Triptofan ve metabolitleri inflamasyon hastalıklarında biyobelirteç olabilir mi?
Loading...
Files
Date
2024
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
Selçuk Üniversitesi, Sağlık Bilimleri Enstitüsü
Access Rights
info:eu-repo/semantics/openAccess
Abstract
İnflamasyon, patojenler, hasarlı hücreler veya tahriş edici maddeler gibi zararlı uyarıcılara karşı bağışıklık sisteminin karmaşık bir biyolojik tepkisidir. Triptofan, aromatik bir indolilpropiyonik asit ve diyetin temel bir bileşenidir. Protein sentezinde önemli bir rol oynar ve serotonin, melatonin, kinolinik asit, kinurenik asit, triptamin gibi biyolojik olarak aktif bileşiklerin ve ayrıca nikotinamid adenin dinükleotid gibi redoks metabolizma dengesi için önemli olan koenzimlerin öncüsüdür. Toplam Triptofanın %90'ından fazlası, Kinurenin yolağı ile karaciğerde kinureninlere oksitlenmektedir. Triptofan ve onun aşağı akış metabolitlerinin düzeylerini analiz ederek amacımız, Triptofanın biyobelirteç olarak potansiyel rolünü ve Triptofan metabolitlerinin seviyeleri ile hastalık şiddeti arasındaki potansiyel korelasyonları araştırmayı amaçlıyoruz. Çalışmamıza Selçuk Üniversitesi Tıp Fakülte Hastanesi 100 hasta ve 50 sağlıklı kontrol dahil edildi. Çalışmaya alınan hastalardan, Mayıs 2021- Ekim 2021 de serum alınmıştır. Numunelerin kromatografik ayrımı ve analizi; LC-MS/MS API 3200 cihazı kullanılarak pozitif elektrosprey iyonizasyon modunda gerçekleştirilmiştir. Çalışmamızda ölçülen Triptofanın metabolitleri kontrole göre Triptofan, Kinurenin, Triptofan/Kinurenin oranı, Kinurenik asit anlamlılık değer (p<0.001) gösterirken sadece 3-Hidroksikinurenin ve 3-Hidroksiantanilik asit anlamlılık değer (p<0.073, p<0.067 sırasıyla) göstermemiştir. Bununla birlikte Triptofan ve Triptofan/Kinurenin oranı inflamasyon biyobelirteçleri ile negatif korelayson göstermiştir. Diğer tarafta Kinurenin ve Kinurenik asit inflamasyon biyobelirteçleri pozitif korelasyon göstermiştir. Çalışmamızda enfekte ve non-enfekte Gruplar arasında triptofan ve metabolitlerinde anlamlı bir farklılık gözlenmemiştir. Bulgularımız, triptofan metabolitlerinin, beyaz kan hücreleri, C-Reaktif Protein ve Eritrosit sedimantasyon hızı gibi geleneksel parametrelerle karşılaştırıldığında inflamasyonun teşhisinde veya izlenmesinde önemli bir avantaj sunmadığını göstermektedir. Ancak Kinurenin yolu metabolitleri artan fizyolojik ve psikolojik stresin patofizyolojisine katkıda bulunabilir. Triptofan metabolitlerinin tekrarlayan inflamasyondaki ve buna bağlı stres tepkilerindeki rolleri gelecekteki çalışmalar için ilgi alanı sunmaktadır. Enfeksiyöz ve enfeksiyöz olmayan hastalar arasında Kinurenin yolu metabolitlerinde anlamlı bir değer gözlemlemedik. Dolaysıyla Kinurenin yolağının inflamasyon kaynağından bağımsız olarak alterasyona uğramaktadır.
