerebral ischemia
-
-
?
L-kynurenine + NADPH + O2
? + NADP+
-
-
-
-
?
L-kynurenine + NADPH + O2
? + NADP+
-
increased activity in the spinal cord with experimental allergic encephalopathy
-
-
?
L-kynurenine + NADPH + O2
? + NADP+
-
key enzyme in the kynurenine pathway of tryptophan degradation
-
-
?
L-kynurenine + NADPH + O2
? + NADP+
-
-
-
-
?
L-kynurenine + NADPH + O2
? + NADP+
-
rate limiting step in the pyridine nucleotide biosynthesis from tryptophan
-
-
?
additional information
?
-
enzyme is involved in eye pigmentation
-
-
?
additional information
?
-
-
the enzyme is a very potent suppressor of toxicity of a fragment of the protein huntingtin, Htt, which causes the neurodegenerative Huntington disease by aggregation in nuclear and cytoplasmic inclusion bodies
-
-
?
additional information
?
-
-
the kynurenine pathway of tryptophan degradation contains three neuroactive metabolites: the neuroinhibitory agent kynurenic acid and, in a competing branch, the free radical generator 3-hydroxykynurenine and the excitotoxin quinolinic acid, newborn mice delivered by UPF 648-treated mothers and immediately exposed to neonatal asphyxia show further enhanced brain kynurenic acid levels, overview
-
-
?
additional information
?
-
-
age affects the enzyme activities of tryptophan metabolism along the kynurenine pathway, one of the various tryptophan metabolic routes, kynurenine 3-monooxygenase activity progressively decreases with age in liver and kidney of newborn to mature rats, quantitative overview
-
-
?
additional information
?
-
-
the kynurenine pathway of tryptophan degradation contains three neuroactive metabolites: the neuroinhibitory agent kynurenic acid and, in a competing branch, the free radical generator 3-hydroxykynurenine and the excitotoxin quinolinic acid, rat pups delivered by UPF 648-treated mothers and immediately exposed to neonatal asphyxia show further enhanced brain kynurenic acid levels, overview
-
-
?
additional information
?
-
-
the enzyme is responsible for driving formation of neurotoxic and neuroprotective kynurenine metabolites, regulation mechanism, overview
-
-
?
additional information
?
-
-
the enzyme is a very potent suppressor of toxicity of a fragment of the protein huntingtin, Htt, which causes the neurodegenerative Huntington disease in humans by aggregation in nuclear and cytoplasmic inclusion bodies
-
-
?
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(1S,2S)-2-(3,4-dichlorobenzoyl)-cyclopropane-1-carboxylic acid
-
KMO inhibitor UPF 648, totally blocks KMO at 0.1 and 0.01 mM and is still highly active at 0.001 mM (81% inhibition). It reduces 3-hydroxykynurenine synthesis by 64% without affecting kynurenic acid formation. In neuron-depleted striata, UPF 648 decreases both 3-hydroxykynurenine and quinolinic acid production by 77% and 66%, respectively and also raises kynurenic acid synthesis by 27%. 0.1 mM UPF 648 blocks KMO in both lesioned and contralateral striatum, but does not interfere with KAT activity in either tissue
(6-chloro-1H-indazol-1-yl)acetic acid
-
(6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid
-
(R)-3-(5-chloro-2-oxo-6-(1-(pyridin-2-yl)ethoxy)benzo[d]oxazol-3(2H)-yl)propanoate
-
(R,S)-2-amino-oxo-4-(3',4'-dichlorophenyl)butanoic acid
-
FCE 28833, 50% inhibition at 0.2 microM, blocks not only the cerebral but also the peripheral enzyme
(R,S)-2-amino-oxo-4-(3'-4'-dichlorophenyl)butanoic acid
-
-
(S)-3-(5-Chloro-2-oxo-6-(1-(pyridin-2-yl)ethoxy)benzo[d]oxazol-3(2H)-yl)propanoate
-
(S)-9-(4-aminopiperazine-1-yl)-8-fluoro-3-methyl-6-oxo-2,3,5,6-tetrahydro-4H-1-oxa-3a-azaphenalene-5-carboxylic acid
-
does not affect KMO activity significantly, 1 mM inhibits by 17%
1-cyclopentyl-N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)methanesulfonamide
-
-
2,2,2-trifluoro-N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)ethane-1-sulfonamide
-
-
2-(3,4-dichlorobenzoyl)-cyclopropane-1-carboxylic acid
-
2-(3,4-dichlorobenzoyl)cyclopropane-1-carboxylic acid
-
2-(benzyloxy)-5-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
-
2-amino-3-(6-chloro-1H-indazol-1-yl)propanoic acid
-
2-benzyl-4-(3,4-dichlorophenyl)-4-oxo-butanoic acid
-
-
2-hydroxy-4-(3,4-dichlorophenyl)-4-oxobutanoic acid
-
-
2-oxo acid derivatives
-
of the 3 branched chain amino acids
2-oxoglutarate
-
mixed type inhibitor
3,4-dichlorobenzoyl alanine
3,4-CBA or FCE 28833, a substrate analogue
-
3,4-dichlorohippuric acid
-
3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
-
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
3,4-dimethoxy-N-[5-(3-nitrophenyl)-4-[(piperidin-1-yl)methyl]-1,3-thiazol-2-yl]benzene-1-sulfonamide
-
3,4-dimethoxyhippuric acid
3,5-dibromo-L-kynurenine
potent competitive inhibitor
3-(1H-indazol-1-yl)propanoic acid
-
3-(4-methyl-5-phenyl-1H-pyrazol-1-yl)benzoic acid
-
3-(5,6-dichloro-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
-
3-(5,6-dichloro-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)-propanoic acid
-
3-(5-chloro-1,2-benzoxazol-3-yl)propanoic acid
-
3-(5-chloro-1H-indazol-1-yl)propanoic acid
-
3-(5-chloro-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
-
3-(5-chloro-6-cyano-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
-
3-(5-chloro-6-cyclopropoxy-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)propanoic acid
-
3-(5-chloro-6-ethoxy-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
-
3-(5-chloro-6-ethoxy-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)propanoic acid
-
3-(5-chloro-6-ethyl-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
-
3-(5-chloro-6-ethyl-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)propanoic acid
-
3-(5-chloro-6-methoxy-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
-
3-(5-chloro-6-methoxy-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)-propanoic acid
-
3-(5-chloro-6-methyl-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
-
3-(5-chloro-6-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)propanoic acid
-
3-(5-chloro-6-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl)propanoic acid
-
3-(5-chloro-7-methyl-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
-
3-(5-cyano-2-methylidene-1,3-benzoxazol-3(2H)-yl)propanoic acid
-
3-(5-methoxy-2-methylidene-1,3-benzoxazol-3(2H)-yl)propanoic acid
-
3-(6-bromo-1H-indazol-1-yl)propanoic acid
-
3-(6-chloro-1H-benzotriazol-1-yl)propanoic acid
-
3-(6-chloro-1H-indazol-1-yl)-2-hydroxypropanoic acid
-
3-(6-chloro-1H-indazol-1-yl)-2-methylpropanoic acid
-
3-(6-chloro-1H-indazol-1-yl)butanoic acid
-
3-(6-chloro-1H-indazol-1-yl)propanoic acid
-
3-(6-chloro-1H-indol-1-yl)propanoic acid
-
3-(6-chloro-3-methyl-1H-indazol-1-yl)propanoic acid
-
3-(6-chloro-3-oxo-3,4-dihydro-2H-1-benzopyran-4-yl)propanoic acid
-
3-(6-methyl-1H-indazol-1-yl)propanoic acid
-
3-(dimethylamino)-N-(6-[2-(pyrrolidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
-
3-nitrobenzoylalanine
-
-
3-[2-methylidene-5-(trifluoromethyl)-1,3-benzoxazol-3(2H)-yl]propanoic acid
-
3-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
-
3-[5-chloro-2-oxo-6-(propan-2-yl)-1,3-benzoxazol-3(2H)-yl]propanoic acid
-
3-[5-chloro-2-oxo-6-(pyridin-2-ylmethoxy)-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
-
3-[5-chloro-2-oxo-6-(trifluoromethyl)-1,3-benzoxazol-3(2H)-yl]propanoic acid
-
3-[5-chloro-2-oxo-6-[(1R)-1-(pyridazin-3-yl)ethoxy]-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
-
3-[5-chloro-2-oxo-6-[(1R)-1-(pyridin-2-yl)ethoxy]-2,3-dihydro-1,3-benzothiazol-3-yl]propanoic acid
-
