ArticleThe Journal of nutrition2013
A mathematical model of tryptophan metabolism via the kynurenine pathway provides insights into the effects of vitamin B-6 deficiency, tryptophan loading, and induction of tryptophan 2,3-dioxygenase on tryptophan metabolites.
Article in The Journal of nutrition, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 51 citations in OpenAlex.
- Pyridoxine supplementation does not alter in vivo kinetics of one-carbon metabolism but modifies patterns of one-carbon and tryptophan metabolites in vitamin B-6-insufficient oral contraceptive users.The American journal of clinical nutrition · 2015Trial
- Metabolite profile analysis reveals association of vitamin B-6 with metabolites related to one-carbon metabolism and tryptophan catabolism but not with biomarkers of inflammation in oral contraceptive users and reveals the effects of oral contraceptives on these processes.The Journal of nutrition · 2015Trial
- Nutritional Interventions for Perimenopausal Anxiety and Depression Targeting Tryptophan and GABA Pathways: A Narrative Review.Nutrients · 2026Review
- Canine Idiopathic Epilepsy as a Natural Animal Model for Human Epilepsy: A Scoping Review Highlighting Metabolic Perspectives Beyond the Brain.Nutrients · 2026Article
- Carboxymethyl Dextran-Based Biosensor for Simultaneous Determination of IDO-1 and IFN-Gamma in Biological Material.Biosensors · 2025Article
- Plasma metabolome reveals altered oxidative stress, inflammation, and amino acid metabolism in dogs with idiopathic epilepsy.Epilepsia · 2025Article
- Metabolomic profiling and identification of potential biomarkers of highly pathogenic avian influenza (H5N1) in chicken.Frontiers in cellular and infection microbiology · 2025Article
- Impact of Substance Use Disorder on Tryptophan Metabolism Through the Kynurenine Pathway: A Narrative Review.Metabolites · 2024Review
- The Biology and Biochemistry of Kynurenic Acid, a Potential Nutraceutical with Multiple Biological Effects.International journal of molecular sciences · 2024Review
- Kynurenic Acid/AhR Signaling at the Junction of Inflammation and Cardiovascular Diseases.International journal of molecular sciences · 2024Review
- Multiple roles of haem in cystathionine β-synthase activity: implications for hemin and other therapies of acute hepatic porphyria.Bioscience reports · 2021Article
- Characterization of the Metabolic Pathways of 4-Chlorobiphenyl (PCB3) in HepG2 Cells Using the Metabolite Profiles of Its Hydroxylated Metabolites.Environmental science & technology · 2021Article
- A model of dopamine and serotonin-kynurenine metabolism in cortisolemia: Implications for depression.PLoS computational biology · 2021Article
- Article
- Pyridoxal 5'-Phosphate-Dependent Enzymes at the Crossroads of Host-Microbe Tryptophan Metabolism.International journal of molecular sciences · 2020Review
- Vitamin B6 and Diabetes: Relationship and Molecular Mechanisms.International journal of molecular sciences · 2020 · on this mapReview
- UPLC/MS/MS-Based Metabolomics Study of the Hepatotoxicity and Nephrotoxicity in Rats Induced byACS omega · 2020Article
- PLPHP deficiency: clinical, genetic, biochemical, and mechanistic insights.Brain : a journal of neurology · 2019Article
- Article
- Metabolomics of Hydrazine-Induced Hepatotoxicity in Rats for Discovering Potential Biomarkers.Disease markers · 2018Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Vitamin B-6 deficiency is associated with impaired tryptophan metabolism because of the coenzyme role of pyridoxal 5'-phosphate (PLP) for kynureninase and kynurenine aminotransferase. To investigate the underlying mechanism, we developed a mathematical model of tryptophan metabolism via the kynurenine pathway. The model includes mammalian data on enzyme kinetics and tryptophan transport from the intestinal lumen to liver, muscle, and brain. Regulatory mechanisms and inhibition of relevant enzymes were included. We simulated the effects of graded reduction in cellular PLP concentration, tryptophan loads and induction of tryptophan 2,3-dioxygenase (TDO) on metabolite profiles and urinary excretion. The model predictions matched experimental data and provided clarification of the response of metabolites in various extents of vitamin B-6 deficiency. We found that moderate deficiency yielded increased 3-hydroxykynurenine and a decrease in kynurenic acid and anthranilic acid. More severe deficiency also yielded an increase in kynurenine and xanthurenic acid and more pronounced effects on the other metabolites. Tryptophan load simulations with and without vitamin B-6 deficiency showed altered metabolite concentrations consistent with published data. Induction of TDO caused an increase in all metabolites, and TDO induction together with a simulated vitamin B-6 deficiency, as has been reported in oral contraceptive users, yielded increases in kynurenine, 3-hydroxykynurenine, and xanthurenic acid and decreases in kynurenic acid and anthranilic acid. These results show that the model successfully simulated tryptophan metabolism via the kynurenine pathway and can be used to complement experimental investigations.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.