Possibility of Amino Acid Treatment to Prevent the Psychiatric Disorders via Modulation of the Production of Tryptophan Metabolite Kynurenic Acid.

Tsutomu Fukuwatari

doi:10.3390/nu12051403

Abstract

Kynurenic acid, a metabolite of the kynurenine pathway of tryptophan catabolism, acts as an antagonist for both the α7 nicotinic acetylcholine receptor and glycine coagonist sites of the N-methyl-d-aspartic acid receptor at endogenous brain concentrations. Elevation of brain kynurenic acid levels reduces the release of neurotransmitters such as dopamine and glutamate, and kynurenic acid is considered to be involved in psychiatric disorders such as schizophrenia and depression. Thus, the control of kynurenine pathway, especially kynurenic acid production, in the brain is an important target for the improvement of brain function or the effective treatment of brain disorders. Astrocytes uptake kynurenine, the immediate precursor of kynurenic acid, via large neutral amino acid transporters, and metabolize kynurenine to kynurenic acid by kynurenine aminotransferases. The former transport both branched-chain and aromatic amino acids, and the latter have substrate specificity for amino acids and their metabolites. Recent studies have suggested the possibility that amino acids may suppress kynurenic acid production via the blockade of kynurenine transport or via kynurenic acid synthesis reactions. This approach may be useful in the treatment and prevention of neurological and psychiatric diseases associated with elevated kynurenic acid levels.

Highlights

The essential amino acid tryptophan is well known as a precursor of several bioactive compounds such as serotonin and melatonin
This approach may be useful in the treatment and prevention of neurological and psychiatric diseases associated with elevated kynurenic acid levels
More than 90% of tryptophan is metabolized by the kynurenine pathway [1], and this pathway plays a critical role in tryptophan catabolism and coenzyme nicotinamide adenine dinucleotide (NAD+ ) supply (Figure 1)

Summary

Introduction

The essential amino acid tryptophan is well known as a precursor of several bioactive compounds such as serotonin and melatonin. More than 90% of tryptophan is metabolized by the kynurenine pathway [1], and this pathway plays a critical role in tryptophan catabolism and coenzyme nicotinamide adenine dinucleotide (NAD+ ) supply (Figure 1). We briefly review recent advances in KYNA research and further describe the ability of amino acids to modulate. Nutrients 2020, 12, x FOR PEER REVIEW ability of amino acids to modulate KYNA production. (12) adenylyltransferase, NAD enzyme, nicotinamide phosphoribosyltransferase, nicotinamide nicotinic acid (nicotinamide).

Function of Kynurenic Acid in the Brain

Schematic representation of theKYNA: interaction between

Kynurenic Acid Synthesis

Effects of Amino Acids on Kynurenic Acid Production

Findings

Conclusions