3-[5-chloro-2-oxo-6-[(1R)-1-(pyrimidin-2-yl)ethoxy]-2,3-dihydro-1,3-benzoxazol-3-yl]-propanoic acid
-
3-[5-chloro-2-oxo-6-[(propan-2-yl)oxy]-1,3-benzoxazol-3(2H)-yl]propanoic acid
-
3-[5-chloro-2-oxo-6-[1-(pyridin-2-yl)ethoxy]-2,3-dihydro-1,3-benzoxazol-3-yl]-propanoic acid
-
3-[5-chloro-2-oxo-6-[2-(pyrrolidin-1-yl)ethoxy]-2,3-dihydro-1,3-benzoxazol-3-yl]-propanoic acid
-
3-[5-chloro-6-(2-methoxyethoxy)-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
-
3-[5-chloro-6-(2-methylpropyl)-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
-
3-[5-chloro-6-(cyclobutylmethoxy)-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
-
3-[5-chloro-6-(cyclopropylmethoxy)-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]-propanoic acid
-
3-[5-chloro-6-(cyclopropyloxy)-2-oxo-1,3-benzoxazol-3(2H)-yl]propanoic acid
-
3-[5-chloro-6-[(1R)-1-(1,3-oxazol-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
-
3-[5-chloro-6-[(1R)-1-(4-methylpyridin-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
-
3-[5-chloro-6-[(1R)-1-(5-chloropyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl]-propanoic acid
-
3-[5-chloro-6-[(1R)-1-(5-chloropyridin-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
-
3-[5-chloro-6-[(1R)-1-(5-fluoropyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl]propanoic acid
-
3-[5-chloro-6-[(1R)-1-(5-fluoropyridin-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
-
3-[5-chloro-6-[(1R)-1-(5-methylpyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl]-propanoic acid
-
3-[5-chloro-6-[(1R)-1-(5-methylpyridin-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
-
3-[5-chloro-6-[(1R)-1-(6-methylpyridazin-3-yl)ethoxy]-1,2-benzoxazol-3-yl]propanoic acid
-
3-[5-chloro-6-[(1R)-1-(6-methylpyridin-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
-
3-[5-chloro-6-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl]propanoic acid
-
3-[6-(benzyloxy)-5-chloro-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
-
3-[6-chloro-3-oxo-7-[(1R)-1-(pyridin-2-yl)ethoxy]-3,4-dihydro-2H-1,4-benzoxazin-4-yl]propanoic acid
-
3-[6-chloro-5-[(1R)-1-(pyridin-2-yl)ethoxy]-1H-indazol-1-yl]propanoic acid
-
3-[6-chloro-5-[(1R)-1-(pyridin-2-yl)ethoxy]-1H-indol-1-yl]-propanoic acid
-
4-(3,4-dichlorophenyl)-4-oxobutanoic acid
-
desamino FCE 28833
4-(6-chloro-1H-indazol-1-yl)butanoic acid
-
4-amino-N-[4-(2-fluoro-5-trifluoromethyl-phenyl)-thiazol-2-yl]-benzenesulfonamide
-
-
4-amino-N-[4-[2-fluoro-5-(trifluoromethyl)phenyl]thiazol-2-yl]benzenesulfonamide
-
50% inhibition at 19nM
4-chloro-2-([5-chloro-2-(5-methoxy-1,3-dihydro-2H-isoindol-2-yl)-1,3-thiazole-4-carbonyl](methyl)amino)-5-fluorobenzoic acid
-
4-methyl-N-(6-[2-(4-methylpiperazin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
-
4-methyl-N-(6-[2-(morpholin-4-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
-
4-methyl-N-(6-[2-(piperidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
4-methyl-N-(6-[2-(pyrrolidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
-
4-methyl-N-[6-(1-methyl-1H-indol-7-yl)pyridazin-3-yl]benzene-1-sulfonamide
-
-
4-methyl-N-[6-(1-methyl-2,3-dihydro-1H-indol-7-yl)pyridazin-3-yl]benzene-1-sulfonamide
-
-
4-methyl-N-[6-(quinolin-8-yl)pyridazin-3-yl]benzene-1-sulfonamide
-
-
5-bromo-3-chloro-DL-kynurenine
-
5-bromo-3-methyl-DL-kynurenine
-
6-[3-(4-chloro-3-fluorophenyl)pyridin-2-yl]-1-methylquinazoline-2,4(1H,3H)-dione
-
6-[4-chloro-3-(cyclopropyloxy)phenyl]pyrimidine-4-carboxylic acid
-
7-chloro-3-methyl-1H-pyrrolo[3,2-c]quinoline-4-carboxylic acid
-
relatively potent and selective inhibitor
alpha-Ketoisocaproate
-
non competitive inhibition
anthranilic acid
-
22% inhibition at 2 mM and 11% inhibition at 0.2 mM
benzoylalanine
-
KMO inhibitor that mimics the substrate structure, and also stimulates reduction of the flavin by NADPH
chloride
mixed-type inhibition
EDTA
-
68% inhibition at 2 mM
ethyl (6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetate
-
ianthellamide A
an octopamine derivative isolated from the Australian marine sponge Ianthella quadrangulata, selectively inhibits KMO
-
Kynurenic acid
-
13% inhibition at 2 mM and 5% inhibition at 0.2 mM
L-tryptophan
-
35% inhibition at 2 mM and 22% inhibition at 0.2 mM
m-nitrobenzoylalanine
-
KMO inhibitor that mimics the substrate structure, and also stimulates reduction of the flavin by NADPH
N-(6-(5-fluoro-2-(piperidin-1-yl)phenyl)pyridazin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)methanesulfonamide
-
N-(6-[2-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
-
N-(6-[2-fluoro-6-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
-
N-(6-[3-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
-
N-(6-[3-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
-
N-(6-[4-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxan-2-yl)methanesulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxan-3-yl)methanesulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxan-4-yl)methanesulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxolan-2-yl)methanesulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-2-methoxyethane-1-sulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-3-methoxypropane-1-sulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)butane-2-sulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)ethanesulfonamide
-
-
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)propane-1-sulfonamide
-
-
N-(6-[5-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
-
-
N-[6-(2-ethylphenyl)pyridazin-3-yl]-4-methylbenzene-1-sulfonamide
-
-
N-[6-(2-methoxyphenyl)pyridazin-3-yl]-4-methylbenzene-1-sulfonamide
-
-
N-[6-(3-chlorophenyl)pyridazin-3-yl]-2-(dimethylamino)benzene-1-sulfonamide
-
-
N-[6-(3-chlorophenyl)pyridazin-3-yl]-3-(dimethylamino)benzene-1-sulfonamide
-
-
N-[6-(3-chlorophenyl)pyridazin-3-yl]-3-methylbenzene-1-sulfonamide
-
-
N-[6-(3-chlorophenyl)pyridazin-3-yl]-4-(dimethylamino)benzene-1-sulfonamide
-
-
N-[6-(3-chlorophenyl)pyridazin-3-yl]pyridine-2-sulfonamide
-
-
N-[6-(3-chlorophenyl)pyridazin-3-yl]pyridine-3-sulfonamide
-
-
N-[6-(isoquinolin-8-yl)pyridazin-3-yl]-4-methylbenzene-1-sulfonamide
-
-
p-chloromercuribenzoate
-
weak, 50% inhibition at 0.4 M
pyridoxal
-
less potent than pyridoxal phosphate
pyruvate
-
mixed type inhibitor
xanthurenic acid
-
48% inhibition at 2 mM and 13% inhibition at 0.2 mM
(6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid
KMO-inhibitor 1
-
(6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid
KMO-inhibitor 1
-
(6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid
KMO-inhibitor 1
-
(6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid
-
-
(6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid
KMO-inhibitor 1
-
(m-nitrobenzoyl)-alanine
-
mNBA, leads to an increase of L-kynurenine and kynurenic acid concentrations in the brain cortex after application in vivo
(m-nitrobenzoyl)-alanine
-
mNBA, leads to an increase of L-kynurenine and kynurenic acid concentrations in the brain cortex after application in vivo
(m-nitrobenzoyl)-alanine
-
various pyrrolo[3,2-c]quinoline derivates cause enzyme inhibition
(m-nitrobenzoyl)-alanine
-
50% inhibition at 0.9 micromolar
2-(3,4-dichlorobenzoyl)-cyclopropane-1-carboxylic acid
UPF648, UPF648 prevents the binding of the native substrate KYN by binding closely to the FAD cofactor. In a transgenic Drosophila melanogaster model of Huntington's disease, UPF648 is shown to mitigate disease-relevant phenotypes. While UPF648 inhibits KMO, it also significantly increases the production of hydrogen peroxide by almost 20fold
-
2-(3,4-dichlorobenzoyl)-cyclopropane-1-carboxylic acid
