International Journal of Tryptophan Research最新文献

{"title":"The Role of the Kynurenine/AhR Pathway in Diseases Related to Metabolism and Cancer.","authors":"Amir Shadboorestan,&nbsp;Meriem Koual,&nbsp;Julien Dairou,&nbsp;Xavier Coumoul","doi":"10.1177/11786469231185102","DOIUrl":"10.1177/11786469231185102","url":null,"abstract":"<p><p>The Aryl hydrocarbon receptor (AhR) is a xenobiotic and endobiotic receptor, which regulates many cellular processes from contaminant metabolism to immunomodulation. Consequently, it is also involved in pathophysiological pathways and now represents a potential therapeutical target. In this review, we will highlight the ancestral function of the protein together with an illustration of its ligand's battery, emphasizing the different responses triggered by these high diverse molecules. Among them, several members of the kynurenine pathway (one key process of tryptophan catabolism) are AhR agonists and are subsequently involved in regulatory functions. We will finally display the interplay between Tryptophan (Trp) catabolism and dysregulation in metabolic pathways drawing hypothesis on the involvement of the AhR pathway in these cancer-related processes.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"16 ","pages":"11786469231185102"},"PeriodicalIF":4.4,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f2/17/10.1177_11786469231185102.PMC10503295.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10286050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endogenous Tryptophan-Derived Ah Receptor Ligands are Dissociated from CYP1A1/1B1-Dependent Negative-Feedback.","authors":"Fangcong Dong,&nbsp;Andrew J Annalora,&nbsp;Iain A Murray,&nbsp;Yuan Tian,&nbsp;Craig B Marcus,&nbsp;Andrew D Patterson,&nbsp;Gary H Perdew","doi":"10.1177/11786469231182508","DOIUrl":"10.1177/11786469231182508","url":null,"abstract":"<p><p>The aryl hydrocarbon receptor (AHR) exerts major roles in xenobiotic metabolism, and in immune and barrier tissue homeostasis. How AHR activity is regulated by the availability of endogenous ligands is poorly understood. Potent AHR ligands have been shown to exhibit a negative feedback loop through induction of CYP1A1, leading to metabolism of the ligand. Our recent study identified and quantified 6 tryptophan metabolites (eg, indole-3-propionic acid, and indole-3-acetic acid) in mouse and human serum, generated by the host and gut microbiome, that are present in sufficient concentrations to individually activate the AHR. Here, these metabolites are not significantly metabolized by CYP1A1/1B1 in an in vitro metabolism assay. In contrast, CYP1A1/1B metabolizes the potent endogenous AHR ligand 6-formylindolo[3,2b]carbazole. Furthermore, molecular modeling of these 6 AHR activating tryptophan metabolites within the active site of CYP1A1/1B1 reveal metabolically unfavorable docking profiles with regard to orientation with the catalytic heme center. In contrast, docking studies confirmed that 6-formylindolo[3,2b]carbazole would be a potent substrate. The lack of CYP1A1 expression in mice fails to influence serum levels of the tryptophan metabolites examined. In addition, marked induction of CYP1A1 by PCB126 exposure in mice failed to alter the serum concentrations of these tryptophan metabolites. These results suggest that certain circulating tryptophan metabolites are not susceptible to an AHR negative feedback loop and are likely important factors that mediate constitutive but low level systemic human AHR activity.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"16 ","pages":"11786469231182508"},"PeriodicalIF":4.4,"publicationDate":"2023-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/db/b9/10.1177_11786469231182508.PMC10331327.