Inflammation is a complex biological response of the immune system to harmful stimuli such as pathogens, damaged cells, or irritants. Tryptophan is an aromatic indolyl-propionic acid and an essential component of the diet. It plays an important role in protein synthesis and is a precursor of biologically active compounds such as Serotonin, Melatonin, Quinolinic acid, Kynurenic acid, Tryptamine, as well as coenzymes important for the redox metabolism balance, such as Nicotinamide Adenine dinucleotide. More than 90% of total Tryptophan is oxidized to Kynurenines in the liver via the Kynurenine pathway. By analyzing the levels of Tryptophan and its downstream metabolites, this study aims to investigate the potential role of Tryptophan as a biomarker and potential correlations between Kynurenines levels and disease severity. This research included 100 patients from Selçuk University Faculty of Medicine Hospital and 50 healthy controls. Serum was collected from the patients included in the study between May and October 2021. Chromatographic separation and analysis of samples; were performed in positive electrospray ionization mode using an LC-MS/MS API 3200 device. The metabolites Tryptophan, Kynurenine, Tryptophan/Kynurenine ratio, Kynurenic acid showed significant values (p<0.001) compared to healthy control, while 3-Hydroxykynurenine and 3- Hydroxy-anthranilic acid didn't show significant values (p<0.073, p<0.067, respectively). However, Tryptophan and Tryptophan/Kynurenine ratio showed significant negative correlation with inflammation biomarkers. In contrast, Kynurenine and Kynurenic acid showed significant positive correlation. No significant difference was observed in Tryptophan metabolites between infected and non-infected groups. Our findings suggest that tryptophan metabolites do not offer a significant advantage in diagnosing or monitoring inflammation compared to traditional parameters such as White blood cells, C-reactive protein and Erythrocyte sedimentation rate. However, Kynurenine pathway metabolites may contribute to the pathophysiology of increased physiological and psychological stress. The roles of tryptophan metabolites in recurrent inflammation and associated stress responses offer an area of interest for future studies. No significant values in Kynurenine pathway metabolites between infectious and non-infectious patients. Therefore, the Kynurenine pathway is altered regardless of the source of inflammation.
Inflammation is a complex biological response of the immune system to harmful stimuli such as pathogens, damaged cells, or irritants. Tryptophan is an aromatic indolyl-propionic acid and an essential component of the diet. It plays an important role in protein synthesis and is a precursor of biologically active compounds such as Serotonin, Melatonin, Quinolinic acid, Kynurenic acid, Tryptamine, as well as coenzymes important for the redox metabolism balance, such as Nicotinamide Adenine dinucleotide. More than 90% of total Tryptophan is oxidized to Kynurenines in the liver via the Kynurenine pathway. By analyzing the levels of Tryptophan and its downstream metabolites, this study aims to investigate the potential role of Tryptophan as a biomarker and potential correlations between Kynurenines levels and disease severity. This research included 100 patients from Selçuk University Faculty of Medicine Hospital and 50 healthy controls. Serum was collected from the patients included in the study between May and October 2021. Chromatographic separation and analysis of samples; were performed in positive electrospray ionization mode using an LC-MS/MS API 3200 device. The metabolites Tryptophan, Kynurenine, Tryptophan/Kynurenine ratio, Kynurenic acid showed significant values (p<0.001) compared to healthy control, while 3-Hydroxykynurenine and 3- Hydroxy-anthranilic acid didn't show significant values (p<0.073, p<0.067, respectively). However, Tryptophan and Tryptophan/Kynurenine ratio showed significant negative correlation with inflammation biomarkers. In contrast, Kynurenine and Kynurenic acid showed significant positive correlation. No significant difference was observed in Tryptophan metabolites between infected and non-infected groups. Our findings suggest that tryptophan metabolites do not offer a significant advantage in diagnosing or monitoring inflammation compared to traditional parameters such as White blood cells, C-reactive protein and Erythrocyte sedimentation rate. However, Kynurenine pathway metabolites may contribute to the pathophysiology of increased physiological and psychological stress. The roles of tryptophan metabolites in recurrent inflammation and associated stress responses offer an area of interest for future studies. No significant values in Kynurenine pathway metabolites between infectious and non-infectious patients. Therefore, the Kynurenine pathway is altered regardless of the source of inflammation.
Description
Keywords
İnflamasyon, Kinurenin Yolağı, LC-MS/MS, Triptofan, Inflammation, Kynurenine Pathway, Tryptophan
Journal or Series
WoS Q Value
Scopus Q Value
Volume
Issue
Citation
Gharab, K. M. K. (2024). Triptofan ve metabolitleri inflamasyon hastalıklarında biyobelirteç olabilir mi? (Doktora Tezi). Selçuk Üniversitesi, Sağlık Bilimleri Enstitüsü, Konya.
