A review of chromatographic methods for bioactive tryptophan metabolites, kynurenine, kynurenic acid, quinolinic acid, and others, in biological fluids

Abstract

Kynurenine (KYN) is synthesized from an essential amino acid, tryptophan, by tryptophan 2,3-dioxygenase or indoleamine 2,3-dioxygenase via N-formyl-KYN in vivo.Subsequently, KYN acts as a precursor of some neuroactive metabolites such as kynurenic acid, quinolinic acid, and an important enzyme co-factor, nicotine adenine dinucleotide. These metabolites of tryptophan are a part of the 'kynurenine pathway.' In addition, KYN functions as an endogenous ligand for the aryl hydrocarbon receptor, which acts as a transcription factor. The levels of tryptophan metabolites are important for the assessment of the stage of neurological disorders, and therefore have garnered significant interest for clinical diagnosis. In this review, the detection of kynurenine, kynurenic acid, quinolinic acid, and other tryptophan metabolites performed via chromatographic methods such as HPLC using UV absorbance, fluorescence, and chromatographic-mass spectrometric detection is summarized.

Samarium-Based Turn-Off Fluorescence Sensor for Sensitive and Selective Detection of Quinolinic Acid in Human Urine and Serum

“…By comparison, though its LOD is not as good as those nM levels, the fluorescent Sm-MOF sensor is more stable than the electrochemical and biosensors. Its application conditions are much simpler than those enzymic sensors. ,, With the sensitive fluorescence response in water, urine, and serum, low LOD and relatively wide linear range indicate that the water-stable Sm-MOF can be applied as a turn-off fluorescence sensor to detect QA, which provides an early warning for many diseases.…”

“…Therefore, new detection methods for QA are urgently required to improve screening efficiency. Up to date, the QA detection methods cover gas chromatography (GC), , liquid chromatography (LC), gas chromatography-mass spectrometry (GC-MS), high-pressure and capillary zone electrophoresis, and electrochemical assays . GC-MS is the most reported method for QA determination.…”

To elucidate the mechanism of “Scrophulariae Radix–Fritillaria” in goiter by integrated metabolomics and serum pharmaco-chemistry

“…It is metabolized by tryptophan hydroxylase and aromatic amino acid decarboxylase in the 5-HT pathway. In the kynurenine pathway, tryptophan is metabolized by 2,3-dioxygenase and indoleamine 2,3-dioxygenase to kynurenine (Biswas et al, 2022;Zhen et al, 2022), which is eventually broken down into niacin, quinoline, and xanthurenic acid (Fukushima et al, 2022). In this study, the level of xanthurenic acid was lower and those of quinoline-4,8-diol and 4-(2-aminophenyl)-2,4-dioxobutanoic acid were higher in the urine of goiter rats compared to the controls, which may be related to abnormal kynurenine metabolism.…”

Functionalized 2D Germanene and Its Derivatives for Electrochemical Detection of Gut-Derived Metabolites in Human Serum

“…These neurological disorders have affected more than 1 billion people worldwide and resulted in close to 7 million deaths yearly [3]. Chromatographic techniques and enzyme-linked immunosorbent assays are mostly reported in the literature to determine KA and QA [4,5]. Nevertheless, these approaches are still expensive, time-consuming, involve bulky equipment and technical expertise and they may suffer from poor sensitivity and stability [2,6,7].…”