Abstract
In recent years, tryptophan metabolism via the kynurenine pathway has become one of the most active research areas thanks to its involvement in a variety of physiological processes, especially in conditions associated with immune dysfunction, central nervous system disorders, autoimmunity, infection, diabetes, and cancer. The kynurenine pathway generates several metabolites with immunosuppressive functions or neuroprotective, antioxidant, or toxic properties. An increasing body of work on this topic uncovers a need for reliable analytical methods to help identify and quantify tryptophan metabolites at physiological concentrations in biological samples of different origins. Recent methodological advances in the fabrication and application of electrochemical sensors promise a rise in the future generation of novel analytical systems. This work summarizes current knowledge and provides important suggestions with respect to direct electrochemical determinations of kynurenine pathway metabolites (kynurenines) in complex biological matrices. Measurement challenges, limitations, and future opportunities of electroanalytical methods to advance study of the implementation of kynurenines in disease conditions are discussed.
Highlights
The kynurenine pathway (KP) is the major catabolic route of the essential amino acid, tryptophan (Trp), which generates variety of bioactive metabolites and an important enzyme cofactor, NAD+ (Figure 1).The activity of one of three catabolic enzymes, tryptophan 2,3-dioxygenase (TDO)—expressed in the liver—and two isoforms of indoleamine 2,3-dioxygenase (IDO1 and IDO2)—expressed in various cell types—leads to KP activation in different tissues [1,2]
The process is initiated by activity of IDO1 enzyme and might take place in different cells of the human body like macrophages, dendritic, and tumor cells [3,4].KP starts from the generation of formylkynurenine, which is rapidly converted to kynurenine (Kyn)—the precursor for other catabolites including 3-hydroxykynurenine (3HKyn), kynurenic acid (Kyna), 3-hydroxyanthranilic acid (3HAA), anthranilic acid (AA), xanthurenic acid (XA), and quinolinic acid(QA) [5]
The superiority of fluorometric detection over UV has been reported for 3HAA and AA [38].The results collected in Table 3 suggest that Fluorescence detectors (FLDs) is improper for 3HKyn and QA detection
Summary
The kynurenine pathway (KP) is the major catabolic route of the essential amino acid, tryptophan (Trp), which generates variety of bioactive metabolites (derived from kynurenine) and an important enzyme cofactor, NAD+ (Figure 1).The activity of one of three catabolic enzymes, tryptophan 2,3-dioxygenase (TDO)—expressed in the liver—and two isoforms of indoleamine 2,3-dioxygenase (IDO1 and IDO2)—expressed in various cell types—leads to KP activation in different tissues [1,2]. Beginning in the year 2000, the number of reports utilizing this approach decreased drastically (Table 1).liquid chromatography (LC) employing detection modalities like UV absorbance, fluorescence, and mass spectrometry (MS) has attracted considerable interest for studying Trp metabolism [33].In particular, expanding evidence suggests the LC-MS-based method to be the analytical gold standard for the monitoring and determination of KP metabolites in body fluids, tissues, and cultured cells. Single reports regarding the development and application of electrochemical sensors for KP metabolites quantification in biological samples without chromatographic separation began to appear (Table 1). It seems that a new era of KP research has been initiated. We present future perspectives of using electrochemical sensors in determinations of KP metabolites
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
