Figure: kynurenine pathway
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Function
- metabolic pathway resulting in production of NAD+
- intermediary metabolites include tryptophan, kynurenine, kynurenic acid, xanthurenic acid, quinolinic acid, & 3-hydroxykynurenine[1]
* illustrations of the Kynurenine pathway may be found in[1][2]
Biochemistry
- kynurenine pathway 1
- enzyme: indoleamine-2,3-dioxygenase
- substrate: tryptophan + O2
- product: N-formylkynurenine
- kynurenine pathway 1b
- enzyme: tryptophan-2,3-dioxygenase
- substrate: tryptophan + O2
- product: N-formylkynurenine
- within hepatocyte
- kynurenine pathway 2
- enzyme: formamidase
- substrate: N-formylkynurenine + H2O
- product: kynurenine + formate
- kynurenine pathway 3
- enzyme: kynurenine aminotransferase
- substrate: kynurenine
- product: kynurenate
- kynurenine pathway 3b
- enzyme: alcohol oxidoreductase
- substrate: kynurenate
- product: quinaldate
- kynurenine pathway 4
- enzyme: kynureninase
- substrate: kynurenine + H2O
- product: anthranilate + alanine
- kynurenine pathway 5
- enzyme: Kynurenine-3-monooxygenase
- substrate: kynurenine + O2 + NADPH
- product: 3-hydroxykynurenine + H2O + NADP
- kynurenine pathway 5b
- enzyme: hydroxylase
- substrate: anthranilate + O2 + NADPH
- product: 3-hydroxyanthranilate + H2O + NADP
- occurs in brain
- kynurenine pathway 6
- enzyme: kynurenine aminotransferase
- substrate: 3-hydroxykynurenine
- product: xanthurenate
- kynurenine pathway 6b
- enzyme: alcohol oxidoreductase
- substrate: xanthurenate
- product: 8-hydroxyquinaldate
- kynurenine pathway 7
- enzyme: kynureninase
- substrate: 3-hydroxykynurenine + H2O
- product: 3-hydroxyanthranilate + alanine
- kynurenine pathway 8
- enzyme: 3-hydroxyanthranilate oxygenase
- substrate: 3-hydroxyanthranilate + O2
- product: 2-acroleyl-3-aminofumarate
- kynurenine pathway 8b
- enzyme: oxidoreductase
- substrate: 3-hydroxyanthranilate
- product: 2-aminophenol
- kynurenine pathway 9a
- enzyme: picolinate carboxylase
- substrate: 2-acroleyl-3-aminofumarate
- product: 2-aminomuconic semialdehyde
- kynurenine pathway 9b
- substrate: 2-aminomuconic semialdehyde
- product: picolinate
- spontaneous
- kynurenine pathway 9c
- enzyme: aldehyde oxidoreductase
- substrate: 2-aminomuconic semialdehyde
- product: 2-aminomuconate
- kynurenine pathway 9d
- enzyme: aminotransferase
- substrate: 2-aminomuconate
- product: alpha-ketoadipate
- kynurenine pathway 9e
- enzyme: transferase
- substrate: alpha-ketoadipate + Coenzyme-A
- product: glutaryl-CoA + CO2
- kynurenine pathway 9f
- enzyme: oxidoreductase
- substrate: glutaryl-CoA + Coenzyme-A
- product: 2 acetyl-CoA + CO2
- kynurenine pathway 10
- substrate: 2-acroleyl-3-aminofumarate
- product: quinolinate
- spontaneous
- kynurenine pathway 11
- enzyme: quinolinate phosphoribosyltransferase
- substrate: quinolinate
- product: quinolinate ribonucleotide
- kynurenine pathway 12
References
- ↑ 1.0 1.1 1.2 Wikipedia: Kynurenine_pathway https://en.wikipedia.org/wiki/Kynurenine_pathway
- ↑ 2.0 2.1 Savitz J The kynurenine pathway: a finger in every pie. Mol Psychiatry. 2020 Jan;25(1):131-147 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30980044 PMCID: PMC6790159 Free PMC article
- ↑ Majewski M, Kozlowska A, Thoene M, Lepiarczyk E, Grzegorzewski WJ. Overview of the role of vitamins and minerals on the kynurenine pathway in health and disease. J Physiol Pharmacol. 2016 Feb;67(1):3-19. PMID: https://www.ncbi.nlm.nih.gov/pubmed/27010891 Review.
- ↑ Castro-Portuguez R, Sutphin GL. Kynurenine pathway, NAD+ synthesis, and mitochondrial function: Targeting tryptophan metabolism to promote longevity and healthspan. Exp Gerontol. 2020 Apr;132:110841. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31954874 Free PMC article. Review.
- ↑ Maddison DC, Giorgini F. The kynurenine pathway and neurodegenerative disease. Semin Cell Dev Biol. 2015 Apr;40:134-41. PMID: https://www.ncbi.nlm.nih.gov/pubmed/25773161 Review.
- ↑ Lovelace MD, Varney B, Sundaram G et al Recent evidence for an expanded role of the kynurenine pathway of tryptophan metabolism in neurological diseases. Neuropharmacology. 2017 Jan;112(Pt B):373-388. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26995730 Review.
- ↑ Boros FA, Bohar Z, Vecsei L. Genetic alterations affecting the genes encoding the enzymes of the kynurenine pathway and their association with human diseases. Mutat Res. 2018 Apr-Jun;776:32-45. PMID: https://www.ncbi.nlm.nih.gov/pubmed/29807576 Review.
- ↑ Eastman & Guilarte J Nutr Biochem 3:618 1992
- ↑ Principles of Biochemistry 6th ed., White, Handler, Smith, Hill, & Lehman (eds.) McGraw-Hill, NY 1978, pg 751