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10664912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determination of Picolinic Acid by HPLC Coupled With Postcolumn Photo Irradiation Using Zinc Acetate as a Fluorescent Derivatization Reagent.","authors":"Ken-Ichi Mawatari, Yuika Tanikawa, Makoto Yasuda, Tomoko Fukuuchi, Noriko Yamaoka, Kiyoko Kaneko, Kazuya Nakagomi, Naoto Oku","doi":"10.1177/11786469221146596","DOIUrl":"10.1177/11786469221146596","url":null,"abstract":"<p><p>For the fluorometric determination of picolinic acid in human serum, HPLC-postcolumn UV irradiation using zinc acetate has been developed. Picolinic acid in serum sample was separated on a Capcell Pak C18. The mobile phase consisted of 0.1 mol/L sodium phosphate solution (adjusted to pH 3.0) containing 3.0 mmol/L zinc acetate and 3.5 mmol/L trimethylamine, and delivered at a flow rate of 0.8 mL/minutes. In order to stabilize the retention time (6.5 minutes), a back pressure tube (0.4 m × 0.13 mm i.d.) was attached after the photoreaction tube. Column effluent was irradiated with ultraviolet light to produce fluorescence, excitation wavelength of 336 nm and emission wavelength of 448 nm. The calibration graph for picolinic acid showed linearity when the amount was in the range of 0.89 to 455 pmol, and the detection limit (S/N = 3) was determined to be 0.30 pmol. The pretreatment of serum sample consisted of deproteinized by perchloric acid, potassium hydroxide, and mobile phase. The mean recovery of picolinic acid from serum was 99.0%. Using this procedure, the concentration of picolinic acid in serum of a healthy subject was determined.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"16 ","pages":"11786469221146596"},"PeriodicalIF":2.7,"publicationDate":"2023-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fc/5c/10.1177_11786469221146596.PMC10159237.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10297842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon-gamma Mediated Metabolic Pathways in Hospitalized Patients During Acute and Reconvalescent COVID-19.","authors":"Mario Gietl,&nbsp;Francesco Burkert,&nbsp;Stefanie Seiwald,&nbsp;Anna Böhm,&nbsp;Stefanie Hofer,&nbsp;Johanna M Gostner,&nbsp;Talia Piater,&nbsp;Simon Geisler,&nbsp;Guenter Weiss,&nbsp;Judith Loeffler-Ragg,&nbsp;Thomas Sonnweber,&nbsp;Ivan Tancevski,&nbsp;Alex Pizzini,&nbsp;Sabina Sahanic,&nbsp;Dietmar Fuchs,&nbsp;Rosa Bellmann-Weiler,&nbsp;Katharina Kurz","doi":"10.1177/11786469231154244","DOIUrl":"https://doi.org/10.1177/11786469231154244","url":null,"abstract":"<p><strong>Background: </strong>Fatigue, sleep disturbance, and neurological symptoms during and after COVID-19 are common and might be associated with inflammation-induced changes in tryptophan (Trp) and phenylalanine (Phe) metabolism.</p><p><strong>Aim: </strong>This pilot study investigated interferon gamma inducible biochemical pathways (namely Trp catabolism, neopterin, tyrosine [Tyr], and nitrite formation) during acute COVID-19 and reconvalescence.</p><p><strong>Patients and methods: </strong>Thirty one patients with moderate to severe COVID-19 admitted to the University Hospital of Innsbruck in early 2020 (March-May) were followed up. Neurotransmitter precursors Trp, Phe, Tyr as well as kynurenine (Kyn), neopterin, nitrite, and routine laboratory parameters were analyzed during acute infection and at a follow-up (FU) 60 days thereafter. Clinical symptoms of patients (neurological symptoms, fatigue, sleep disturbance) were recorded and associations with concentrations of laboratory parameters investigated.</p><p><strong>Results and conclusion: </strong>Almost half of the patients suffered from neurological symptoms (48.4%), the majority of patients experienced sleep difficulties (56.7%) during acute COVID-19. Fatigue was present in nearly all patients. C-reactive protein (CRP), interleukin-6 (IL-6), neopterin, Kyn, Phe concentrations were significantly increased, and Trp levels depleted during acute COVID-19. Patients with sleep impairment and neurological symptoms during acute illness presented with increased CRP and IL-6 concentrations, Trp levels were lower in patients with sleep disturbance. In general, inflammatory markers declined during reconvalescence. A high percentage of patients suffered from persistent symptoms at FU (neurological symptoms: 17.2%, fatigue: 51.7%, sleeping disturbance: 34.5%) and had higher CRP concentrations. Nitrite and Phe levels were lower in patients with sleeping difficulties at FU and Kyn/Trp ratio, as indicator of IDO activity, was significantly lower in patients with neurological symptoms compared to patients without them at FU. In summary, inflammation induced alterations of amino acid metabolism might be related to acute and persisting symptoms of COVID-19.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"16 ","pages":"11786469231154244"},"PeriodicalIF":4.