UPF648, UPF648 prevents the binding of the native substrate KYN by binding closely to the FAD cofactor. Enzyme-binding structure determination (PDB ID 4J36) and further pharmacophore modeling
-
2-(3,4-dichlorobenzoyl)cyclopropane-1-carboxylic acid
-
-
2-(3,4-dichlorobenzoyl)cyclopropane-1-carboxylic acid
PNU-168754
-
2-(benzyloxy)-5-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
-
-
2-(benzyloxy)-5-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
R380, a residue from the enzyme's C-terminal region, forms hydrogen bonds with the carboxylic acid moiety of the inhibitor, residues R85, Y99 and Y398 also form bonds to 2-(benzyloxy)-5-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
-
3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Ro 61-8048
-
3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Ro 61-8048
-
3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Ro 61-8048
-
3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Ro-61-8048
-
3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Ro 61-8048, different binding modes of the inhibitor Ro 61-8048 in scKMO and in pfKMO, overview
-
3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Ro 61-8048
-
3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Ro 61-8048, different binding modes of the inhibitor Ro 61-8048 in scKMO and in pfKMO, overview. Ro 61-8048-scKMO complex structure analysis
-
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
Ro-61-8048, shows a greater potency than the previously discussed native substrate analogue 3,4-dichlorobenzoyl alanine
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
-
leads to an increase of L-kynurenine and kynurenic acid concentrations in the brain cortex after application in vivo
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
-
Ro-61-8048, 50% inhibition at 37 nM
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
-
leads to an increase of L-kynurenine and kynurenic acid concentrations in the brain cortex after application in vivo
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
-
inhibition after oral or intraperitoneal administration
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
-
i.e. Ro 61-8048, high-affinity low molecular inhibitor
3,4-dimethoxy-N-[5-(3-nitrophenyl)-4-[(piperidin-1-yl)methyl]-1,3-thiazol-2-yl]benzene-1-sulfonamide
JM-6
-
3,4-dimethoxy-N-[5-(3-nitrophenyl)-4-[(piperidin-1-yl)methyl]-1,3-thiazol-2-yl]benzene-1-sulfonamide
JM-6
-
3,4-dimethoxyhippuric acid
-
3,4-dimethoxyhippuric acid
-
3-(4-methyl-5-phenyl-1H-pyrazol-1-yl)benzoic acid
-
-
3-(4-methyl-5-phenyl-1H-pyrazol-1-yl)benzoic acid
-
-
3-(5-chloro-6-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl)propanoic acid
GSK-065
-
3-(5-chloro-6-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl)propanoic acid
GSK-065
-
3-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
-
-
3-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
-
-
4-chloro-2-([5-chloro-2-(5-methoxy-1,3-dihydro-2H-isoindol-2-yl)-1,3-thiazole-4-carbonyl](methyl)amino)-5-fluorobenzoic acid
-
-
4-chloro-2-([5-chloro-2-(5-methoxy-1,3-dihydro-2H-isoindol-2-yl)-1,3-thiazole-4-carbonyl](methyl)amino)-5-fluorobenzoic acid
ligand-binding structure, overview
-
4-methyl-N-(6-[2-(piperidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
permeable and strong KMO inhibitor
-
4-methyl-N-(6-[2-(piperidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
-
6-[3-(4-chloro-3-fluorophenyl)pyridin-2-yl]-1-methylquinazoline-2,4(1H,3H)-dione
-
-
6-[3-(4-chloro-3-fluorophenyl)pyridin-2-yl]-1-methylquinazoline-2,4(1H,3H)-dione
-
-
6-[4-chloro-3-(cyclopropyloxy)phenyl]pyrimidine-4-carboxylic acid
CHDI-340246
-
6-[4-chloro-3-(cyclopropyloxy)phenyl]pyrimidine-4-carboxylic acid
CHDI-340246
-
CHDI-340246
-
-
CHDI-340246
CHDI-340246-scKMO complex structure analysis
-
Cl-
low concentrations of NaCl solution stabilize the enzyme and decrease the limiting rate of reduction by 30fold. This effect is specific to the Cl- anion. The rate of hydroxylation is also moderately reduced with the introduction of NaCl solution
Cl-
-
70% inhibition with 0.1 M NaCl or KCl, competitive with respect to NADPH and non-competitive with respect to L-kynurenine
CN-
-
high concentration
CN-
-
inhibition at 0.01 M
ethyl (6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetate
KMO-inhibitor 1b, in the ligand structure, the carboxylate group of the inhibitor sits close to residues R83/Y97/N368 in the KMO active site. Several interactions between ligand and protein have been identified
-
ethyl (6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetate
KMO-inhibitor 1b, in the ligand structure, the carboxylate group of the inhibitor sits close to residues R83/Y97/N368 in the KMO active site. Several interactions between ligand and protein have been identified
-
ethyl (6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetate
KMO-inhibitor 1b, in the ligand structure, the carboxylate group of the inhibitor sits close to residues R83/Y97/N368 in the KMO active site. Several interactions between ligand and protein have been identified
-
GSK065
suitable for preclinical evaluation
GSK065
suitable for preclinical evaluation
GSK366
suitable for preclinical evaluation
GSK366
suitable for preclinical evaluation
GSK428
-
GSK775
-
GSK891
-
N-(6-(5-fluoro-2-(piperidin-1-yl)phenyl)pyridazin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)methanesulfonamide
a brain-permeable and metabolically stable kynurenine monooxygenase inhibitor. The compound exhibits high brain permeability and a long-lasting pharmacokinetics profile in monkeys. Enzyme inhibition leads to production of neuroprotective kynurenic acid in the brain
-
N-(6-(5-fluoro-2-(piperidin-1-yl)phenyl)pyridazin-3-yl)-1-(tetrahydro-2H-pyran-4-yl)methanesulfonamide
a brain-permeable and metabolically stable kynurenine monooxygenase inhibitor. The compound exhibits high brain permeability and a long-lasting pharmacokinetics profile in monkeys, and neuroprotective kynurenic acid is increased by a single administration of the inhibitor in R6/2 mouse brain
-
pyridoxal 5'-phosphate
noncompetitive
pyridoxal 5'-phosphate
-
non competitive inhibition
Ro 61-8048
-
high-affinity low molecular inhibitor
Ro 61-8048
noncompetitive. Theinhibitor is bound in the tunnel at the interface where the N- and C-terminal domains associate
UPF 648
-
-
UPF 648
-
in vivo inhibition
UPF 648
-
in vivo inhibition
UPF 648
UPF 648 binds close to the FAD cofactor and perturbs the local active site structure, preventing productive binding of the substrate kynurenine
ZINC19827377
the inhibitor does not cause hydrogen peroxide as a harmful side product
-
ZINC71915355
the inhibitor is both blood brain barrier permeable and does not cause hydrogen peroxide as a harmful side product
-
additional information
kynurenines substituted with a halogen at the 5-position are excellent substrates, with values of kcat and kcat/Km comparable to or higher than kynurenine. Kynurenines substituted in the 3-position are competitive inhibitors, with KI values lower than the Km for kynurenine. Bromination also enhances inhibition. A pharmacophore model of kynurenine monooxygenase is developed, and predicted that 3,4-dichlorohippuric acid would be an inhibitor
-
additional information
-
kynurenines substituted with a halogen at the 5-position are excellent substrates, with values of kcat and kcat/Km comparable to or higher than kynurenine. Kynurenines substituted in the 3-position are competitive inhibitors, with KI values lower than the Km for kynurenine. Bromination also enhances inhibition. A pharmacophore model of kynurenine monooxygenase is developed, and predicted that 3,4-dichlorohippuric acid would be an inhibitor
