Metabolism of Tryptophan in the Liver: Interference with Decarboxylation of Other Aromatic Amino Acids

Jaroslav Dršata,Eliška Marklová

doi:10.14712/18059694.2019.111

Abstract

Decarboxylation of aromatic amino acid in mammalian tissues is catalyzed by aromatic amino acid decarboxylase (EC. 4.1.1.28, AAD). The enzyme differs in its affinity to individual aromatic amino acids, the best substrates being 3,4-dihydroxyphenylalanine (dopa) and 5-hydroxytroptophan. Surprisingly, AAD is abundant in the liver, where the substrates with rather low affinity to AAD as tryptophan, phenylalanine, and tyrosine are offered to decarboxylation. In the present paper, the possibility of interference of tryptophan with decarboxylation of phenylalanine, tyrosine as well as dopa in the liver was investigated. The AAD activity was measured radiometrically with 1-14C-labeled aromatic amino acid substrates using the rat liver enzyme. The influence of tryptophan on decarboxylation of tyrosine was formally competitive with Ki = 9.2 x 10(-3) M, while the inhibition of decarboxylation of phenylalanine by tryptophan was non-competitive with Ki at 2.75 x 10(-2) M. The effect of tryptophan on decarboxylation of dopa was small and it could not be expressed in terms of inhibition kinetics and inhibition constant. At physiological concentrations of aromatic amino acids in plasma, tryptophan does not seem to have remarkable effects on decarboxylation of phenylalanine, tyrosine, and dopa in the liver.

Highlights

Tryptophan may be metabolized by several different pathways
Neither L-3,4-dihydroxyphenylalanine nor 5-hydroxytryptophan are the compounds that are offered to the liver at higher concentrations, in comparison to more common amino acids as phenylalanine, tyrosine, and tryptophan [7,8]
We have investigated mammalian AAD activity with the substrate L-3,4-dihydroxyphenylalanine under various conditions [9,10]

Summary

Introduction

Tryptophan may be metabolized by several different pathways. The major quantitative breakdown route via kynurenine leads to nicotinic acid and to the synthesis of the NAD coenzyme, other pathways involve indolic compounds. Neither L-3,4-dihydroxyphenylalanine nor 5-hydroxytryptophan are the compounds that are offered to the liver at higher concentrations, in comparison to more common amino acids as phenylalanine, tyrosine, and tryptophan [7,8] For this reason it is rather surprising that the enzyme is abundant in the liver, where creation of its main products under physiological conditions is low, and the significance of the enzyme is not apparent so far. Since the same enzyme catalyzes decarboxylation of a group of amino acids with similar but not identical structures, the effect of various analogues of these compounds have been studied for years The aim of those studies was to affect the synthesis of biologically active decarboxylation products of aromatic amino acids. In the present paper we tried to check, if decarboxylation of phenylalanine, tyrosine or dopa in the liver may be influenced by tryptophan

Materials and methods

Results and discussion

Conclusions