International Journal of Tryptophan Research最新文献

{"title":"The Associations Between Cognitive Prognosis and Kynurenines Are Modified by the Apolipoprotein ε4 Allele Variant in Patients With Dementia","authors":"Arne Olav Ervik, Stein-Erik Hafstad Solvang, J. Nordrehaug, P. Ueland, Ø. Midttun, A. Hildre, A. McCann, O. Nygård, D. Aarsland, L. Giil","doi":"10.1177/1178646919885637","DOIUrl":"https://doi.org/10.1177/1178646919885637","url":null,"abstract":"Background: The apolipoprotein E ε4 gene variant (APOEε4) confers considerable risk for dementia and affects neuroinflammation, brain metabolism, and synaptic function. The kynurenine pathway (KP) gives rise to neuroactive metabolites, which have inflammatory, redox, and excitotoxic effects in the brain. Aim: To assess whether the presence of at least one APOEε4 allele modifies the association between kynurenines and the cognitive prognosis. Methods: A total of 152 patients with sera for metabolite measurements and APOE genotype were included from the Dementia Study of Western Norway. The participants had mild Alzheimer disease and Lewy body dementia. Apolipoprotein E ε4 gene variant allele status was classified as one or more ε4 versus any other. Mini-Mental State Examination (MMSE) was measured at baseline and for 5 consecutive years. Mann-Whitney U tests and linear mixed-effects models were used for statistical analysis. Results: There were no significant differences in serum concentrations of tryptophan and kynurenine according to the presence or absence of APOEε4. High serum concentrations of kynurenic acid, quinolinic acid, and picolinic acid, and a higher kynurenine-to-tryptophan ratio, were all associated with more cognitive decline in patients without APOEε4 compared to those with the APOEε4 allele (P-value of the interactions < .05). Conclusions: Kynurenic acid, quinolinic acid, picolinic acid, and the kynurenine-to-tryptophan ratio were associated with a significant increase in cognitive decline when the APOEε4 variant was absent, whereas there was a relatively less decline when the APOEε4 variant was present.","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"24 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85501383","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 Plasma [Kynurenine]/[Tryptophan] Ratio and Indoleamine 2,3-Dioxygenase: Time for Appraisal","authors":"A. Badawy, G. Guillemin","doi":"10.1177/1178646919868978","DOIUrl":"https://doi.org/10.1177/1178646919868978","url":null,"abstract":"The plasma kynurenine to tryptophan ([Kyn]/[Trp]) ratio is frequently used to express or reflect the activity of the extrahepatic Trp-degrading enzyme indoleamine 2,3-dioxygenase (IDO). This ratio is increasingly used instead of measurement of IDO activity, which is often low or undetectable in immune and other cells under basal conditions, but is greatly enhanced after immune activation. The use of this ratio is valid in in vitro studies, eg, in cell cultures or isolated organs, but its ‘blanket’ use in in vivo situations is not, because of modulating factors, such as supply of nutrients; the presence of multiple cell types; complex structural and functional tissue arrangements; the extracellular matrix; and hormonal, cytokine, and paracrine interactions. Determinants other than IDO may therefore be involved in vivo. These are hepatic tryptophan 2,3-dioxygenase (TDO) activity and the flux of plasma-free Trp down the Kyn pathway. In addition, conditions leading to accumulation of Kyn, eg, inhibition of activities of Kyn monooxygenase and kynureninase, could lead to elevation of the aforementioned ratio. In this review, the origin of use of this ratio will be discussed, variations in extent of its elevation will be described, evidence against its indiscriminate use will be presented, and examining determinants other than IDO activity and their correlates will be proposed for future studies.","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"17 1","pages":""},"PeriodicalIF":4.4,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87099579","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":"Nicotinamide's Ups and Downs: Consequences for Fertility, Development, Longevity and Diseases of Poverty and Affluence.","authors":"Adrian C Williams,&nbsp;Lisa J Hill","doi":"10.1177/1178646918802289","DOIUrl":"10.1177/1178646918802289","url":null,"abstract":"<p><p>To further explore the role of dietary nicotinamide in both brain development and diseases, particularly those of ageing. Articles cover neurodegenerative disease and cancer. Also discussed are the effects of nicotinamide, contained in meat and supplements and derived from symbionts, on the major transitions of