-
additional information
-
inhibition by various 2-amino-4-aryl-4-oxobut-2-enoic acids and esters at 10 micromolar; inhibition by various 4-aryl-2-hyroxy-4-oxobut-2-enoic acids and esters at 10 micromolar
-
additional information
the molecular mechanism of action of three classes of inhibitors with differentiated binding modes and kinetics is reported. Two inhibitor classes trap the catalytic flavin in a tilting conformation. This correlates with picomolar affinities, increased residence times and an absence of the peroxide production
-
additional information
KMO inhibitors with brain permeability would be predicted to be more efficacious for treating neurodegenerative diseases than peripheral treatment, as inhibition of KMO in the CNS leads to increased neuroprotective KYNA levels as well as decreased levels of neurotoxic metabolites. Virtual screening combined with a prodrug strategy are used to develop brain-permeable KMO inhibitors. Prodrugs are considered as one of the most promising technologies for lead compound optimisation to cross the blood-brain barrier. For KMO inhibitors, one of the main challenges to cross the blood-brain barrier is the acidic centre, which mimics the binding of the carboxyl group of L-KYN
-
additional information
pyridazine derivatives as KMO inhibitors, structure-activity relationship, overview
-
additional information
determinations of inhibition with the purified enzyme and a cell-based assay
-
additional information
enzyme structure and ligand interaction analysis using the crystal structure of hKMO (PDB ID 5X68), library screening from Zinc15 database, detailed overview
-
additional information
research focuses 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. While substrate analogues bind in the active site of KMO and inhibit activity, they also detrimentally result in the formation of cytotoxic hydrogen peroxide by uncoupling the reaction of NAD(P)H and O2
-
additional information
KMO inhibitors with brain permeability would be predicted to be more efficacious for treating neurodegenerative diseases than peripheral treatment, as inhibition of KMO in the CNS leads to increased neuroprotective KYNA levels as well as decreased levels of neurotoxic metabolites. Virtual screening combined with a prodrug strategy are used to develop brain-permeable KMO inhibitors. Prodrugs are considered as one of the most promising technologies for lead compound optimisation to cross the blood-brain barrier. For KMO inhibitors, one of the main challenges to cross the blood-brain barrier is the acidic centre, which mimics the binding of the carboxyl group of L-KYN
-
additional information
synthesis and evaluation of enzyme inhibitors
-
additional information
pyridazine derivatives as KMO inhibitors, structure-activity relationship, overview
-
additional information
-
pyridazine derivatives as KMO inhibitors, structure-activity relationship, overview
-
additional information
-
the specific enzyme activity is not affected by cloricromene in vitro and in vivo in liver and kidney
-
additional information
-
targeted inhibition of KMO is a viable strategy for achieving local elevation of kynurenate concentrations
-
additional information
development and optimization of a series of inhibitors
-
additional information
the molecular mechanism of action of three classes of inhibitors with differentiated binding modes and kinetics is reported. Two inhibitor classes trap the catalytic flavin in a tilting conformation. This correlates with picomolar affinities, increased residence times and an absence of the peroxide production
-
additional information
enzyme structure and ligand interaction analysis using the crystal structure of pfKMO (PDB ID 5NAK), library screening from Zinc15 database, detailed overview
-
additional information
-
inhibition by N-(4-phenylthiazol-2-yl)benzenesulfonamides with various modifications
-
additional information
KMO inhibitors with brain permeability would be predicted to be more efficacious for treating neurodegenerative diseases than peripheral treatment, as inhibition of KMO in the CNS leads to increased neuroprotective KYNA levels as well as decreased levels of neurotoxic metabolites. Virtual screening combined with a prodrug strategy are used to develop brain-permeable KMO inhibitors. Prodrugs are considered as one of the most promising technologies for lead compound optimisation to cross the blood-brain barrier. For KMO inhibitors, one of the main challenges to cross the blood-brain barrier is the acidic centre, which mimics the binding of the carboxyl group of L-KYN
-
additional information
determinations of inhibition with the purified enzyme and a cell-based assay, docking studies of KMO representative inhibitors, inhibition mechanism, overview
-
additional information
enzyme structure and ligand interaction analysis using the crystal structure of scKMO (PDB ID 4J34), library screening from Zinc15 database, detailed overview
-
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0.0001
(6-chloro-1H-indazol-1-yl)acetic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000026
(6-chloro-5,7-dimethyl-3-oxo-2,3-dihydro-4H-1,4-benzoxazin-4-yl)acetic acid
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.0000025
(R)-3-(5-chloro-2-oxo-6-(1-(pyridin-2-yl)ethoxy)benzo[d]oxazol-3(2H)-yl)propanoate
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.00025
(S)-3-(5-Chloro-2-oxo-6-(1-(pyridin-2-yl)ethoxy)benzo[d]oxazol-3(2H)-yl)propanoate
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.0000286
1-cyclopentyl-N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)methanesulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000387
2,2,2-trifluoro-N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)ethane-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.00004
2-(3,4-dichlorobenzoyl)cyclopropane-1-carboxylic acid
Mus musculus
pH and temperature not specified in the publication
-
0.0000038 - 0.000009
2-(benzyloxy)-5-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
-
0.0025
2-amino-3-(6-chloro-1H-indazol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000034
3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
-
0.000037
3,4-dimethoxy-N-[4-(3-nitrophenyl)thiazol-2-yl]benzenesulfonamide
Homo sapiens
pH and temperature not specified in the publication
0.02
3,4-dimethoxy-N-[5-(3-nitrophenyl)-4-[(piperidin-1-yl)methyl]-1,3-thiazol-2-yl]benzene-1-sulfonamide
-
0.0063
3-(1H-indazol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00016 - 0.00057
3-(4-methyl-5-phenyl-1H-pyrazol-1-yl)benzoic acid
-
0.0000063
3-(5,6-dichloro-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000063
3-(5,6-dichloro-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)-propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000025
3-(5-chloro-1,2-benzoxazol-3-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.001
3-(5-chloro-1H-indazol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000013
3-(5-chloro-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0001
3-(5-chloro-6-cyano-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000032
3-(5-chloro-6-cyclopropoxy-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000005
3-(5-chloro-6-ethoxy-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000005
