Endogenous neurotoxins from tryptophan

In most tissues, including brain, a major proportion of the tryptophan which is not used for protein synthesis is metabolised along the kynurenine pathway. Long regarded as the route by which many mammals generate adequate amounts of the essential co-factor nicotinamide adenine dinucleotide, two components of the pathway are now known to have marked effects on neurones. Quinolinic acid is an agonist at the N-methyl-D-aspartate sensitive subtype of glutamate receptors in the brain, while kynurenic acid is an antagonist and, thus, a potential neuroprotectant. A third kynurenine, 3-hydroxykynurenine, is involved in the generation of free radicals which can also damage neurones. Quinolinic acid is increasingly implicated in neurodegenerative disorders, most especially the AIDS-dementia complex and Huntington's disease, while kynurenic acid has become a standard for the identification of glutamate-releasing synapses, and has been used as the parent for several groups of compounds now being developed as drugs for the treatment of epilepsy and stroke. (C) 2000 Elsevier Science Ltd. All rights reserved.