disease and fertility from ancient times up to the present day. A key role for the tryptophan - NAD 'de novo' and immune tolerance pathway are discussed at length in the context of fertility and longevity and the transitions from immune paresis to Treg-mediated immune tolerance and then finally to intolerance and their associated diseases. <b>Abstract:</b> Nicotinamide in human evolution increased cognitive power in a positive feedback loop originally involving hunting. As the precursor to metabolic master molecule NAD it is, as vitamin B3, vital for health. Paradoxically, a lower dose on a diverse plant then cereal-based diet fuelled population booms from the Mesolithic onwards, by upping immune tolerance of the foetus. Increased tolerance of risky symbionts, whether in the gut or TB, that excrete nicotinamide co-evolved as buffers for when diet was inadequate. High biological fertility, despite disease trade-offs, avoided the extinction of <i>Homo sapiens</i> and heralded the dawn of a conscious, creative, and pro-fertility culture. Nicotinamide equity now would stabilise populations and prevent NAD-based diseases of poverty and affluence.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"11 ","pages":"1178646918802289"},"PeriodicalIF":4.4,"publicationDate":"2018-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646918802289","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36633793","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":"Analysis, Nutrition, and Health Benefits of Tryptophan.","authors":"Mendel Friedman","doi":"10.1177/1178646918802282","DOIUrl":"10.1177/1178646918802282","url":null,"abstract":"<p><p>Tryptophan is an essential plant-derived amino acid that is needed for the in vivo biosynthesis of proteins. After consumption, it is metabolically transformed to bioactive metabolites, including serotonin, melatonin, kynurenine, and the vitamin niacin (nicotinamide). This brief integrated overview surveys and interprets our current knowledge of the reported multiple analytical methods for free and protein-bound tryptophan in pure proteins, protein-containing foods, and in human fluids and tissues, the nutritional significance of l-tryptophan and its isomer d-tryptophan in fortified infant foods and corn tortillas as well the possible function of tryptophan in the diagnosis and mitigation of multiple human diseases. Analytical methods include the use of acid ninhydrin, near-infrared reflectance spectroscopy, colorimetry, basic hydrolysis; acid hydrolysis of <i>S</i>-pyridylethylated proteins, and high-performance liquid and gas chromatography-mass spectrometry. Also covered are the nutritional values of tryptophan-fortified infant formulas and corn-based tortillas, safety of tryptophan for human consumption and the analysis of maize (corn), rice, and soybean plants that have been successfully genetically engineered to produce increasing tryptophan. Dietary tryptophan and its metabolites seem to have the potential to contribute to the therapy of autism, cardiovascular disease, cognitive function, chronic kidney disease, depression, inflammatory bowel disease, multiple sclerosis, sleep, social function, and microbial infections. Tryptophan can also facilitate the diagnosis of certain conditions such as human cataracts, colon neoplasms, renal cell carcinoma, and the prognosis of diabetic nephropathy. The described findings are not only of fundamental scientific interest but also have practical implications for agriculture, food processing, food safety, nutrition, and animal and human health. The collated information and suggested research need will hopefully facilitate and guide further studies needed to optimize the use of free and protein-bound tryptophan and metabolites to help improve animal and human nutrition and health.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"11 ","pages":"1178646918802282"},"PeriodicalIF":4.4,"publicationDate":"2018-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646918802282","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36539918","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":"The Influence of Nicotinamide on Health and Disease in the Central Nervous System.","authors":"Rosemary A Fricker,&nbsp;Emma L Green,&nbsp;Stuart I Jenkins,&nbsp;Síle M Griffin","doi":"10.1177/1178646918776658","DOIUrl":"https://doi.org/10.1177/1178646918776658","url":null,"abstract":"<p><p>Nicotinamide, the amide form of vitamin B₃ (niacin), has long been associated with neuronal development, survival, and function in the central nervous system (CNS), being implicated in both neuronal death and neuroprotection. Here, we summarise a body of research investigating the role of