3-(5-chloro-6-ethoxy-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.00001
3-(5-chloro-6-ethyl-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00001
3-(5-chloro-6-ethyl-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000013
3-(5-chloro-6-methoxy-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000013
3-(5-chloro-6-methoxy-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)-propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000013
3-(5-chloro-6-methyl-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000126
3-(5-chloro-6-methyl-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl)propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.0000023
3-(5-chloro-6-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl)propanoic acid
-
0.000063
3-(5-chloro-7-methyl-2-oxo-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00063
3-(5-cyano-2-methylidene-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.001
3-(5-methoxy-2-methylidene-1,3-benzoxazol-3(2H)-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000398
3-(6-bromo-1H-indazol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0005
3-(6-chloro-1H-benzotriazol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0006
3-(6-chloro-1H-indazol-1-yl)-2-hydroxypropanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0025
3-(6-chloro-1H-indazol-1-yl)-2-methylpropanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.005
3-(6-chloro-1H-indazol-1-yl)butanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00005
3-(6-chloro-1H-indazol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00013
3-(6-chloro-1H-indol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.002
3-(6-chloro-3-methyl-1H-indazol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000079
3-(6-chloro-3-oxo-3,4-dihydro-2H-1-benzopyran-4-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0032
3-(6-methyl-1H-indazol-1-yl)propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000033
3-(dimethylamino)-N-(6-[2-(pyrrolidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.005
3-[2-methylidene-5-(trifluoromethyl)-1,3-benzoxazol-3(2H)-yl]propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.00000071 - 0.00015
3-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
-
0.0001
3-[5-chloro-2-oxo-6-(propan-2-yl)-1,3-benzoxazol-3(2H)-yl]propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000032
3-[5-chloro-2-oxo-6-(pyridin-2-ylmethoxy)-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.0000398
3-[5-chloro-2-oxo-6-(trifluoromethyl)-1,3-benzoxazol-3(2H)-yl]propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000013
3-[5-chloro-2-oxo-6-[(1R)-1-(pyridazin-3-yl)ethoxy]-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000002
3-[5-chloro-2-oxo-6-[(1R)-1-(pyridin-2-yl)ethoxy]-2,3-dihydro-1,3-benzothiazol-3-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000005
3-[5-chloro-2-oxo-6-[(1R)-1-(pyrimidin-2-yl)ethoxy]-2,3-dihydro-1,3-benzoxazol-3-yl]-propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000079
3-[5-chloro-2-oxo-6-[(propan-2-yl)oxy]-1,3-benzoxazol-3(2H)-yl]propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000032
3-[5-chloro-2-oxo-6-[1-(pyridin-2-yl)ethoxy]-2,3-dihydro-1,3-benzoxazol-3-yl]-propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000794
3-[5-chloro-2-oxo-6-[2-(pyrrolidin-1-yl)ethoxy]-2,3-dihydro-1,3-benzoxazol-3-yl]-propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000032
3-[5-chloro-6-(2-methoxyethoxy)-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000013
3-[5-chloro-6-(2-methylpropyl)-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000025
3-[5-chloro-6-(cyclobutylmethoxy)-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.00001
3-[5-chloro-6-(cyclopropylmethoxy)-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]-propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.0000032
3-[5-chloro-6-(cyclopropyloxy)-2-oxo-1,3-benzoxazol-3(2H)-yl]propanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.0000032
3-[5-chloro-6-[(1R)-1-(1,3-oxazol-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.00000398
3-[5-chloro-6-[(1R)-1-(4-methylpyridin-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.0000032
3-[5-chloro-6-[(1R)-1-(5-chloropyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl]-propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.00000316
3-[5-chloro-6-[(1R)-1-(5-chloropyridin-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.0000032
3-[5-chloro-6-[(1R)-1-(5-fluoropyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.0000025
3-[5-chloro-6-[(1R)-1-(5-fluoropyridin-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.0000032
3-[5-chloro-6-[(1R)-1-(5-methylpyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl]-propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.00000316
3-[5-chloro-6-[(1R)-1-(5-methylpyridin-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000002
3-[5-chloro-6-[(1R)-1-(6-methylpyridazin-3-yl)ethoxy]-1,2-benzoxazol-3-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000005
3-[5-chloro-6-[(1R)-1-(6-methylpyridin-2-yl)ethoxy]-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000005
3-[5-chloro-6-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000025
3-[6-(benzyloxy)-5-chloro-2-oxo-2,3-dihydro-1,3-benzoxazol-3-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000005
3-[6-chloro-3-oxo-7-[(1R)-1-(pyridin-2-yl)ethoxy]-3,4-dihydro-2H-1,4-benzoxazin-4-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.00000316
3-[6-chloro-5-[(1R)-1-(pyridin-2-yl)ethoxy]-1H-indazol-1-yl]propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000005
3-[6-chloro-5-[(1R)-1-(pyridin-2-yl)ethoxy]-1H-indol-1-yl]-propanoic acid
Pseudomonas fluorescens
pH and temperature not specified in the publication
0.000025
4-(3,4-dichlorophenyl)-4-oxobutanoic acid
Homo sapiens
-
pH 7.4, 25°C
0.003
4-(6-chloro-1H-indazol-1-yl)butanoic acid
Homo sapiens
pH and temperature not specified in the publication
0.000019
4-amino-N-[4-(2-fluoro-5-trifluoromethyl-phenyl)-thiazol-2-yl]-benzenesulfonamide
Homo sapiens
pH and temperature not specified in the publication
-
0.0000017 - 0.000014
4-chloro-2-([5-chloro-2-(5-methoxy-1,3-dihydro-2H-isoindol-2-yl)-1,3-thiazole-4-carbonyl](methyl)amino)-5-fluorobenzoic acid
-
0.0001
4-methyl-N-(6-[2-(4-methylpiperazin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.0000039
4-methyl-N-(6-[2-(morpholin-4-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.0000014 - 0.0000024
4-methyl-N-(6-[2-(piperidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
-
0.0000027
4-methyl-N-(6-[2-(pyrrolidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.0000291
4-methyl-N-[6-(1-methyl-1H-indol-7-yl)pyridazin-3-yl]benzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.0000169
4-methyl-N-[6-(1-methyl-2,3-dihydro-1H-indol-7-yl)pyridazin-3-yl]benzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.0000087
4-methyl-N-[6-(quinolin-8-yl)pyridazin-3-yl]benzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.0000068 - 0.00013
6-[3-(4-chloro-3-fluorophenyl)pyridin-2-yl]-1-methylquinazoline-2,4(1H,3H)-dione
-
0.0000005
6-[4-chloro-3-(cyclopropyloxy)phenyl]pyrimidine-4-carboxylic acid
-
0.0000007 - 0.0000023
GSK366
0.0000027 - 0.000003
GSK775
0.0000036 - 0.0000043
GSK891
0.0015
ianthellamide A
Homo sapiens
pH and temperature not specified in the publication
-
0.0000045
N-(6-[2-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.0000061
N-(6-[2-fluoro-6-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000825
N-(6-[3-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.02
