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Kynurenate

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https://www.readbyqxmd.com/read/29775873/psychosocial-stress-and-inflammation-driving-tryptophan-breakdown-in-children-and-adolescents-a-cross-sectional-analysis-of-two-cohorts
#1
Nathalie Michels, Gerard Clarke, Loreto Olavarria-Ramirez, Sonia Gómez-Martínez, Ligia Esperanza Díaz, Ascensión Marcos, Kurt Widhalm, Livia A Carvalho
BACKGROUND: Tryptophan breakdown is an important mechanism in several diseases e.g. inflammation and stress-induced inflammation have been associated with the development of depression via enhanced tryptophan breakdown. Depression is a major public health problem which commonly starts during adolescence, thus identifying underlying mechanisms during early life is crucial in prevention. The aim of this work was to verify whether independent and interacting associations of psychosocial stress and inflammation on tryptophan breakdown already exist in children and adolescents as a vulnerable age group...
May 15, 2018: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29753195/effect-of-l-tryptophan-and-its-metabolites-on-food-passage-from-the-crop-in-chicks
#2
T Tachibana, Y Kadomoto, M S I Khan, R Makino, M A Cline
l-tryptophan (l-Trp), an essential amino acid, is well known as a precursor of 5-hydroxytryptamine (5-HT) and melatonin. In mammals, l-Trp itself has been reported to suppress gastric emptying in mammals. In addition, 5-HT and melatonin are found in the gastrointestinal tract and affect food passage from the digestive tract in mammals. While the function of these factors in mammals is documented, there is little knowledge on their function in the digestive tract of birds. Therefore, the purpose of the present study was to determine if l-Trp and its metabolites affect the crop emptying rate in chicks (Gallus gallus)...
March 16, 2018: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/29728648/salivary-kynurenic-acid-response-to-psychological-stress-inverse-relationship-to-cortical-glutamate-in-schizophrenia
#3
Joshua Chiappelli, Laura M Rowland, Francesca M Notarangelo, S Andrea Wijtenburg, Marian A R Thomas, Ana Pocivavsek, Aaron Jones, Krista Wisner, Peter Kochunov, Robert Schwarcz, L Elliot Hong
Frontal glutamatergic synapses are thought to be critical for adaptive, long-term stress responses. Prefrontal cortices, including the anterior cingulate cortex (ACC) contribute to stress perception and regulation, and are involved in top-down regulation of peripheral glucocorticoid and inflammatory responses to stress. Levels of kynurenic acid (KYNA) in saliva increase in response to psychological stress, and this stress-induced effect may be abnormal in people with schizophrenia. Here we test the hypothesis that ACC glutamatergic functioning may contribute to the stress-induced salivary KYNA response in schizophrenia...
April 18, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29725904/chronic-mild-stress-alters-kynurenine-pathways-changing-the-glutamate-neurotransmission-in-frontal-cortex-of-rats
#4
David Martín-Hernández, Hiram Tendilla-Beltrán, José L M Madrigal, Borja García-Bueno, Juan C Leza, Javier R Caso
Immune stimulation might be involved in the pathophysiology of major depressive disorder (MDD). This stimulation induces indoleamine 2,3-dioxygenase (IDO), an enzyme that reduces the tryptophan bioavailability to synthesize serotonin. IDO products, kynurenine metabolites, exert neurotoxic/neuroprotective actions through glutamate receptors. Thus, we study elements of these pathways linked to kynurenine metabolite activity examining whether antidepressants (ADs) can modulate them. Male Wistar rats were exposed to chronic mild stress (CMS), and some of them were treated with ADs...
May 3, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29725029/sex-differences-in-hippocampal-memory-and-kynurenic-acid-formation-following-acute-sleep-deprivation-in-rats
#5
Annalisa M Baratta, Silas A Buck, Austin D Buchla, Carly B Fabian, Shuo Chen, Jessica A Mong, Ana Pocivavsek
Inadequate sleep is a prevalent problem within our society that can result in cognitive dysfunction. Elevations in kynurenic acid (KYNA), a metabolite of the kynurenine pathway (KP) of tryptophan degradation known to impact cognition, in the brain may constitute a molecular link between sleep loss and cognitive impairment. To test this hypothesis, we investigated the impact of 6 hours of sleep deprivation on memory and KP metabolism (brain and plasma) in male and female rats. Sleep-deprived males were impaired in a contextual memory paradigm, and both sexes were impaired in a recognition memory paradigm...