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10076985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9337166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of Indoleamine 2,3-Dioxygenase 1 During Inflammatory Bowel Disease Activity in Humans and Mice.","authors":"Elisa Proietti,&nbsp;Renske W M Pauwels,&nbsp;Annemarie C de Vries,&nbsp;Elena Orecchini,&nbsp;Claudia Volpi,&nbsp;Ciriana Orabona,&nbsp;Maikel P Peppelenbosch,&nbsp;Gwenny M Fuhler,&nbsp;Giada Mondanelli","doi":"10.1177/11786469231153109","DOIUrl":"https://doi.org/10.1177/11786469231153109","url":null,"abstract":"<p><strong>Background and aims: </strong>Indoleamine 2,3 dioxygenase-1 (IDO1), a key enzyme in tryptophan metabolism, is strongly up-regulated both in human inflammatory bowel disease (IBD) and animal models of colitis, however its role in the pathogenesis is still controversial. In this study, we investigated IDO1 expression and activity in a mouse model of DSS-induced chronic colitis as well as in colon biopsies and sera from IBD patients.</p><p><strong>Methods: </strong>Chronic colitis was induced in mice through the oral administration of dextran sodium sulfate (DSS), and IDO1 activity was induced by i.p. treatment with N-acetyl serotonin (NAS). IDO1 expression and catalytic activity (measured as Kyn/Trp ratio) was evaluated in sera and tissue samples collected from mice and 93 IBD patients under immunotherapy with Vedolizumab (VDZ) or Ustekinumab (UST).</p><p><strong>Results: </strong>Strong up-regulation of IDO1 was found in colons of mice with acute colitis, which follows disease activity. Enhanced IDO1 activity by NAS treatment protects the intestinal mucosa during the recovery phase of chronic colitis. In IBD patients, IDO1 expression and activity correlate with the severity of mucosal inflammation with inflamed regions showing higher IDO1 expression compared to non-inflamed regions within the same patient. Endoscopic response to VDZ/UST treatment is associated with decreased expression of IDO1.</p><p><strong>Conclusions: </strong>This is the first study demonstrating immunomodulatory activity of IDO1 in a chronic mouse model of DSS-induced colitis. As its expression and catalytic activity correlate with the grade of mucosal inflammation and treatment response, IDO1 could represent a promising biomarker for disease severity and treatment monitoring in IBD.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"16 ","pages":"11786469231153109"},"PeriodicalIF":4.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9926376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10738704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial Indoleamine-2,3-Dioxygenase-1 is not Critically Involved in Regulating Antitumor Immunity in the Central Nervous System.","authors":"A P Abu Hejleh,&nbsp;K Huck,&nbsp;K Jähne,&nbsp;C L Tan,&nbsp;T V Lanz,&nbsp;L Epping,&nbsp;J K Sonner,&nbsp;S G Meuth,&nbsp;A Henneberg,&nbsp;C A Opitz,&nbsp;C Herold-Mende,&nbsp;F Sahm,&nbsp;M Platten,&nbsp;K Sahm","doi":"10.1177/11786469231153111","DOIUrl":"https://doi.org/10.1177/11786469231153111","url":null,"abstract":"<p><p>The vascular niche of malignant gliomas is a key compartment that shapes the immunosuppressive brain tumor microenvironment (TME). The blood-brain-barrier (BBB) consisting of specialized endothelial cells (ECs) and perivascular cells forms a tight anatomical and functional barrier critically controlling transmigration and effector function of immune cells. During neuroinflammation and tumor progression, the metabolism of the essential amino acid tryptophan (Trp) to metabolites such as kynurenine has long been identified as an important metabolic pathway suppressing immune responses. Previous studies have demonstrated that indoleamine-2,3-dioxygenase-1 (IDO1), a key rate-limiting enzyme in tryptophan catabolism, is expressed within the TME of high-grade gliomas. Here, we investigate the role of endothelial IDO1 (eIDO1) expression for brain tumor immunity. Single-cell RNA sequencing data revealed that in human glioma tissue, IDO1 is predominantly expressed by activated ECs showing a JAK/STAT signaling pathway-related CXCL11⁺ gene expression signature. In a syngeneic experimental glioma model, eIDO1 is induced by low-dose tumor irradiation. However, cell type-specific ablation of eIDO1 in experimental gliomas did not alter frequency and phenotype of tumor-infiltrating T cells nor tumor growth. Taken together these data argue against a dominant role of eIDO1 for brain tumor immunity.