N-(6-[3-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.000546
N-(6-[4-(dimethylamino)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.0000341
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxan-2-yl)methanesulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000179
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxan-3-yl)methanesulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000128
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxan-4-yl)methanesulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.000041
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-1-(oxolan-2-yl)methanesulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000839
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-2-methoxyethane-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000616
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-3-methoxypropane-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000091
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000272
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)butane-2-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.000116
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)ethanesulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000371
N-(6-[4-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)propane-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000042
N-(6-[5-fluoro-2-(piperidin-1-yl)phenyl]pyridazin-3-yl)-4-methylbenzene-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000292
N-[6-(2-ethylphenyl)pyridazin-3-yl]-4-methylbenzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.0000365
N-[6-(2-methoxyphenyl)pyridazin-3-yl]-4-methylbenzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.000118
N-[6-(3-chlorophenyl)pyridazin-3-yl]-2-(dimethylamino)benzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.0000317
N-[6-(3-chlorophenyl)pyridazin-3-yl]-3-(dimethylamino)benzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.000101
N-[6-(3-chlorophenyl)pyridazin-3-yl]-3-methylbenzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.000402
N-[6-(3-chlorophenyl)pyridazin-3-yl]-4-(dimethylamino)benzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.0000472
N-[6-(isoquinolin-8-yl)pyridazin-3-yl]-4-methylbenzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.000035
Ro 61-8048
Homo sapiens
-
pH 7.4, 25°C
0.0000003 - 0.000074
UPF 648
0.0000038
2-(benzyloxy)-5-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
Homo sapiens
pH 7.9, 37°C
-
0.000009
2-(benzyloxy)-5-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
Rattus norvegicus
pH 7.9, 37°C
-
0.000034
3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Mus musculus
pH and temperature not specified in the publication
-
0.000034
3,4-dimethoxy-N-[4-(3-nitrophenyl)-1,3-thiazol-2-yl]benzene-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.02
3,4-dimethoxy-N-[5-(3-nitrophenyl)-4-[(piperidin-1-yl)methyl]-1,3-thiazol-2-yl]benzene-1-sulfonamide
Mus musculus
pH and temperature not specified in the publication
-
0.02
3,4-dimethoxy-N-[5-(3-nitrophenyl)-4-[(piperidin-1-yl)methyl]-1,3-thiazol-2-yl]benzene-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.00016
3-(4-methyl-5-phenyl-1H-pyrazol-1-yl)benzoic acid
Homo sapiens
pH 7.9, 37°C
-
0.00057
3-(4-methyl-5-phenyl-1H-pyrazol-1-yl)benzoic acid
Rattus norvegicus
pH 7.9, 37°C
-
0.0000023
3-(5-chloro-6-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl)propanoic acid
Mus musculus
pH and temperature not specified in the publication
-
0.0000023
3-(5-chloro-6-[(1R)-1-(pyridin-2-yl)ethoxy]-1,2-benzoxazol-3-yl)propanoic acid
Homo sapiens
pH not specified in the publication, 37°C
-
0.00000071
3-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
Homo sapiens
pH 7.9, 37°C
-
0.00015
3-[5-(4-chloro-3-fluorophenyl)-4-methyl-1H-pyrazol-1-yl]benzoic acid
Rattus norvegicus
pH 7.9, 37°C
-
0.0000017
4-chloro-2-([5-chloro-2-(5-methoxy-1,3-dihydro-2H-isoindol-2-yl)-1,3-thiazole-4-carbonyl](methyl)amino)-5-fluorobenzoic acid
Rattus norvegicus
pH 7.9, 37°C
-
0.000014
4-chloro-2-([5-chloro-2-(5-methoxy-1,3-dihydro-2H-isoindol-2-yl)-1,3-thiazole-4-carbonyl](methyl)amino)-5-fluorobenzoic acid
Homo sapiens
pH 7.9, 37°C
-
0.0000014
4-methyl-N-(6-[2-(piperidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
Mus musculus
brain enzyme, pH and temperature not specified in the publication
-
0.0000024
4-methyl-N-(6-[2-(piperidin-1-yl)phenyl]pyridazin-3-yl)benzene-1-sulfonamide
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000068
6-[3-(4-chloro-3-fluorophenyl)pyridin-2-yl]-1-methylquinazoline-2,4(1H,3H)-dione
Homo sapiens
pH 7.9, 37°C
-
0.00013
6-[3-(4-chloro-3-fluorophenyl)pyridin-2-yl]-1-methylquinazoline-2,4(1H,3H)-dione
Rattus norvegicus
pH 7.9, 37°C
-
0.0000005
6-[4-chloro-3-(cyclopropyloxy)phenyl]pyrimidine-4-carboxylic acid
Mus musculus
pH and temperature not specified in the publication
-
0.0000005
6-[4-chloro-3-(cyclopropyloxy)phenyl]pyrimidine-4-carboxylic acid
Homo sapiens
pH not specified in the publication, 37°C
-
0.0000007
GSK366
Pseudomonas fluorescens
pH 7.5, temperature not specified in the publication
0.0000023
GSK366
Homo sapiens
pH 7.5, temperature not specified in the publication
0.00001
GSK428
Homo sapiens
pH 7.5, temperature not specified in the publication
0.00006
GSK428
Pseudomonas fluorescens
pH 7.5, temperature not specified in the publication
0.0000027
GSK775
Homo sapiens
pH 7.5, temperature not specified in the publication
0.000003
GSK775
Pseudomonas fluorescens
pH 7.5, temperature not specified in the publication
0.0000036
GSK891
Homo sapiens
pH 7.5, temperature not specified in the publication
0.0000043
GSK891
Pseudomonas fluorescens
pH 7.5, temperature not specified in the publication
0.0000003
UPF 648
Homo sapiens
-
pH 7.4, 25°C
0.000074
UPF 648
Saccharomyces cerevisiae
pH 8.0, 30°C
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drug target
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
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 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
malfunction
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
-
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
hKMO is inactive without its membrane targeting domain
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
-
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
-
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
-
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
Mus musculus C57BL/6N x C57BL/6J
-
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
-
metabolism
enzyme of the kynurenine pathway, which is the major catabolic route of tryptophan
metabolism
key enzyme of tryptophan metabolism
metabolism
key enzyme of tryptophan metabolism
metabolism
pivotal enzyme in kynurenine pathway
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 involved in tryptophan catabolism
metabolism
the enzyme is very important in kynurenine pathway because it catalyzes the decisive step in production of metabolites as quinolinic acid
metabolism
-
BcKMO is involved in cAMP and MAPK signaling pathways
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
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BcKMO is involved in cAMP and MAPK signaling pathways
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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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physiological function
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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