nicotinamide in neuronal health within the CNS, with a focus on studies that have shown a neuroprotective effect. Nicotinamide appears to play a role in protecting neurons from traumatic injury, ischaemia, and stroke, as well as being implicated in 3 key neurodegenerative conditions: Alzheimer's, Parkinson's, and Huntington's diseases. A key factor is the bioavailability of nicotinamide, with low concentrations leading to neurological deficits and dementia and high levels potentially causing neurotoxicity. Finally, nicotinamide's potential mechanisms of action are discussed, including the general maintenance of cellular energy levels and the more specific inhibition of molecules such as the nicotinamide adenine dinucleotide-dependent deacetylase, sirtuin 1 (SIRT1).</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"11 ","pages":"1178646918776658"},"PeriodicalIF":4.4,"publicationDate":"2018-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646918776658","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36173866","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":"Reexamining IFN-γ Stimulation of De Novo NAD+ in Monocyte-Derived Macrophages.","authors":"Peter Moon,&nbsp;Paras Singh Minhas","doi":"10.1177/1178646918773067","DOIUrl":"https://doi.org/10.1177/1178646918773067","url":null,"abstract":"4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage). https://doi.org/10.1177/1178646918773067 International Journal of Tryptophan Research Volume 11: 1 © The Author(s) 2018 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1 78646918773067","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"11 ","pages":"1178646918773067"},"PeriodicalIF":4.4,"publicationDate":"2018-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646918773067","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36127648","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 Tryptophan and Serotonin Metabolism as a Biochemical Basis of the Behavioral Effects of Use and Withdrawal of Androgenic-Anabolic Steroids and Other Image- and Performance-Enhancing Agents.","authors":"Abdulla A-B Badawy","doi":"10.1177/1178646917753422","DOIUrl":"https://doi.org/10.1177/1178646917753422","url":null,"abstract":"<p><p>Modulation of tryptophan (Trp) metabolism may underpin the behavioral effects of androgenic-anabolic steroids (AAS) and associated image and performance enhancers. Euphoria, arousal, and decreased anxiety observed with moderate use and exercise may involve enhanced cerebral serotonin synthesis and function by increased release of albumin-bound Trp and estrogen-mediated liver Trp 2,3-dioxygenase (TDO) inhibition and enhancement of serotonin function. Aggression, anxiety, depression, personality disorders, and psychosis, observed on withdrawal of AAS or with use of large doses, can be caused by decreased serotonin synthesis due to TDO induction on withdrawal, excess Trp inhibiting the 2 enzymes of serotonin synthesis, and increased cerebral levels of neuroactive kynurenines. Exercise and excessive protein and branched-chain amino acid intakes may aggravate the effects of large AAS dosage. The hypothesis is testable in humans and experimental animals by measuring parameters of Trp metabolism and disposition and related metabolic processes.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"11 ","pages":"1178646917753422"},"PeriodicalIF":4.4,"publicationDate":"2018-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646917753422","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35868471","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":"Indoleamine 2,3-Dioxygenase Activity Increases NAD+ Production in IFN-γ-Stimulated Human Primary Mononuclear Cells.","authors":"Ross S Grant","doi":"10.1177/1178646917751636","DOIUrl":"https://doi.org/10.1177/1178646917751636","url":null,"abstract":"<p><p>IFN-γ activation of mononuclear phagocytes significantly increases indoleamine 2,3-dioxygenase (IDO) and flux through the kynurenine pathway (KP). However, the effect of IDO on NAD+ synthesis, the end product of KP metabolism, is unknown. To investigate this, primary human peripheral blood mononuclear cells were cultured up to 10 days and activated with IFN-γ in the presence or absence of a poly(ADP-ribose) polymerase (PARP) inhibitor. Day 10 macrophages had significantly higher NAD+ levels compared with monocytes. IFN-γ activation of macrophages resulted in the highest induction of IDO but decreased intracellular NAD+ concentrations at both 24 and 48 hours. However, IFN-γ activation of both day 6 and day 10 macrophages in the presence of a PARP inhibitor resulted in significantly higher intracellular NAD+ levels at 24 hours. This study provides evidence for the first time that an immune-mediated increase in IDO activity increases NAD+ biosynthesis concomitantly with an increase in NAD+ catabolism in primary human macrophages.