Transport Systems and Enzymes Involved in the Metamorphosis of Tryptophan into Serotonin

Abstract

Tryptophan (Trp), as the precursor of serotonin, has been introduced in the treatment of depression and isomnia, but its clinical effectiveness must be considered with caution. In this presentation, the different aspects concerning the transport of Trp from the intestine to the brain and its enzymatic conversion into serotonin are discussed. The study of recent literature shows that the discussion about the relative importance of free and total plasma Trp and of the competitive large neutral amino acids for the transport of Trp into the brain continues. On the other hand, mainly animal studies demonstrate numerous regulatory processes, the importance of which has been underestimated until today. These processes concern enzymes like indoleamine-2,3-dioxygenase, cleaving Trp, but also quinoid-dihydropteridine reductase, producing the tetrahydrobiopterin necessary for Trp hydroxylase. It is proposed that the different steps leading from Trp to functionally active 5-HT are considered in a more systemic approach, taking into account that 5-HT synthesis depends on factors like depolarization of the nerve cell, endproduct inhibition, etc. In man, further studies are needed concerning the fate of Trp and competing compounds in the blood, after long-term treatment with Trp. In order to influence enzymatic mechanisms, clinical trials with compounds like tetrahydrobiopterin, acting directly on the enzymatic conversion of Trp into 5-HT, could lend new impulses to research on precursor therapy.

Serotonin transporter genotype and depressive phenotype determination by discriminant analysis of glucose metabolism under acute tryptophan depletion

“…Also important in the function of the serotonergic system, the essential amino acid tryptophan is the precursor for serotonin synthesis (Baumann 1985). Several studies have demonstrated that plasma tryptophan levels are abnormally reduced in depressed subjects as compared to healthy controls (reviewed in (Ressler and Nemeroff 2000)); this effect is not evident in currently remitted subjects with major depressive disorder (RMDD) (Neumeister et al 2004).…”

Simultaneous determination of in vivo hydroxylation of tyrosine and tryptophan in rat striatum by microdialysis-HPLC: relationship between dopamine and serotonin biosynthesis

“…Several lines of evidence have revealed that these two monoamines share the common enzymes for their biosynthesis and metabolism (Baumann, 1985;Cooper etal., 1991), and thereby modulate their functions each other. Sumi et al (1990) demonstrated that the recombinant human aromatic L-amino acid decarboxylase [EC4.1.1.28, AADC-] expressed in COS cells could catalyze decarboxylation of both L-DOPA and 5-HTP.…”