Kynurenine hydroxylase: a potential rate-limiting enzyme in tryptophan metabolism

Bender, David A.; McCreanor, G. M.

doi:10.1042/bst0130441

Cited by 61 publications

(35 citation statements)

References 7 publications

(7 reference statements)

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“…IDO is the first enzyme of this pathway activated by pro-inflammatory cytokines like INF-c (Yasui et al 1986;Mellor and Munn 1999). After tryptophan is catabolised into kynurenine, it is further catabolised into 3-hydroxykynurenine (3HK) by the enzyme kynurenine-3-monooxygenase (KMO) and later to the NMDA-R agonist quinolinic acid (Bender and McCreanor 1985;Chiarugi et al 2001). The kynurenine pathway produces several neuroactive metabolites and can therefore influence neuroprotective and degenerative changes in the central nervous system.…”

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confidence: 99%

Effects of antidepressants and cyclooxygenase-2 inhibitor on cytokines and kynurenines in stimulated in vitro blood culture from depressed patients

et al. 2012

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Stimulation with LPS induced increased production of pro-inflammatory and anti-inflammatory cytokines in both groups, but higher responses in controls. This lower production of cytokine responses in depressed patients indicates that their immune cells are in a refractory phase, induced by a pre-existing pro-inflammatory state. For kynurenines, the whole metabolism was enhanced by LPS; however, an imbalance to neuroprotective metabolites was observed just in control blood. A drug effect could only be shown for imipramine and celecoxib, which were beneficial in terms of re-balancing the immune function but not in re-balancing neuroactive metabolites.

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confidence: 99%

Effects of antidepressants and cyclooxygenase-2 inhibitor on cytokines and kynurenines in stimulated in vitro blood culture from depressed patients

et al. 2012

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“…Thus it may be synthesized into the neurotoxic and apoptotic product 3-hydroxykynurenine (3OHK) by kynurenine-3-monooxygenase (KMO), an enzyme which is induced by the pro-inflammatory cytokine IFNγ (Yasui et al, 1986). 3OHK is also the precursor of the NMDA receptor agonist quinolinic acid (QUIN) that is a potent neurotoxin (Bender and McCreanor, 1985;Chiarugi et al, 2001). Under non-inflammatory conditions, this pathway is balanced by the neuroprotective kynurenic acid (KYNA) pathway in which KYNA acts as an antagonist of the NMDA receptor (Perkins and Stone, 1982) (see Figure 1).…”

Section: The Association Of Immune and Neurochemical Changes In Schizmentioning

confidence: 99%

The metabolic syndrome in schizophrenia: is inflammation a contributing cause?

2012

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This non-systematic review of the literature summarizes the evidence that inflammation plays a major role in the psychopathology of schizophrenia and in the mechanisms that contribute to physical ill health that is commonly associated with schizophrenia. The impact of prenatal infections on the developing brain, the possible genetic link between the human lymphocyte antigen gene, inflammation, heart disease and diabetes, together with the increase in pro-inflammatory cytokines in the blood and cerebrospinal fluid provide convincing evidence that inflammation is a major factor in the pathology of this disorder. The changes in immune-related markers and specific neurotransmitters associated with the positive symptoms of schizophrenia are described. In addition, the possible mechanism whereby structural changes occur in the brain is associated with the neurotoxic effects of pro-inflammatory cytokines, together with the neurotoxic metabolites from the tryptophan-kynurenine pathway that is activated by pro-inflammatory cytokines, is also discussed. The role of effective antipsychotic drug treatment in attenuating the inflammatory response is described. However, evidence is limited regarding the causal connection between atypical antipsychotic drugs and the changes in glucose and lipid metabolism that could trigger the onset of physical ill health, including diabetes and heart disease. Indeed, there is evidence that there is a metabolic predisposition to diabetes in patients with schizophrenia that is exacerbated by obesity and thereby contributes to cardiovascular disease and other co-morbid illnesses. It is concluded that the effects of inflammatory mediators on the brain causally contribute to the pathology of schizophrenia and the ill health that accompanies the disorder.

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“…Dysregulation of the KYN pathway results in up- or downregulation of essential active metabolites and is associated with several neurological disorders [17]. TRP is converted into KYN in the initial and rate-limiting step of the KYN pathway [18], which is catalyzed by either indoleamine 2,3-dioxygenase (IDO) or TRP 2,3-dioxygenase (TDO). TDO is expressed in the liver and uses mainly TRP as a substrate.…”

Section: Introductionmentioning

confidence: 99%

Kynurenine Pathway in Autism Spectrum Disorders in Children

et al. 2017

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Background: There is increasing evidence that altered immune responses play a role in the pathogenesis of autism spectrum disorders (ASD), together with dysfunction of the serotonergic and glutamatergic systems. Since the kynurenine (KYN) pathway that degrades tryptophan (TRP) is activated in various neuroinflammatory states, we aimed to determine whether this pathway is activated in ASD. Methods: Sixty-five pediatric ASD patients (including 52 boys) were enrolled from an epidemiological survey covering 2 counties in Norway; 30 (46.5%) of these patients were diagnosed with childhood autism, 16 (24.6%) with Asperger syndrome, 12 (18.5%) with atypical autism, 1 (1.5%) with Rett syndrome, and 6 (9.2%) with other ASD. The serum levels of the following markers were measured in the children with ASD and compared to those in 30 healthy children: TRP, KYN, kynurenic acid (KA), 3-hydroxykynurenine, and quinolinic acid. Results: The mean serum level of KA was significantly lower in the ASD group than in the healthy controls (28.97 vs. 34.44 nM, p = 0.040), while the KYN/KA ratio was significantly higher in the ASD group (61.12 vs. 50.39, p = 0.006). The same relative values were found when comparing the childhood autism subgroup with the controls. Also, the mean serum level of TRP was significantly lower in children with a subdiagnosis of childhood autism than in those with Asperger syndrome (67.26 vs. 77.79 μM, p = 0.020). Conclusion: Our study indicates that there is an increased neurotoxic potential and also a possible lower KYN aminotransferase activity in ASD.

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Kynurenine hydroxylase: a potential rate-limiting enzyme in tryptophan metabolism

Cited by 61 publications

References 7 publications

Effects of antidepressants and cyclooxygenase-2 inhibitor on cytokines and kynurenines in stimulated in vitro blood culture from depressed patients

Effects of antidepressants and cyclooxygenase-2 inhibitor on cytokines and kynurenines in stimulated in vitro blood culture from depressed patients

The metabolic syndrome in schizophrenia: is inflammation a contributing cause?

Kynurenine Pathway in Autism Spectrum Disorders in Children

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