Expert Reviews in Molecular Medicine

 



Review Article

Tryptophan metabolism in the central nervous system: medical implications


Jon P. Ruddick a1 , Andrew K. Evans a1 , David J. Nutt a2 , Stafford L. Lightman a1 , Graham A.W. Rook a3 and Christopher A. Lowry a1c1
a1 Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, UK.
a2 Department of Community Based Medicine, University of Bristol, UK.
a3 Centre for Infectious Diseases and International Health, Windeyer Institute of Medical Sciences, Royal Free and University College Medical School, London, UK.

Article author query
ruddick jp   [Google Scholar] 
evans ak   [Google Scholar] 
nutt dj   [Google Scholar] 
lightman sl   [Google Scholar] 
rook ga   [Google Scholar] 
lowry ca   [Google Scholar] 
 

Abstract

The metabolism of the amino acid L-tryptophan is a highly regulated physiological process leading to the generation of several neuroactive compounds within the central nervous system. These include the aminergic neurotransmitter serotonin (5-hydroxytryptamine, 5-HT), products of the kynurenine pathway of tryptophan metabolism (including 3-hydroxykynurenine, 3-hydroxyanthranilic acid, quinolinic acid and kynurenic acid), the neurohormone melatonin, several neuroactive kynuramine metabolites of melatonin, and the trace amine tryptamine. The integral role of central serotonergic systems in the modulation of physiology and behaviour has been well documented since the first description of serotonergic neurons in the brain some 40 years ago. However, while the significance of the peripheral kynurenine pathway of tryptophan metabolism has also been recognised for several decades, it has only recently been appreciated that the synthesis of kynurenines within the central nervous system has important consequences for physiology and behaviour. Altered kynurenine metabolism has been implicated in the pathophysiology of conditions such as acquired immunodeficiency syndrome (AIDS)-related dementia, Huntington's disease and Alzheimer's disease. In this review we discuss the molecular mechanisms involved in regulating the metabolism of tryptophan and consider the medical implications associated with dysregulation of both serotonergic and kynurenine pathways of tryptophan metabolism.


Correspondence:
c1 Corresponding author: Christopher A. Lowry, Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, UK. Tel: +44 (0)117 331 3119; Fax: +44 (0)117 331 3120; E-mail: c.a.lowry@bristol.ac.uk