Tryptophan is an essential amino acid that fulfils two main roles in human nutrition. Firstly, tryptophan can be converted to niacin, a member of the B vitamin family of vitamins and dietary tryptophan is therefore an important source of niacin in some individuals. The pathway involved in the conversion of tryptophan to niacin is called the kynurenine pathway as xanthurenic and kynurenic acid are products of the pathway. However, as niacin can also be derived from the diet, this pathway may not be important if adequate dietary niacin is supplied. Secondly, tryptophan enters the central nervous system through the large neutral amino acid transporter at the blood brain barrier, and from here it is converted into serotonin and melatonin. Tryptophan is therefore an important precursor amino acid for neurotransmitter synthesis. The rate limiting step in the conversion of tryptophan to serotonin is the tyrosine hydroxylase enzyme catalysed step, and the production of serotonin is therefore under the control of this enzyme.
Once in the brain tryptophan can also be converted to a number of excretory products in the indole pathway, including 5-hydroxyindoleacetic acid (5-HIAA), 5-hydroxytryptophol and indoleacetic acid. This pathway is therefore referred to as the indole pathway. Evidence suggests that there is a balance between the metabolism of tryptophan in the kynurenine and indole pathways. It has been suggested for example that a preference for the kynurenine pathway to the detriment of the indole pathway could lead to changes in the breakdown of serotonin, and this may in turn affect brain function. The possibility that changes to serotonin may be related to certain mental disorders may therefore allow inference that abnormal production of tryptophan metabolites is a useful marker of possible serotonin derived mental changes. Researchers have investigated the excretory products of the indole and kynurenine pathways in alcoholics and schizophrenics to see if they may be related to the mental changes seen in these groups.
For alcoholics that have shown evidence of mental deterioration there is evidence that shifts in the metabolism of tryptophan occur. For example1, in nonalcoholics dietary tryptophan was significantly associated with xanthurenic and kynurenic acid but in alcoholics dietary tryptophan was significantly associated with 5-HIAA. Increases in dietary niacin were associated with increases in xanthurenic and kynurenic acid and 5-HIAA in non-alcoholics but only with 5-HIAA in alcoholics. In another study2, significant associations between dietary tryptophan levels and xanthurenic and kynurenic acid were seen in nonschizophrenics, but not in schizophrenics. Niacin intake was associated with xanthurenic and kynurenic acid as well as with 5-HIAA in nonschizophrenics, but not in schizophrenics. These results support the contention that shifts in the metabolism of tryptophan occur in mental disorders including schizophrenia and alcoholism. However, it is unclear if this is a cause or an effect of the metal changes.
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