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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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additional information
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
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E366Q
2% of the enzyme activity compared with that of the wild-type enzyme
M367A
2% of the enzyme activity compared with that of the wild-type enzyme
M367L
13% of the enzyme activity compared with that of the wild-type enzyme
N363A
28% of the enzyme activity compared with that of the wild-type enzyme
N363D
no activity detected
N465A
about 80% of the enzyme activity compared with that of the wild-type enzyme
R85A
no activity detected
R85K
1% of the enzyme activity compared with that of the wild-type enzyme
Y398A
1% of the enzyme activity compared with that of the wild-type enzyme
Y398F
1% of the enzyme activity compared with that of the wild-type enzyme
Y99A
no activity detected
Y99F
7% of the enzyme activity compared with that of the wild-type enzyme
E366A
site-directed mutagenesis, mutation of a catalytic residue, inactive mutant
Y194A
site-directed mutagenesis, mutation of a catalytic residue, inactive mutant
Y99A
site-directed mutagenesis, mutation of a catalytic residue, inactive mutant
E372A
about 15% of the enzyme activity compared with that of the wild-type enzyme
E372Q
about 5% of the enzyme activity compared with that of the wild-type enzyme
M373A
no activity detected
M373L
about 60% of the enzyme activity compared with that of the wild-type enzyme
N369A
about 65% of the enzyme activity compared with that of the wild-type enzyme
N369D
no activity detected
Q424A
mutation does not greatly affect enzyme activity. Ro 61-8048 shows no inhibition to the pfKMO mutant enzyme
R84A
no activity detected
Y404A
no activity detected
Y404F
about 40% of the enzyme activity compared with that of the wild-type enzyme
Y98A
no activity detected
Y98F
about 1% of the enzyme activity compared with that of the wild-type enzyme
D184A
site-directed mutagenesis, the mutation weakens the beta-sheet dimer interface of the enzyme
Q187A
site-directed mutagenesis, the mutation weakens the beta-sheet dimer interface of the enzyme
R380A
site-directed mutagenesis, the mutation has no effect on kynurenine hydroxylation, suggesting that residue R380 does not play a major role in substrate recognition
Y185P
site-directed mutagenesis, the mutation weakens the beta-sheet dimer interface of the enzyme
additional information
an inactive mutant lacks 162 nucleotides near the 3'-end of the mutant allele, the in-frame deletion results in loss of 54 amino acids leading to loss of enzyme activity and white eyes
additional information
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an inactive mutant lacks 162 nucleotides near the 3'-end of the mutant allele, the in-frame deletion results in loss of 54 amino acids leading to loss of enzyme activity and white eyes
additional information
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an inactive mutant lacks 162 nucleotides near the 3'-end of the mutant allele, the in-frame deletion results in loss of 54 amino acids leading to loss of enzyme activity and white eyes
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additional information
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enzyme deficiency leads to the white eyes and white eggs w-1 phenotype in mutant silkworms, it can be partially rescued by expression of wild-type enzyme under control of either the cytoplasmic actin gene promoter, A3KMO, or the native KMO gene promoter, KKMO, phenotypes, overview
additional information
enzyme deficiency leads to the white eyes and white eggs w-1 phenotype in mutant silkworms, it can be partially rescued by expression of wild-type enzyme under control of either the cytoplasmic actin gene promoter, A3KMO, or the native KMO gene promoter, KKMO, phenotypes, overview
additional information
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enzyme deficiency leads to the white eyes and white eggs w-1 phenotype in mutant silkworms, it can be partially rescued by expression of wild-type enzyme under control of either the cytoplasmic actin gene promoter, A3KMO, or the native KMO gene promoter, KKMO, phenotypes, overview
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additional information
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pathogenic mutant BCG183 is obtained by screening the T-DNA insertion library of Botrytis cinerea. Semiquantitative RT-PCR is used to determine the expression levels of the T-DNA insert gene and confirm the presence of the mutant gene in the mutant BCG183. The pathogenicity-related gene BcKMO, which encodes kynurenine 3-monooxygenase (KMO), is isolated and identified via thermal asymmetric interlaced PCR, bioinformatics analyses, and KMO activity measurement. The mutant BCG183 grows slowly, does not produce conidia and sclerotia, has slender hyphae, and presents enhanced pathogenicity. The phenotype and pathogenicity of the BcKMO complementing mutant (BCG183/BcKMO) are similar to those of the wild-type strain. The wild-type and BCG183/BcKMO colonies are taupe-colored and produce large amounts of sclerotia, while mutant the BCG183 colonies are gray and do not produce sclerotia. The BCG183 mycelia are white and slender with shorter transverse septa, when compared with wild-type and BCG183/BcKMO mycelia. The BCG183 mutant do not produce conidia, whereas the wild-type and BCG183/BcKMO strains do. The BCG183 mutant exhibits remarkably higher sensitivity to NaCl and KCl, when compared with the wild-type. Also, the sensitivity of the mutant BCG183 to fluconazole, Congo Red, menadione, and H2O2 is significantly weaker, when compared with that of the wild-type and BCG183/BcKMO strains. The BCG183 mutant sensitivity to SQ22536 and U0126, inhibitors of the cAMP and MAPK signaling pathways, is significantly weaker, when compared with that of wild-type and BCG183/BcKMO strains. The cAMP content in the mutant BCG183 is significantly lower, when compared with that in wild-type and BCG183/BcKMO strains
additional information
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pathogenic mutant BCG183 is obtained by screening the T-DNA insertion library of Botrytis cinerea. Semiquantitative RT-PCR is used to determine the expression levels of the T-DNA insert gene and confirm the presence of the mutant gene in the mutant BCG183. The pathogenicity-related gene BcKMO, which encodes kynurenine 3-monooxygenase (KMO), is isolated and identified via thermal asymmetric interlaced PCR, bioinformatics analyses, and KMO activity measurement. The mutant BCG183 grows slowly, does not produce conidia and sclerotia, has slender hyphae, and presents enhanced pathogenicity. The phenotype and pathogenicity of the BcKMO complementing mutant (BCG183/BcKMO) are similar to those of the wild-type strain. The wild-type and BCG183/BcKMO colonies are taupe-colored and produce large amounts of sclerotia, while mutant the BCG183 colonies are gray and do not produce sclerotia. The BCG183 mycelia are white and slender with shorter transverse septa, when compared with wild-type and BCG183/BcKMO mycelia. The BCG183 mutant do not produce conidia, whereas the wild-type and BCG183/BcKMO strains do. The BCG183 mutant exhibits remarkably higher sensitivity to NaCl and KCl, when compared with the wild-type. Also, the sensitivity of the mutant BCG183 to fluconazole, Congo Red, menadione, and H2O2 is significantly weaker, when compared with that of the wild-type and BCG183/BcKMO strains. The BCG183 mutant sensitivity to SQ22536 and U0126, inhibitors of the cAMP and MAPK signaling pathways, is significantly weaker, when compared with that of wild-type and BCG183/BcKMO strains. The cAMP content in the mutant BCG183 is significantly lower, when compared with that in wild-type and BCG183/BcKMO strains
