General Information of MET (ID: META00613)
Name L-3-Hydroxykynurenine
Synonyms   Click to Show/Hide Synonyms of This Metabolite
(2S)-2-Amino-4-(2-amino-3-hydroxyphenyl)-4-oxobutanoate; (2S)-2-Amino-4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid; 3-(2-Amino-3-hydroxybenzoyl)-L-alanine; 3-(3-Hydroxyanthraniloyl)-L-alanine; 3-Hydroxy-L-kynurenine; L-3-HK
Source Endogenous;Yeast Metabolite;Food;Microbial
Structure Type   Carbonyl compounds  (Click to Show/Hide the Complete Structure Type Hierarchy)
Organic oxygen compounds
Organooxygen compounds
Carbonyl compounds
PubChem CID
11811
HMDB ID
HMDB0011631
Formula
C10H12N2O4
Structure
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3D MOL 2D MOL
  Click to Show/Hide the Molecular/Functional Data (External Links/Property/Function) of This Metabolite
KEGG ID
C03227
ChEBI ID
17380
FooDB ID
FDB028330
ChemSpider ID
11318
Physicochemical Properties Molecular Weight 224.21 Topological Polar Surface Area 127
XlogP -2.5 Complexity 282
Heavy Atom Count 16 Rotatable Bond Count 4
Hydrogen Bond Donor Count 4 Hydrogen Bond Acceptor Count 6
Function
L-3-Hydroxykynurenine (L-3-HK) is a metabolite in the kynurenine pathway, the major route of tryptophan degradation in mammals. Kynurenine 3-monooxygenase, an NADPH-dependent flavin monooxygenase, catalyses the hydroxylation of L-kynurenine to L-3-hydroxykynurenine. 3-hydroxykynurenine can be converted to 3-hydroxyanthranilate by the enzyme 3-hydroxykinureninase. It may also be converted to 4-(2-amino-3-hydroxphenyl)-2,4-dioxobutanoate by the enzyme kynurenine-oxoglutarate transaminase. L-3-Hydroxykynurenine (L-3-HK) is a known generator of highly reactive free radicals. An elevation of L-3-HK levels has been shown to constitute a significant hazard in situations of excitotoxic injury. In particular, L-3-HK may contribute to the neuronal deficits underlying HIV-associated dementia. Pharmacological interventions aimed at decreasing L-3-HK formation may therefore be particularly useful for the treatment of neurological diseases which are associated with an abnormally enhanced flux through the kynurenine pathway.
Regulatory Network
Full List of Protein(s) Regulating This Metabolite
      Hydrolases (EC 3)
            Kynureninase (KYNU) Click to Show/Hide the Full List of Regulating Pair(s):   1 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Mutation (c.468T-A, c.1045_1051delTTTAAGC) of KYNU
                      Induced Change L-3-Hydroxykynurenine concentration: increase (FC = 160.7)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hereditary methemoglobinemia [ICD-11: 3A92]
                      Details It is reported that mutation (c.468T-A, c.1045_1051delTTTAAGC) of KYNU leads to the increase of L-3-hydroxykynurenine levels compared with control group.
      Oxidoreductases (EC 1)
            3-hydroxyanthranilate oxygenase (HAAO) Click to Show/Hide the Full List of Regulating Pair(s):   2 Pair(s)
               Detailed Information Protein   Info click to show the details of this protein
               Regulating Pair (1) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Mutation (c.483dupT) of HAAO
                      Induced Change L-3-Hydroxykynurenine concentration: increase (FC = 1.9)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hereditary methemoglobinemia [ICD-11: 3A92]
                      Details It is reported that mutation (c.483dupT) of HAAO leads to the increase of L-3-hydroxykynurenine levels compared with control group.
               Regulating Pair (2) Experim Info click to show the details of experiment for validating this pair [1]
                      Introduced Variation Mutation (c.558G-A) of HAAO
                      Induced Change L-3-Hydroxykynurenine concentration: increase (FC = 3.4)
                      Summary Introduced Variation         Induced Change 
                      Disease Status Hereditary methemoglobinemia [ICD-11: 3A92]
                      Details It is reported that mutation (c.558G-A) of HAAO leads to the increase of L-3-hydroxykynurenine levels compared with control group.
References
1 NAD Deficiency, Congenital Malformations, and Niacin Supplementation. N Engl J Med. 2017 Aug 10;377(6):544-552.

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