Document Detail


Enzymatic transamination of D-kynurenine generates kynurenic acid in rat and human brain.
MedLine Citation:
PMID:  22224417     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In the mammalian brain, the α7 nicotinic and NMDA receptor antagonist kynurenic acid is synthesized by irreversible enzymatic transamination of the tryptophan metabolite l-kynurenine. d-kynurenine, too, serves as a bioprecursor of kynurenic acid in several organs including the brain, but the conversion is reportedly catalyzed through oxidative deamination by d-amino acid oxidase. Using brain and liver tissue homogenates from rats and humans, and conventional incubation conditions for kynurenine aminotransferases, we show here that kynurenic acid production from d-kynurenine, like the more efficient kynurenic acid synthesis from l-kynurenine, is blocked by the aminotransferase inhibitor amino-oxyacetic acid. In vivo, focal application of 100 μM d-kynurenine by reverse microdialysis led to a steady rise in extracellular kynurenic acid in the rat striatum, causing a 4-fold elevation after 2 h. Attesting to functional significance, this increase was accompanied by a 36% reduction in extracellular dopamine. Both of these effects were duplicated by perfusion of 2 μM l-kynurenine. Co-infusion of amino-oxyacetic acid (2 mM) significantly attenuated the in vivo effects of d-kynurenine and essentially eliminated the effects of l-kynurenine. Thus, enzymatic transamination accounts in part for kynurenic acid synthesis from d-kynurenine in the brain. These results are discussed with regard to implications for brain physiology and pathology.
Authors:
Veronica Pérez-de la Cruz; Laura Amori; Korrapati V Sathyasaikumar; Xiao-Dan Wang; Francesca M Notarangelo; Hui-Qiu Wu; Robert Schwarcz
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, N.I.H., Extramural     Date:  2012-02-02
Journal Detail:
Title:  Journal of neurochemistry     Volume:  120     ISSN:  1471-4159     ISO Abbreviation:  J. Neurochem.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-03-07     Completed Date:  2012-06-01     Revised Date:  2014-03-19    
Medline Journal Info:
Nlm Unique ID:  2985190R     Medline TA:  J Neurochem     Country:  England    
Other Details:
Languages:  eng     Pagination:  1026-35     Citation Subset:  IM    
Copyright Information:
© 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.
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MeSH Terms
Descriptor/Qualifier:
Animals
Area Under Curve
Brain / drug effects,  enzymology*
Chromatography, High Pressure Liquid
Dopamine / metabolism
Dose-Response Relationship, Drug
Humans
Kynurenic Acid / metabolism*
Kynurenine / metabolism*,  pharmacology
Liver / drug effects,  enzymology*
Male
Microdialysis
Rats
Rats, Sprague-Dawley
Time Factors
Transaminases / metabolism*
Grant Support
ID/Acronym/Agency:
NS057715/NS/NINDS NIH HHS; R01 NS057715/NS/NINDS NIH HHS
Chemical
Reg. No./Substance:
343-65-7/Kynurenine; EC 2.6.1.-/Transaminases; EC 2.6.1.7/kynurenine-oxoglutarate transaminase; H030S2S85J/Kynurenic Acid; VTD58H1Z2X/Dopamine
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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