May 3, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29710037/organ-co-relationship-in-tryptophan-metabolism-and-factors-that-govern-the-biosynthesis-of-nicotinamide-from-tryptophan
#6
Katsumi Shibata
The pathway of tryptophan (Trp)-nicotinamide is very important nutritionally because a vitamin nicotinamide is biosynthesized from an amino acid Trp. Until we started studying the factors that affect the Trp-nicotinamide conversion rate, little data existed. Data obtained from TDO (Trp 2,3-dioxygenase)-KO (knock-out) mice have revealed that mice can biosynthesize a necessary amount of nicotinamide from Trp by indoleamine 2,3-dioxygenase (IDO) even when TDO is lacking. It has also been shown that 3-hydroxyanthranilic acid is a key intermediate...
2018: Journal of Nutritional Science and Vitaminology
https://www.readbyqxmd.com/read/29705534/increasing-kynurenine-brain-levels-reduces-ethanol-consumption-in-mice-by-inhibiting-dopamine-release-in-nucleus-accumbens
#7
Pablo Giménez-Gómez, Mercedes Pérez-Hernández, María Dolores Gutiérrez-López, Rebeca Vidal, Cristina Abuin-Martínez, Esther O'Shea, María Isabel Colado
Recent research suggests that ethanol (EtOH) consumption behaviour can be regulated by modifying the kynurenine (KYN) pathway, although the mechanisms involved have not yet been well elucidated. To further explore the implication of the kynurenine pathway in EtOH consumption we inhibited kynurenine 3-monooxygenase (KMO) activity with Ro 61-8048 (100 mg/kg, i.p.), which shifts the KYN metabolic pathway towards kynurenic acid (KYNA) production. KMO inhibition decreases voluntary binge EtOH consumption and EtOH preference in mice subjected to "drinking in the dark" (DID) and "two-bottle choice" paradigms, respectively...
April 18, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29694960/kynurenine-pathway-in-autism-spectrum-disorders-in-children
#8
Vesna Bryn, Robert Verkerk, Ola H Skjeldal, Ola Didrik Saugstad, Heidi Ormstad
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...
April 25, 2018: Neuropsychobiology
https://www.readbyqxmd.com/read/29689093/improvement-of-kynurenine-aminotransferase-ii-inhibitors-guided-by-mimicking-sulfate-esters
#9
Gayan S Jayawickrama, Alireza Nematollahi, Guanchen Sun, William Bret Church
The mammalian kynurenine aminotransferase (KAT) enzymes are a family of related isoforms that are pyridoxal 5'-phosphate-dependent, responsible for the irreversible transamination of kynurenine to kynurenic acid. Kynurenic acid is implicated in human diseases such as schizophrenia where it is found in elevated levels and consequently KAT-II, as the isoform predominantly responsible for kynurenic acid production in the brain, has been targeted for the development of specific inhibitors. One class of compounds that have also shown inhibitory activity towards the KAT enzymes are estrogens and their sulfate esters...
2018: PloS One
https://www.readbyqxmd.com/read/29686862/tryptophan-metabolic-profile-in-term-and-preterm-breast-milk-implications-for-health
#10
Louise O'Rourke, Gerard Clarke, Aoife Nolan, Claire Watkins, Timothy G Dinan, Catherine Stanton, R Paul Ross, Cornelius Anthony Ryan
Breast milk is the only source of the essential amino acid tryptophan (TRP) in breast-fed infants. Low levels of TRP could have implications for infant neurodevelopment. The objectives of the present study were to compare the relationship of TRP and its neuroactive pathway metabolites kynurenine (Kyn) and kynurenic acid (KynA) in preterm and term expressed breast milk (EBM) in the first 14 d following birth, and the relationship of TRP metabolism to maternal stress and immune status. A total of twenty-four mothers were recruited from Cork University Maternity Hospital: twelve term (>38 weeks) and twelve preterm (<35 weeks)...
2018: Journal of Nutritional Science
https://www.readbyqxmd.com/read/29619629/effect-of-kynurenic-acid-on-pupae-viability-of-drosophila-melanogaster-cinnabar-and-cardinal-eye-color-mutants-with-altered-tryptophan-kynurenine-metabolism
#11
Valeriya Navrotskaya, Artur Wnorowski, Waldemar Turski, Gregory Oxenkrug
Kynurenic acid (KYNA) is one of the metabolites of evolutionary conserved tryptophan (Trp)/kynurenine (Kyn) metabolic pathway. Elevation of KYNA contributes to development of psychosis in schizophrenia but attenuates neurodegeneration in Drosophila model of Huntington's disease. We have reported that KYNA increased lethality of pupae of wild-type flies, but not of vermilion (v) mutants with impaired formation of Kyn from Trp, suggesting that KYNA toxicity depends on its interaction with downstream Kyn metabolites [i...
