Expert Reviews in Molecular Medicine: http://www.expertreviews.org/
DOI: 10.1017/S1462399406000068; 31 August 2006
Jon P. Ruddick, Andrew K. Evans, David J. Nutt, Stafford L. Lightman, Graham A.W. Rook and Christopher
A. Lowry (2006) Tryptophan metabolism in the central nervous system: medical implications. Expert Rev.
Mol. Med. Vol. 8, Issue 20, DOI: 10.1017/S1462399406000068

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 ^{a1 c1}

^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.

^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

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.

Full text online (purchase or subscribe through Cambridge Journals Online)

| home | search | glossary | links | sitemap | contact |

Expert Reviews in Molecular Medicine © Cambridge University Press ISSN 1462-3994 (Disclaimer and copyright)
Editorial Office: Centre for Applied Research in Educational Technologies (CARET), 1st Floor, 16 Mill Lane, Cambridge, CB2 1SB, UK. Tel: +44 (0)1223 765 375; Fax: +44(0)1223 765 505; E-mail: ermm@caret.cam.ac.uk