Functional end products of the essential amino acid tryptophan arise mainly through two distinctive pathways. The major pathway is degradation of tryptophan by oxidation, which fuels the kynurenine pathway (See 00011). The second and quantitatively minor pathway is hydroxylation of tryptophan and its subsequent decarboxylation to the indoleamine 5-hydroxytryptamine (serotonin) and subsequently melatonin. The metabolites of the kynurenine pathway, indicated as kynurenines, include quinolic acid and kynurenic acid. Quinolinic acid is an agonist of the NMDA receptor (see also section on glutamic acid), while kynurenic acid is a nonselective NMDA-receptor antagonist with a high affinity for the glycine site of the NMDA receptor (see also section on glycine), and as such is a blocker of amino acid-modulated excitation of the central nervous system. Imbalance between kynurenic acid and quinolinic acid can lead to excitotoxic neuronal cell death and is believed to play a role in the development of several neurological diseases such as Huntington's chorea and epilepsy. In addition, an immuno-modulatory role is suggested for several metabolites of the kynurenine pathway.

Serotonin is synthesized in the central nervous system and is involved in the regulation of mood and sleep. In addition it is found in high quantities in neurons in the gastrointestinal tract where it is involved in regulation of gut motility. Tryptophan competes with BCAAs for transport across the blood-brain barrier and the ratio between trypto-phan and BCAAs therefore determines the uptake of both (groups of) amino acids by the brain (see section on BCAAs). Since albumin has a strong tryptophan-binding capacity, the plasma albumin concentration is inversely related to the plasma concentration of free tryptophan and as such influences the BCAA to tryp-tophan ratio and hence the brain uptake of both BCAAs and tryptophan. It has been suggested that increased plasma AAAs (tyrosine, phenylalanine, and tryptophan) levels in patients with liver failure are caused by the inability of the liver to degrade these amino acids. The resulting change in the ratio between AAA and BCAA plasma levels has been implied in the pathogenesis of hepatic encephalopa-thy since this may cause marked disturbances in transport of both AAAs and BCAAs across the blood-brain barrier, leading to disturbed release of indoleamines and catecholamines in the brain (see also section on BCAAs). High tryptophan concentrations have been associated with chronic fatigue disorders and hepatic encephalopathy while low tryptophan plasma concentrations have been implicated in the etiology of mood disorders, cognitive impairment, and functional bowel disorders. Melatonin, which is produced in the degradation pathway of serotonin during the dark period of the light-dark cycle, is an important mediator of circa-dian rhythms.

Sleeping Sanctuary

Sleeping Sanctuary

Salvation For The Sleep Deprived The Ultimate Guide To Sleeping, Napping, Resting And  Restoring Your Energy. Of the many things that we do just instinctively and do not give much  of a thought to, sleep is probably the most prominent one. Most of us sleep only because we have to. We sleep because we cannot stay awake all 24 hours in the day.

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