Kynurenine

l-Kynurenine
Skeletal formula of L-kynurenine
Ball-and-stick model of the L-kynurenine molecule as a zwitterion
Names
Preferred IUPAC name
(2S)-2-Amino-4-(2-aminophenyl)-4-oxo-butanoic acid
Other names
(S)-Kynurenine
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
MeSH Kynurenine
PubChem CID
UNII
  • 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 check
    Key: YGPSJZOEDVAXAB-QMMMGPOBSA-N check
  • c1ccc(c(c1)C(=O)C[C@@H](C(=O)O)N)N
Properties
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).
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Infobox references

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. Kynurenine and its further breakdown products carry out diverse biological functions, including dilating blood vessels during inflammation and regulating the immune response. Some cancers increase kynurenine production, which increases tumor growth.

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

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

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

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.

Kynurenine pathway dysfunction

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:

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

Drug development

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.

See also