Biological Chemistry - Berezov T. T., Korovkin B. F. 1998

Metabolism of Simple Proteins
Specific Pathways of Metabolism for Certain Amino Acids
Tryptophan Metabolism

Tryptophan is an essential amino acid for humans and animals, as it serves as a precursor to A number of vital BIOLOGICALLY ACTIVE SUBSTANCES, notably serotonin and the nicotinic acid ribonucleotide. In addition, one of its metabolites, indoleacetic acid, exhibits plant growth-stimulating activity (acting as a growth factor). Under physiological conditions, more than 95% of tryptophan is oxidized via the kynurenine pathway and no more than 1% via the serotonin pathway (Fig. 12.7). In the body, serotonin undergoes Oxidative Deamination to yield indoleacetic acid, which is excreted in the urine. The level of this acid in urine is elevated in malignant intestinal carcinoids, where approximately 60% of tryptophan is metabolized via the serotonin pathway. The primary pathway of Tryptophan METABOLISM leads to NAD synthesis, thereby reducing the body's requirement for Vitamin PP. Under the action of the heme-containing enzyme tryptophan 2,3-dioxygenase and in the presence of molecular oxygen, tryptophan is converted into formylkynurenine, which is cleaved by formamidase (formylkynureninase) into formic acid and kynurenine; the latter is then oxidized to 3-hydroxykynurenine. Further transformations of 3-hydroxykynurenine involve the pyridoxal-dependent enzyme kynureninase, which hydrolyzes it into Alanine and 3-hydroxyanthranilic acid. Through a series of intermediates (the formation mechanism of which is not yet fully elucidated), the latter is converted into quinolinic acid, the direct precursor of the nicotinic acid ribonucleotide.

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Fig. 12.7. Metabolic transformations of tryptophan. 458