ArticleThe Journal of biological chemistry2016
Tetrahydrobiopterin Biosynthesis as a Potential Target of the Kynurenine Pathway Metabolite Xanthurenic Acid.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 57 citations in OpenAlex.
- Research Progress on the Biological Function and Homeostatic Disruption of Microglia in the Pathogenesis of Major Depressive Disorder.Neuroscience bulletin · 2026Review
- Decoding psychotropic-induced metabolic disturbances: gut-brain axis, multi-omics, and nutrition-lifestyle integration.Frontiers in nutrition · 2026Review
- Quinoline Quest: Kynurenic Acid Strategies for Next-Generation Therapeutics via Rational Drug Design.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Redefining Roles: A Paradigm Shift in Tryptophan-Kynurenine Metabolism for Innovative Clinical Applications.International journal of molecular sciences · 2024Review
- Medial prefrontal cortex connectivity with the nucleus accumbens is related to HIV serostatus, perceptions of psychological stress, and monocyte expression of TNF-a.Brain, behavior, & immunity - health · 2024Article
- Treatment-resistant depression: molecular mechanisms and management.Molecular biomedicine · 2024Review
- Pathological shifts in tryptophan metabolism in human term placenta exposed to LPS or poly I:C†.Biology of reproduction · 2024Article
- A Review on the Role and Function of Cinnabarinic Acid, a "Forgotten" Metabolite of the Kynurenine Pathway.Cells · 2024Review
- Phenylalanine metabolism and tetrahydrobiopterin bio-availability in COVID-19 and HIV.Heliyon · 2023Article
- Tryptophan and Substance Abuse: Mechanisms and Impact.International journal of molecular sciences · 2023Review
- Peripheralized sepiapterin reductase inhibition as a safe analgesic therapy.Frontiers in pharmacology · 2023Review
- Biopterin metabolism and nitric oxide recoupling in cancer.Frontiers in oncology · 2023Review
- Tetrahydrobiopterin in Cell Function and Death Mechanisms.Antioxidants & redox signaling · 2022Review
- Establishment of an early diagnosis model of colon cancerous bowel obstruction based on 1H NMR.PloS one · 2022Article
- Aspirin eugenol ester alleviates lipopolysaccharide-induced acute lung injury in rats while stabilizing serum metabolites levels.Frontiers in immunology · 2022Article
- Antibiotics and the Nervous System-Which Face of Antibiotic Therapy Is Real, Dr. Jekyll (Neurotoxicity) or Mr. Hyde (Neuroprotection)?Molecules (Basel, Switzerland) · 2021Review
- Mechanisms of Neuronal Damage in Acute Hepatic Porphyrias.Diagnostics (Basel, Switzerland) · 2021Review
- Article
- Modulation of the Nitric Oxide/BH4 Pathway Protects Against Irradiation-Induced Neuronal Damage.Neurochemical research · 2021Article
- GCH1 induces immunosuppression through metabolic reprogramming and IDO1 upregulation in triple-negative breast cancer.Journal for immunotherapy of cancer · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tryptophan metabolites in the kynurenine pathway are up-regulated by pro-inflammatory cytokines or glucocorticoids, and are linked to anti-inflammatory and immunosuppressive activities. In addition, they are up-regulated in pathologies such as cancer, autoimmune diseases, and psychiatric disorders. The molecular mechanisms of how kynurenine pathway metabolites cause these effects are incompletely understood. On the other hand, pro-inflammatory cytokines also up-regulate the amounts of tetrahydrobiopterin (BH4), an enzyme cofactor essential for the synthesis of several neurotransmitter and nitric oxide species. Here we show that xanthurenic acid is a potent inhibitor of sepiapterin reductase (SPR), the final enzyme in de novo BH4 synthesis. The crystal structure of xanthurenic acid bound to the active site of SPR reveals why among all kynurenine pathway metabolites xanthurenic acid is the most potent SPR inhibitor. Our findings suggest that increased xanthurenic acid levels resulting from up-regulation of the kynurenine pathway could attenuate BH4 biosynthesis and BH4-dependent enzymatic reactions, linking two major metabolic pathways known to be highly up-regulated in inflammation.
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Registered trials
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.