Document Detail


Kynurenic acid and 3-hydroxykynurenine production from D-kynurenine in mice.
MedLine Citation:
PMID:  22498176     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Kynurenic acid (KYNA), an antagonist of the α7 nicotinic acetylcholine receptor and the N-methyl-D-aspartate receptor, and 3-hydroxykynurenine (3-HK), a generator of reactive oxygen species, are neuroactive metabolites of the kynurenine pathway of tryptophan degradation. In the mammalian brain as elsewhere, both compounds derive from a common bioprecursor, L-kynurenine (L-KYN). Recent studies in rats demonstrated that D-kynurenine (D-KYN), a metabolite of the bacterial amino acid D-tryptophan, can also function as a bioprecursor of brain KYNA. We now investigated the conversion of systemically administered D-KYN to KYNA in mice and also explored the possible production of 3-HK in the same animals. Thirty min after an injection of D-KYN or L-KYN (30 mg/kg, i.p.), newly produced KYNA and 3-HK were recovered from plasma, liver, forebrain and cerebellum in all cases. Using a new chiral separation method, 3-HK produced from D-KYN was positively identified as D-3-HK. L-KYN was the more effective precursor of KYNA in all tissues and also exceeded D-KYN as a precursor of brain 3-HK. In contrast, D-KYN was more potent as a precursor of 3-HK in the liver. The production of both KYNA and 3-HK from D-KYN was rapid in all tissues, peaking at 15-30 min following a systemic injection of D-KYN. These results show that biosynthetic routes other than those classically ascribed to L-KYN can account for the synthesis of both KYNA and 3-HK in vivo. This new insight may be of significant physiological or pathological relevance.
Authors:
Xiao-Dan Wang; Francesca M Notarangelo; Ji-Zuo Wang; Robert Schwarcz
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-03-17
Journal Detail:
Title:  Brain research     Volume:  1455     ISSN:  1872-6240     ISO Abbreviation:  Brain Res.     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-04-30     Completed Date:  2013-01-31     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier B.V. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain Chemistry / physiology
Catalysis
Female
Kynurenic Acid / blood,  chemical synthesis,  metabolism*
Kynurenine / analogs & derivatives*,  biosynthesis,  blood,  chemistry,  metabolism*,  physiology
Male
Mice
Mice, Inbred Strains
Stereoisomerism
Tryptophan / administration & dosage
Grant Support
ID/Acronym/Agency:
NS057715/NS/NINDS NIH HHS; R01 NS025296/NS/NINDS NIH HHS; R01 NS025296-23/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
343-65-7/Kynurenine; 484-78-6/3-hydroxykynurenine; 8DUH1N11BX/Tryptophan; H030S2S85J/Kynurenic Acid
Comments/Corrections

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