Chemistry and Neurochemistry of the Kynurenine Pathway of Tryptophan Metabolism

摘要

In conclusion it can be seen that the kynurenine pathway of trypto-phan metabolism presents a number of exciting challenges for bio-organic chemists. The enzymes on the pathway catalyse some unusual and interesting transformations. These range from the oxidative cleavage of tryptophan, via the unusual β,γ cleavage catalysed by kynureninase to QPRTase, which apparently catalyses two separate reactions. Mechanistic studies are required in order to understand better the chemistry of these enzyme catalysed reactions. The neurological importance of the pathway and its metabolites is still an issue of some debate. Although it is clear that quinolinic acid levels are elevated in patients with inflammatory brain diseases, it is still to be demonstrated that this is a cause rather than a consequence of the neurological problems. The role of chemists here is to produce potent and specific inhibitors for the enzymes on the pathway, not only as potential therapeutic agents, but also as pharmacological tools to elucidate the importance of the pathway in greater detail. Although some progress has been made in this area there is a great deal of work still to be done.