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"11 ","pages":"1178646917751636"},"PeriodicalIF":4.4,"publicationDate":"2018-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646917751636","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35745001","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 Metabolism in Patients With Chronic Kidney Disease Secondary to Type 2 Diabetes: Relationship to Inflammatory Markers.","authors":"Subrata Debnath,&nbsp;Chakradhar Velagapudi,&nbsp;Laney Redus,&nbsp;Farook Thameem,&nbsp;Balakuntalam Kasinath,&nbsp;Claudia E Hura,&nbsp;Carlos Lorenzo,&nbsp;Hanna E Abboud,&nbsp;Jason C O'Connor","doi":"10.1177/1178646917694600","DOIUrl":"https://doi.org/10.1177/1178646917694600","url":null,"abstract":"<p><strong>Objective: </strong>Type 2 diabetes (T2D) is the primary case of chronic kidney disease (CKD). Inflammation is associated with metabolic dysregulation in patients with T2D and CKD. Tryptophan (TRP) metabolism may have relevance to the CKD outcomes and associated symptoms. We investigated the relationships of TRP metabolism with inflammatory markers in patients with T2D and CKD.</p><p><strong>Methods: </strong>Data were collected from a well-characterized cohort of type 2 diabetic individuals with all stages of CKD, including patients on hemodialysis. Key TRP metabolites (kynurenine [KYN], kynurenic acid [KYNA], and quinolinic acid [QA]), proinflammatory cytokines (tumor necrosis factor-α [TNF-α] and interleukin-6 [IL-6]), and C-reactive protein were measured in plasma. The KYN/TRP ratio was utilized as a surrogate marker for indoleamine 2,3-dioxygenase 1 (IDO1) enzyme activity.</p><p><strong>Results: </strong>There was a significant inverse association between circulating TRP level and stages of CKD (<i>P</i>< 0.0001). Downstream bioactive TRP metabolites KYN, KYNA, and QA were positively and robustly correlated with the severity of kidney disease (<i>P</i> < 0.0001). In multiple linear regression, neither TNF-α nor IL-6 was independently related to KYN/TRP ratio after adjusting for estimated glomerular filtration rate (eGFR). Only TNF-α was independently related to KYN after taking into account the effect of eGFR.</p><p><strong>Conclusions: </strong>Chronic kidney disease secondary to T2D may be associated with accumulation of toxic TRP metabolites due to both inflammation and impaired kidney function. Future longitudinal studies to determine whether the accumulation of KYN directly contributes to CKD progression and associated symptoms in patients with T2D are warranted.</p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"10 ","pages":"1178646917694600"},"PeriodicalIF":4.4,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1177/1178646917694600","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9546380","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 Metabolism in Rat Liver After Administration of Tryptophan, Kynurenine Metabolites, and Kynureninase Inhibitors.","authors":"Abdulla A-B Badawy,&nbsp;Samina Bano","doi":"10.4137/IJTR.S38190","DOIUrl":"https://doi.org/10.4137/IJTR.S38190","url":null,"abstract":"<p><p>Rat liver tryptophan (Trp), kynurenine pathway metabolites, and enzymes deduced from product/substrate ratios were assessed following acute and/or chronic administration of kynurenic acid (KA), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), Trp, and the kynureni-nase inhibitors benserazide (BSZ) and carbidopa (CBD). KA activated Trp 2,3-dioxygenase (TDO), possibly by increasing liver 3-HAA, but inhibited kynurenine aminotransferase (KAT) and kynureninase activities with 3-HK as substrate. 3-HK inhibited kynureninase activity from 3-HK. 3-HAA stimulated TDO, but inhibited kynureninase activity from K and 3-HK. Trp (50 mg/kg) increased kynurenine metabolite concentrations and KAT from K, and exerted a temporary stimulation of TDO. The kynureninase inhibitors BSZ and CBD also inhibited KAT, but stimulated TDO. BSZ abolished or strongly inhibited the Trp-induced increases in liver Trp and kynurenine metabolites. The potential effects of these changes in conditions of immune activation, schizophrenia, and other disease states are discussed. </p>","PeriodicalId":46603,"journal":{"name":"International Journal of Tryptophan Research","volume":"9 ","pages":"51-65"},"PeriodicalIF":4.4,"publicationDate":"2016-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.4137/IJTR.S38190","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34324502","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}