April 4, 2018: Neurotoxicity Research
https://www.readbyqxmd.com/read/29608993/kynurenine-pathway-in-depression-a-systematic-review-and-meta-analysis
#12
REVIEW
Kamiyu Ogyu, Kaoruhiko Kubo, Yoshihiro Noda, Yusuke Iwata, Sakiko Tsugawa, Yuki Omura, Masataka Wada, Ryosuke Tarumi, Eric Plitman, Sho Moriguchi, Takahiro Miyazaki, Hiroyuki Uchida, Ariel Graff-Guerrero, Masaru Mimura, Shinichiro Nakajima
Abnormalities of the kynurenine (KYN) pathway may be implicated in the pathophysiology of depression. However, the relationships between depression and each metabolite of the KYN pathway remain uncertain. Therefore, we conducted a meta-analysis about the levels of the metabolites of KYN pathway between patients with depression and controls. Out of 899 initial records, we identified 22 articles to form the empirical basis. Seventeen, 10, and 18 studies examined levels of kynurenic acid (KYNA), quinolinic acid (QUIN), and KYN, respectively...
March 30, 2018: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/29605816/regulation-of-kynurenine-metabolism-by-a-ketogenic-diet
#13
Svenja Heischmann, Lindsey B Gano, Kevin Quinn, Li-Ping Liang, Jacek Klepacki, Uwe Christians, Nichole Reisdorph, Manisha Patel
Ketogenic diets (KDs) are increasingly utilized as treatments for epilepsy, other neurological diseases, and cancer. Despite their long history in suppressing seizures, the distinct molecular mechanisms of action of KDs are still largely unknown. The goal of this study was to identify key metabolites and pathways altered in hippocampus and plasma of rats fed a KD vs. control diet either ad libitum or calorically restricted to 90% of the recommended intake. This was accomplished using a combination of targeted methods and untargeted mass spectrometry-based metabolomics analyses...
March 31, 2018: Journal of Lipid Research
https://www.readbyqxmd.com/read/29603794/identification-of-metabolites-in-plasma-for-predicting-survival-in-glioblastoma
#14
Jie Shen, Renduo Song, Tiffany R Hodges, Amy B Heimberger, Hua Zhao
Circulating metabolomics profiling holds prognostic potential. However, such efforts have not been extensively carried out in glioblastoma. In this study, two-step (training and testing) metabolomics profiling was conducted from the plasma samples of 159 glioblastoma patients. Metabolomics profiling was tested for correlation with 2-year overall and disease-free survivals. Arginine, methionine, and kynurenate levels were significantly associated with 2-year overall survival in both the training and testing sets...
March 30, 2018: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/29577176/glutamate-receptors-of-the-a5-region-modulate-cardiovascular-responses-evoked-from-the-dorsomedial-hypothalamic-nucleus-and-perifornical-area
#15
M V López-González, A Díaz-Casares, M González-García, C A Peinado-Aragonés, M A Barbancho, M Carrillo de Albornoz, M S Dawid-Milner
To assess the possible function of glutamate in the interaction between the dorsomedial hypothalamic nucleus-perifornical area (DMH-PeF) and the A5 pontine region (A5), cardiovascular and respiratory changes were studied in response to electrical stimulation of the DMH-PeF (1 ms pulses, 30-50 μA given at 100 Hz for 5 s) before and after the microinjection of kynurenic acid (non-specific glutamate receptor antagonist; 50 nl, 5 nmol), MK-801 (NMDA receptor antagonist; 50 nl, 50 nmol), CNQX (non-NMDA receptor antagonist; 50 nl, 50 nmol) or MCPG (metabotropic glutamate receptor antagonist; 50 nl, 5 nmol) within the A5 region...
