Tryptophan metabolism in the central nervous system: medical implications

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.

Platelet serotonin concentration and monoamine oxidase type B activity in female patients in early, middle and late phase of Alzheimer's disease

“…The majority of studies have found low tryptophan concentrations in serum (Widner et al 2000), plasma (Fekkes et al 1998) and CSF (Tohgi et al 1992) while other studies showed no alterations in tryptophan concentrations in plasma (Fonteh et al 2007) and brain (Storga et al 1996) in patients with AD. Low plasma tryptophan concentration might be also a consequence of the enhanced tryptophan degradation via the kynuramine pathway (Widner et al 2000), since a dysregulation of both serotonergic and kynuramine pathways of tryptophan metabolism have been associated with pathophysiology of AD (Ruddick et al 2006). In addition, the decline in the cognitive performance was observed after tryptophan depletion in healthy volunteers (Park et al 1994), patients with AD (Porter et al 2000) and patients with mild to moderate AD (Newhouse et al 2002), confirming the role of 5-HT system in behavioral and cognitive changes in AD.…”

Gut Microbiota: The Conductor in the Orchestra of Immune–Neuroendocrine Communication

“…Dysregulation of the kynurenine arm in the tryptophan metabolic pathway, which is observed in many disorders of the brain and the GI tract, 66 involves the catalytic enzyme indoleamine-2,3-dioxygenase, 40 the activity of which is induced by inflammatory mediators and by Clinical Therapeutics 962 Volume 37 Number 5 corticosteroids. 115 These findings suggest that alterations in the production of neuropeptides by dysbiosis would in turn alter the neuroendocrine-immune signaling or act directly on the CNS. The gut microbiota also impacts brain health in several ways.…”

Can Fortified Bifidobacterium with Mycosporin-like Amino Acid be a New Insight for Neurological Disease' s Treatment?

“…Tryptophan is an essential amino acid for neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) products. Impaired tryptophan metabolism has been implicated in the pathophysiology of conditions such as acquired immunodeficiency syndrome-related dementia, Huntington's disease and Alzheimer's disease [36]. The effect of MAAs on central signalling cascades has been investigated in human myelo monocytic THP-1 and THP-1-Blue cells [25].…”