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"16 ","pages":"11786469231153111"},"PeriodicalIF":4.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d3/09/10.1177_11786469231153111.PMC9926378.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10738702","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Contribution of Circulating Host and Microbial Tryptophan Metabolites Toward Ah Receptor Activation.","authors":"Ethan W Morgan,&nbsp;Fangcong Dong,&nbsp;Andrew J Annalora,&nbsp;Iain A Murray,&nbsp;Trenton Wolfe,&nbsp;Reece Erickson,&nbsp;Krishne Gowda,&nbsp;Shantu G Amin,&nbsp;Kristina S Petersen,&nbsp;Penny M Kris-Etherton,&nbsp;Craig B Marcus,&nbsp;Seth T Walk,&nbsp;Andrew D Patterson,&nbsp;Gary H Perdew","doi":"10.1177/11786469231182510","DOIUrl":"https://doi.org/10.1177/11786469231182510","url":null,"abstract":"<p><p>The aryl hydrocarbon receptor (AHR) is a ligand activated transcription factor that plays an integral role in homeostatic maintenance by regulating cellular functions such as cellular differentiation, metabolism, barrier function, and immune response. An important but poorly understood class of AHR activators are compounds derived from host and bacterial metabolism of tryptophan. The commensal bacteria of the gut microbiome are major producers of tryptophan metabolites known to activate the AHR, while the host also produces AHR activators through tryptophan metabolism. We used targeted mass spectrometry-based metabolite profiling to determine the presence and metabolic source of these metabolites in the sera of conventional mice, germ-free mice, and humans. Surprisingly, sera concentrations of many tryptophan metabolites are comparable between germ-free and conventional mice. Therefore, many major AHR-activating tryptophan metabolites in mouse sera are produced by the host, despite their presence in feces and mouse cecal contents. Here we present an investigation of AHR activation using a complex mixture of tryptophan metabolites to examine the biological relevance of circulating tryptophan metabolites. AHR activation is rarely studied in the context of a mixture at relevant concentrations, as we present here. The AHR activation potentials of individual and pooled metabolites were explored using cell-based assays, while ligand binding competition assays and ligand docking simulations were used to assess the detected metabolites as AHR agonists. The physiological and biomedical relevance of the identified metabolites was investigated in the context of a cell-based model for rheumatoid arthritis. We present data that reframe AHR biology to include the presence of a mixture of ubiquitous tryptophan metabolites, improving our understanding of homeostatic AHR activity and models of AHR-linked diseases.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"16 ","pages":"11786469231182510"},"PeriodicalIF":4.4,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d2/a9/10.1177_11786469231182510.PMC10334013.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10300891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tryptophan and Biogenic Amines in the Differentiation and Quality of Honey.","authors":"Cristine Vanz Borges, Aline Nunes, Vladimir Eliodoro Costa, Ricardo de Oliveira Orsi, Leticia Silva Pereira Basilio, Gean Charles Monteiro, Marcelo Maraschin, Giuseppina Pace Pereira Lima","doi":"10.1177/11786469221102098","DOIUrl":"10.1177/11786469221102098","url":null,"abstract":"<p><p>Honey is a natural product with beneficial properties to health and has different characteristics depending on the region of production and collection, flowering, and climate. The presence of precursor amino acids of- and biogenic amines can be important in metabolomic studies of differentiation and quality of honey. We analyzed 65 honeys from 11 distinct regions of the State of Santa Catarina (Brazil) as to the profile of amino acids and biogenic amines by HPLC. The highest L-tryptophan (Trp), 5-hydroxytryptophan (5-OH-Trp), and tryptamine (Tryp) levels were detected in Cfb climate and harvested in 2019. Although we have found high content of serotonin, dopamine, and L-dopa in Cfb climate, the highest values occurred in honey produced during the summer 2018 and at altitudes above 900 m. Results indicate that the amino acids and biogenic amine levels in honeys are good indicators of origin. These data warrant further investigation on the honey as source of amino acids precursor of serotonin, melatonin, and dopamine, what can guide the choice of food as source of neurotransmitters.