March 26, 2018: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/29570959/galantamine-memantine-combination-for-cognitive-impairments-due-to-electroconvulsive-therapy-traumatic-brain-injury-and-neurologic-and-psychiatric-disorders-kynurenic-acid-and-mismatch-negativity-target-engagement
#16
Maju Mathew Koola
Cognitive impairments due to electroconvulsive therapy (ECT), traumatic brain injury (TBI), and neurologic and psychiatric disorders are prevalent. Cholinergic and glutamatergic pathways, α-7 nicotinic acetylcholine (α-7nACh) receptor, and N-methyl-d-aspartate (NMDA) receptor are potential pathophysiologic mechanisms in all of these conditions. Galantamine not only is an acetylcholinesterase inhibitor but has a dual mode of action as a α-7nACh receptor modulator as well. Memantine is a noncompetitive NMDA receptor antagonist...
March 1, 2018: Primary Care Companion to CNS Disorders
https://www.readbyqxmd.com/read/29564809/kynurenic-acid-restores-nrf2-levels-and-prevents-quinolinic-acid-induced-toxicity-in-rat-striatal-slices
#17
Fernanda Silva Ferreira, Helena Biasibetti-Brendler, Paula Pierozan, Felipe Schmitz, Carolina Gessinger Bertó, Caroline Acauan Prezzi, Vanusa Manfredini, Angela T S Wyse
Kynurenic acid (KYNA) and quinolinic acid (QUIN) are metabolites produced in the degradation of tryptophan and have important neurological activities. KYNA/QUIN ratio changes are known to be associated with central nervous system disorders, such Alzheimer, Parkinson, and Huntington diseases. In the present study, we investigate the ability of KYNA in prevent the first events preceding QUIN-induced neurodegeneration in striatal slices of rat. We evaluated the protective effect of KYNA on oxidative status (reactive oxygen species production, antioxidant enzymes activities, lipid peroxidation, nitrite levels, protein and DNA damage, and iNOS immunocontent), mitochondrial function (mitochondrial mass, membrane potential, and respiratory chain enzymes), and Na+ ,K+ -ATPase in striatal slices of rats treated with QUIN...
March 21, 2018: Molecular Neurobiology
https://www.readbyqxmd.com/read/29559921/nitric-oxide-orchestrates-a-power-law-modulation-of-sympathetic-firing-behaviors-in-neonatal-rat-spinal-cords
#18
Chun-Kuei Su, Yi-Yin Chen, Chiu-Ming Ho
Nitric oxide (NO) is a diffusible gas and has multifarious effects on both pre- and postsynaptic events. As a consequence of complex excitatory and inhibitory integrations, NO effects on neuronal activities are heterogeneous. Using in vitro preparations of neonatal rats that retain the splanchnic sympathetic nerves and the thoracic spinal cord as an experimental model, we report here that either enhancement or attenuation of NO production in the neonatal rat spinal cords could increase, decrease, or not change the spontaneous firing behaviors recorded from splanchnic sympathetic single fibers...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29537924/fragment-screening-of-human-kynurenine-aminotransferase-ii
#19
Gayan S Jayawickrama, Alireza Nematollahi, Guanchen Sun, W Bret Church
Kynurenine aminotransferase-II (KAT-II) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that acts in the tryptophan metabolic pathway by catalyzing the transamination of kynurenine into kynurenic acid (KYNA). It is one of four isoforms in the KAT family, of which it is the primary homologue responsible for KYNA production in the mammalian brain. KAT-II is targeted for inhibition as KYNA is implicated in diseases such as schizophrenia, where it is found in elevated concentrations. Previously, many different approaches have been taken to develop KAT-II inhibitors, and herein fragment-based drug design (FBDD) approaches have been exploited to provide further lead compounds that can be designed into novel inhibitors...
March 1, 2018: SLAS Discovery
https://www.readbyqxmd.com/read/29532751/ischemic-stroke-and-kynurenines-medicinal-chemistry-aspects
#20
Peter Hertelendy, Jozsef Toldi, Ferenc Fulop, Laszlo Vecsei
Ischemic stroke is one of the leading causes of mortality and permanent disability in developed countries. Stroke induces massive glutamate release, which in turn causes N-Methyl-D-aspartate (NMDA) receptor over-excitation and thus calcium overload in neurons leading to cell death via apoptotic cascades. The kynurenine pathway is a complex enzymatic cascade of tryptophan catabolism, generating various neuroactive metabolites. One metabolite, kynurenic acid (KYNA), is a potent endogenous NMDA glutamate receptor antagonist, making it a possible therapeutic tool to decrease excitotoxicity and neuroinflammation...
March 12, 2018: Current Medicinal Chemistry
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