Tracking TRYCAT: A Critical Appraisal of Kynurenine Pathway Quantifications in Blood

Coppens, Violette; Verkerk, Robert; Morrens, Manuel

doi:10.3389/fphar.2022.825948

Cited by 5 publications

(3 citation statements)

References 55 publications

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“…Furthermore, this study did not account for protein binding of the metabolites. Measurements of free metabolites and albumin levels would offer deeper insight into tryptophan metabolism and should be prioritized for future investigations [51,52].…”

Section: Limitationsmentioning

confidence: 99%

Exploring the effect of prolonged fasting on kynurenine pathway metabolites and stress markers in healthy male individuals

Louvrou,

Solianik,

Brazaitis

et al. 2024

Eur J Clin Nutr

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Background/objectives Prolonged fasting triggers a stress response within the human body. Our objective was to investigate the impact of prolonged fasting, in conjunction with stress, on kynurenine pathway metabolites. Subjects/methods Healthy males were divided into fasting group (zero-calorie-restriction) for 6 days (FAST, n = 14), and control group (CON, n = 10). Blood and saliva samples were collected at baseline, Day 2, Day 4, Day 6 during fasting period, and 1 week after resuming regular diet. Plasma levels of kynurenine pathway metabolites were measured using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS). Plasma and salivary samples were analyzed for stress markers. Results A pronounced activation of the kynurenine pathway in individuals on FAST trial was revealed. Concentrations of picolinic acid (PIC), kynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK) were significantly increased, with peak levels observed on Day 6 (P < 0.0001). Conversely, concentrations of tryptophan (TRP) and quinolinic acid (QUIN) decreased (P < 0.0001), while kynurenine (KYN) and nicotinamide (NAM) levels remained stable. Cortisol and noradrenaline concentrations remained unchanged. However, adrenaline levels significantly increased on Day 4 within FAST compared to CON (P = 0.005). Notably, all deviations in kynurenine pathway metabolite levels returned to baseline values upon resuming regular diet following the 6-day fasting regimen, even when weight and BMI parameters were not restored. Conclusions Extended fasting over 6 days induces the kynurenine pathway and has minimal effects on stress markers. Restoration of metabolite concentrations upon regular feeding implies rapid adaptation of the kynurenine pathway synthetic enzymes to maintain homeostasis when faced with perturbations.

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Section: Limitationsmentioning

confidence: 99%

Exploring the effect of prolonged fasting on kynurenine pathway metabolites and stress markers in healthy male individuals

Louvrou,

Solianik,

Brazaitis

et al. 2024

Eur J Clin Nutr

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“…Hepatic and metabolic profiles, especially those associated with IR, are higher in PE than in healthy pregnant women [12]. One of the less studied pathways in the PE is the kynurenine pathway (KP), which degrades 95% of the tryptophan (TRP) to kynurenine (KYN) and either its neurotoxic or neuroprotective immunogenic metabolites [13]. KYN is converted to kynurenic acid (KYNA) by transamination to 3-hydroxykynurenine (3-HK) by hydroxylation.…”

Section: Introductionmentioning

confidence: 99%

Maternal Tryptophan Catabolites and Insulin Resistance Parameters in Preeclampsia

Jasim,

Al-Hakeim,

Zolghadri

et al. 2023

Biomolecules

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Preeclampsia (PE) is a pregnancy-related disorder characterized by high blood pressure and proteinuria in the third trimester. The disease is associated with many metabolic and biochemical changes. There is a need for new biomarkers for diagnosis and follow-up. The present study examined the diagnostic ability of tryptophan catabolites (TRYCATs) and insulin resistance (IR) parameters in women with PE. This case-control study recruited sixty women with preeclampsia and 60 healthy pregnant women as a control group. Serum levels of TRYCATs (tryptophan, kynurenic acid, kynurenine, and 3-hydroxykynurenine) and IR parameters (insulin and glucose) were measured by ELISA and spectrophotometric methods. The results showed that PE women have a significantly lower tryptophan level than healthy pregnant women. However, there was a significant increase in kynurenic acid, kynurenic acid/kynurenine, kynurenine/tryptophan, and 3-hydroxykynurenine levels. PE women also have a state of IR. The correlation study indicated various correlations of IR and TRYCATs with clinical data and between each other, reflecting the role of these parameters in the pathophysiology of PE. The ROC study showed that the presence of IR state, reduced tryptophan, and increased 3-HK predicted PE disease in a suspected woman with moderate sensitivities and specificities. In conclusion, the pathophysiology of PE involves a state of IR and an alteration of the TRYCAT system. These changes should be taken into consideration when PE is diagnosed or treated.

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“…Demonstrating this differentiating power may however prove to be challenging given that (1) different neuropsychiatric illnesses show substantial similarities in the alterations observed in these pathways and (2) these metabolites are also heavily vulnerably to lifestyle factors, as evidenced by modulating effects of BMI, glucose and lipid profiles and other metabolic markers, smoking habits and alimentation status; all of which are themselves affected in neuropsychiatric patients. 7 …”

mentioning

confidence: 99%

LC-MS biomarker diagnostics for neuroinflammatory disorders

Morrens

Coppens

2022

eBioMedicine

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Tracking TRYCAT: A Critical Appraisal of Kynurenine Pathway Quantifications in Blood

Cited by 5 publications

References 55 publications

Exploring the effect of prolonged fasting on kynurenine pathway metabolites and stress markers in healthy male individuals

Exploring the effect of prolonged fasting on kynurenine pathway metabolites and stress markers in healthy male individuals

Maternal Tryptophan Catabolites and Insulin Resistance Parameters in Preeclampsia

LC-MS biomarker diagnostics for neuroinflammatory disorders

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