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"15 ","pages":"11786469221102098"},"PeriodicalIF":2.7,"publicationDate":"2022-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/95/f1/10.1177_11786469221102098.PMC9152190.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10256470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plasma Kynurenine: A Promising Marker for the Assessment of Renal Functions","authors":"Fatimah Brekdar, M. Khayat, Afraa Zrieki","doi":"10.1177/11786469221102093","DOIUrl":"https://doi.org/10.1177/11786469221102093","url":null,"abstract":"Background: Chronic kidney disease (CKD) is a worldwide issue due to the high prevalence and the serious complications, including death. Kidney functions are routinely evaluated by measuring creatinine levels, which are influenced by many factors (age, sex, diet, race, and body mass). Kynurenine is the first stable metabolite in the kynurenine pathway, which is activated in the course of CKD. Kynurenine levels in plasma can be correlated to kidney functions in CKD patients. We investigated the relationship between kynurenine levels and kidney functions indicators, and the influence of some variables (sex, age, and preexisting hypertension or diabetes) on its levels in CKD patients. Material And Methods: The study included 66 CKD patients in stages 3 to 5 seen at Tishreen University Hospital, and 22 subjects served as control. Kynurenine levels were measured by using a kynurenine ELISA kit (IDK® immundiagnostik). Results: Kynurenine levels were significantly increased with the increase in CKD stage (P < .001), and were correlated with eGFR (r = −.631, P < .001), creatinine levels (r = −.464, P < .001), and urea levels (r = .528, P < .001). Kynurenine plasma levels were not influenced by age, sex, diabetes, and hypertension in CKD patients. Conclusion: Kynurenine is a promising marker for estimating kidney functions, and its relation with kidney functions is not affected by age, sex, and presence of hypertension or diabetes in CKD patients.","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"47 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90621765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Kynurenine Pathway and Polycystic Ovary Syndrome: Inflammation as a Common Denominator","authors":"Filip Jovanovic, A. Sudhakar, N. Knezevic","doi":"10.1177/11786469221099214","DOIUrl":"https://doi.org/10.1177/11786469221099214","url":null,"abstract":"Polycystic ovary syndrome (PCOS) is a complex metabolic disorder commonly seen in females of reproductive age. The pathophysiology of PCOS is multifactorial and includes dysfunction in ovarian steroidogenesis and folliculogenesis, impaired gonadotropin levels, insulin resistance, gut microbiota imbalance, genetic predisposition, and lifestyle preferences. Low-grade inflammatory conditions such as obesity and impaired glucose tolerance are common metabolic disturbances in women with PCOS. A growing body of literature suggests strong evidence rendering PCOS in close proximity with chronic inflammation as documented by high levels of serum white blood cells, C-reactive protein, and various proinflammatory cytokines seen in this condition. Inflammation seems to be the most common metabolic denominator between the kynurenine pathway and PCOS. The association of tryptophan and kynurenine pathway has already been well documented in mood disorders, neurodegenerative diseases, chronic pain conditions, and different inflammatory states. In this manuscript, we describe the influence of sex steroid hormones on different enzymes of the KP; inflammatory nature of PCOS and CRP as a marker of IDO/TDO activity; and the effects of altered gut flora in women with PCOS. This review provides a novel view of the available evidence of tryptophan and downstream metabolites in PCOS in the context of underlying inflammation.","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"40 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85742401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}