Tryptophan metabolites and brain disorders.
Tryptophan is metabolised primarily along the kynurenine pathway, of which two components are now known to have marked effects on neurons in the central nervous system. Quinolinic acid is an agonist at the population of glutamate receptors which are sensitive to N-methyl-D-aspartate (NMDA), and kynurenic acid is an antagonist at several glutamate receptors. Consequently quinolinic acid can act as a neurotoxin while kynurenic acid is neuroprotectant. A third kynurenine, 3-hydroxykynurenine, can generate free radicals and contribute to, or exacerbate, neuronal damage. Changes in the absolute or relative concentrations of these kynurenines have been implicated in a variety of central nervous system disorders such as the AIDS-dementia complex and Huntington's disease, raising the possibility that interference with their actions or synthesis could lead to new forms of pharmacotherapy for these conditions.
Stone
Trevor W
TW
Institute of Biomedical & Life Sciences,Division of Neuroscience & Biomedical Systems, West Medical Building, University of Glasgow, Glasgow, UK. T.W.Stone@bio.gla.ac.uk
Mackay
Gillian M
GM
Forrest
Caroline M
CM
Clark
Catherine J
CJ
Darlington
L Gail
LG
D015526:AIDS Dementia Complex / Q000378:metabolism; D001927:Brain Diseases / Q000378:metabolism*; D002493:Central Nervous System Diseases / Q000378:metabolism; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism; D007737:Kynurenine / Q000031:analogs & derivatives* / Q000378:metabolism; D017378:Quinolinic Acid / Q000378:metabolism; D014364:Tryptophan / Q000378:metabolism*
C005045:3-hydroxykynurenine; D007737:Kynurenine; D014364:Tryptophan; D017378:Quinolinic Acid