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additional information
cinnabar null cn3 line analysis, the aspect ratio and Feret's diameter are increased in cn3 flies compared to Canton S control flies, reflecting mitochondrial elongation arising from KMO deficiency. Mitochondrial respiratory capacity and locomotor activity are decreased in cn flies, independent from 3-hydroxy-L-kynurenine (3-HK) synthesis. Gene cinnabar silencing with about 80% knockdown resulting in an elongation of the mitochondrial network compared with cells treated with the control dsRNAi construct, phenotype overview. Drp1 upregulation reverses climbing phenotype of cn-deficient flies
additional information
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cinnabar null cn3 line analysis, the aspect ratio and Feret's diameter are increased in cn3 flies compared to Canton S control flies, reflecting mitochondrial elongation arising from KMO deficiency. Mitochondrial respiratory capacity and locomotor activity are decreased in cn flies, independent from 3-hydroxy-L-kynurenine (3-HK) synthesis. Gene cinnabar silencing with about 80% knockdown resulting in an elongation of the mitochondrial network compared with cells treated with the control dsRNAi construct, phenotype overview. Drp1 upregulation reverses climbing phenotype of cn-deficient flies
additional information
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cinnabar null cn3 line analysis, the aspect ratio and Feret's diameter are increased in cn3 flies compared to Canton S control flies, reflecting mitochondrial elongation arising from KMO deficiency. Mitochondrial respiratory capacity and locomotor activity are decreased in cn flies, independent from 3-hydroxy-L-kynurenine (3-HK) synthesis. Gene cinnabar silencing with about 80% knockdown resulting in an elongation of the mitochondrial network compared with cells treated with the control dsRNAi construct, phenotype overview. Drp1 upregulation reverses climbing phenotype of cn-deficient flies
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additional information
the enzyme is systematically truncated according to the sequence alignments and the predicted secondary structures. For the truncations 1-377, 1-379, and 1-394, which have 1 or 2 more predicted alpha-helices than that of the 1-372/374, no or weak protein expression is detected. Although for the truncation 1-430 that has the C-terminal hydrophobic tail removed, no enzymatic activities can be detected but the protein expression is normal. The results indicate that the C-terminal portion is important for both the folding and the enzymatic activity
additional information
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the enzyme is systematically truncated according to the sequence alignments and the predicted secondary structures. For the truncations 1-377, 1-379, and 1-394, which have 1 or 2 more predicted alpha-helices than that of the 1-372/374, no or weak protein expression is detected. Although for the truncation 1-430 that has the C-terminal hydrophobic tail removed, no enzymatic activities can be detected but the protein expression is normal. The results indicate that the C-terminal portion is important for both the folding and the enzymatic activity
additional information
generation of a C-terminal domain truncated human KMO whose membrane targeting sequence in its C-terminal domain is suggested to be an essential part of its catalysis
additional information
analysis of kynurenine pathway (KP) metabolism in the brain after depleting microglial cells pharmacologically with the colony stimulating factor 1 receptor inhibitor PLX5622. Young adult mice are fed PLX5622 for 21 days and are euthanized either on the next day or after receiving normal chow for an additional21 days. Expression of microglial marker genes is dramatically reduced on day 22 but has fully recovered by day 43. In both groups, PLX5622 treatment fails to affect Kmo expression, KMO activity or tissue levels of 3-HK and KYNA in the brain. In a parallel experiment, PLX5622 treatment also does not reduce KMO activity, 3-HK and KYNA in the brain of R6/2 mice (a model of HD with activated microglia). With freshly isolated mouse cells ex vivo, KMO is found only in microglia and neurons but not in astrocytes. Neurons contain a large proportion of functional KMO in the adult mouse brain under both physiological and pathological conditions
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
additional information
the KMO expression is effectively inhibited using small interfering RNA (siRNA) and short hairpin RNA (shRNA), respectively. HSV-1 replication is significantly enhanced in KMO-knockdown cells compared to wild-type cells. Overexpression of catalytically inactive KMO catalytic residues mutants has no significant inhibition effect on HSV-1 infection
additional information
Mus musculus C57BL/6N x C57BL/6J
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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
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additional information
generation of a C-terminal domain truncated human KMO whose membrane targeting sequence in its C-terminal domain is suggested to be an essential part of its catalysis
additional information
generation of a C-terminal domain truncated human KMO whose membrane targeting sequence in its C-terminal domain is suggested to be an essential part of its catalysis
additional information
construction of C-terminal truncation mutants KMODELTAC10, KMODELTAC20, KMODELTAC30, KMODELTAC50, and KMODELTAC70, that are all localized in the cytosol after recombinant expression in COS-7 cells, exept for KMODELTAC10. Two forms of C-terminal truncation, KMODELTAC10D and KMODELTAC20D retain almost full activity but KMODELTAC30D shows 1.6fold higher activity than the wild-type. The activities of KMODELTAC50 and KMODELTAC70 is highly reduced, overview. The quantity of expressed KMODELTA30D in COS-7 cellsis 1.3fold higher than the wild-type KMO
additional information
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construction of C-terminal truncation mutants KMODELTAC10, KMODELTAC20, KMODELTAC30, KMODELTAC50, and KMODELTAC70, that are all localized in the cytosol after recombinant expression in COS-7 cells, exept for KMODELTAC10. Two forms of C-terminal truncation, KMODELTAC10D and KMODELTAC20D retain almost full activity but KMODELTAC30D shows 1.6fold higher activity than the wild-type. The activities of KMODELTAC50 and KMODELTAC70 is highly reduced, overview. The quantity of expressed KMODELTA30D in COS-7 cellsis 1.3fold higher than the wild-type KMO
additional information
construction of mutants lacking functional enzyme via RNA interference, RNAi, the gene is unlinked to known eye-color mutants
additional information
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construction of mutants lacking functional enzyme via RNA interference, RNAi, the gene is unlinked to known eye-color mutants
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