Kynurenine (original) (raw)

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l-Kynurenine

Skeletal formula of L-kynurenine
Ball-and-stick model of the L-kynurenine molecule as a zwitterion
Names
Preferred IUPAC name (2_S_)-2-Amino-4-(2-aminophenyl)-4-oxo-butanoic acid
Other names(S)-Kynurenine
Identifiers
CAS Number 343-65-7 (d/l) ☒N2922-83-0 (l) ☒N13441-51-5 (d) ☒N
3D model (JSmol) Interactive image
ChEBI CHEBI:57959 checkY
ChEMBL ChEMBL498416 checkY
ChemSpider 141580 checkY
DrugBank DB02070 checkY
MeSH Kynurenine
PubChem CID 846 (d/l)1152206 (d)161166 (l)
UNII 02JW4J5R44
CompTox Dashboard (EPA) DTXSID101031182 Edit this at Wikidata
InChI InChI=1S/C10H12N2O3/c11-7-4-2-1-3-6(7)9(13)5-8(12)10(14)15/h1-4,8H,5,11-12H2,(H,14,15)/t8-/m0/s1 checkYKey: YGPSJZOEDVAXAB-QMMMGPOBSA-N checkY
SMILES c1ccc(c(c1)C(=O)C[C@@H](C(=O)O)N)N
Properties
Chemical formula C10H12N2O3
Molar mass 208.217 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). ☒N verify (what is checkY☒N ?) Infobox references

Chemical compound

l-Kynurenine is a metabolite of the amino acid l-tryptophan used in the production of niacin.

Kynurenine is synthesized by the enzyme tryptophan dioxygenase, which is made primarily but not exclusively in the liver, and indoleamine 2,3-dioxygenase, which is made in many tissues in response to immune activation.[1] Kynurenine and its further breakdown products carry out diverse biological functions, including dilating blood vessels during inflammation[2] and regulating the immune response.[3] Some cancers increase kynurenine production, which increases tumor growth.[1]

Kynurenine protects the eye by absorbing UV light, especially in the UVA region (315-400 nm).[4] Kynurenine is present in the lens and retina as one of multiple tryptophan derivatives produced in the eye, including 3-hydroxykynurenine, that together provide UV protection and aid in enhancing visual acuity.[5][6] The use of kynurenine as a UV filter is consistent with its photostability and low photosensitization, owing to its efficient relaxation from the UV-induced excited state.[7] The concentration of this UV filter decreases with age,[8] and this loss of free kynurenine and the concomitant formation of relatively more photosensitizing kynurenine derivatives and kynurenine-protein conjugates may contribute to the formation of cataracts.[9][10][11]

Evidence suggests that increased kynurenine production may precipitate depressive symptoms associated with interferon treatment for hepatitis C.[12] Cognitive deficits in schizophrenia are associated with imbalances in the enzymes that break down kynurenine.[13] Blood levels of kynurenine are reduced in people with bipolar disorder.[14] Kynurenine production is increased in Alzheimer's disease[15][16] and cardiovascular disease[17] where its metabolites are associated with cognitive deficits[18] and depressive symptoms.[19] Kynurenine is also associated with tics.[20][21]

Kynureninase catabolizes the conversion of kynurenine into anthranilic acid[22] while kynurenine-oxoglutarate transaminase catabolizes its conversion into kynurenic acid. Kynurenine 3-hydroxylase converts kynurenine to 3-hydroxykynurenine.[23]

Kynurenine has also been identified as one of two compounds that makes up the pigment that gives the goldenrod crab spider its yellow color.[24]

The kynurenine pathway, which connects quinolinic acid to tryptophan. The pathway is named for the first intermediate, kynurenine, which is a precursor to kynurenic acid and 3-hydroxykynurenine.[25]

Kynurenine pathway dysfunction

[edit]

Dysfunctional states of distinct steps of the kynurenine pathway (such as kynurenine, kynurenic acid, quinolinic acid, anthranilic acid, 3-hydroxykynurenine) have been described for a number of disorders, including:[26]

Downregulation of kynurenine-3-monooxygenase (KMO) can be caused by genetic polymorphisms, cytokines, or both.[29][30] KMO deficiency leads to an accumulation of kynurenine and to a shift within the tryptophan metabolic pathway towards kynurenine acid and anthranilic acid.[31] Kynurenine-3-monooxygenase deficiency is associated with disorders of the brain (e.g. major depressive disorder, bipolar disorder, schizophrenia, tic disorders) [32] and of the liver.[20][33][34][35][36]

It is hypothesized that the kynurenine pathway is partly responsible for the therapeutic effect of lithium on bipolar disorder. If that is the case, it could be a target of drug discovery.[37][38]

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