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Trimethylamine-N-oxide

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https://www.readbyqxmd.com/read/29334455/modulating-the-molybdenum-coordination-sphere-of-escherichia-coli-trimethylamine-n-oxide-reductase
#1
Paul Kaufmann, Benjamin R Duffus, Biljana Mitrova, Chantal Iobbi-Nivol, Christian Teutloff, Manfred Nimtz, Lothar Jänsch, Ulla Wollenberger, Silke Leimkühler
The well-studied enterobacterium Escherichia coli present in the human gut is able to reduce TMAO to trimethylamine (TMA) during anaerobic respiration. The TMAO reductase TorA is a monomeric, bis-molybdopterin guanine dinucleotide (bis-MGD) cofactor-containing enzyme belonging to the dimethylsulfoxide (DMSO) reductase family of molybdoenzymes. We report on a system for the in vitro reconstitution of TorA with molybdenum cofactors (Moco) from different sources. Higher TMAO reductase activities for TorA were obtained when using Moco-sources containing a sulfido ligand at the molybdenum atom...
January 15, 2018: Biochemistry
https://www.readbyqxmd.com/read/29333503/the-effect-of-a-vegan-versus-aha-diet-in-coronary-artery-disease-evade-cad-trial-study-design-and-rationale
#2
Binita Shah, Lisa Ganguzza, James Slater, Jonathan D Newman, Nicole Allen, Edward Fisher, John Larigakis, Francisco Ujueta, Eugenia Gianos, Yu Guo, Kathleen Woolf
Background: Multiple studies demonstrate the benefit of a vegan diet on cardiovascular risk factors when compared to no intervention or usual dietary patterns. The aim of this study is to evaluate the effect of a vegan diet versus the American Heart Association (AHA)-recommended diet on inflammatory and glucometabolic profiles in patients with angiographically defined coronary artery disease (CAD). Study Design: This study is a randomized, open label, blinded end-point trial of 100 patients with CAD as defined by ≥50% diameter stenosis in a coronary artery ≥2 mm in diameter on invasive angiography...
December 2017: Contemporary Clinical Trials Communications
https://www.readbyqxmd.com/read/29330424/metagenomic-and-metabolomic-analyses-unveil-dysbiosis-of-gut-microbiota-in-chronic-heart-failure-patients
#3
Xiao Cui, Lei Ye, Jing Li, Ling Jin, Wenjie Wang, Shuangyue Li, Minghui Bao, Shouling Wu, Lifeng Li, Bin Geng, Xin Zhou, Jian Zhang, Jun Cai
Previous studies suggested a possible gut microbiota dysbiosis in chronic heart failure (CHF). However, direct evidence was lacking. In this study, we investigated the composition and metabolic patterns of gut microbiota in CHF patients to provide direct evidence and comprehensive understanding of gut microbiota dysbiosis in CHF. We enrolled 53 CHF patients and 41 controls. Metagenomic analyses of faecal samples and metabolomic analyses of faecal and plasma samples were then performed. We found that the composition of gut microbiota in CHF was significantly different from controls...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29325896/gut-flora-dependent-metabolite-trimethylamine-n-oxide-accelerates-endothelial-cell-senescence-and-vascular-aging-through-oxidative-stress
#4
Yilang Ke, Dang Li, Mingming Zhao, Changjie Liu, Jia Liu, Aiping Zeng, Xiaoyun Shi, Si Cheng, Bing Pan, Lemin Zheng, Huashan Hong
Trimethylamine-N-oxide (TMAO), gut microbiota-dependent metabolites, has been shown to be associated with cardiovascular diseases. However, little is known about the relationship between TMAO and vascular aging. Here, we observed a change in TMAO during the aging process and the effects of TMAO on vascular aging and endothelial cell (EC) senescence. We analyzed age-related plasma levels of TMAO in young adults (18-44 years old), older adults (≥65 years old), and 1-month-old, 3-month-old, 6-month-old and 10-month-old senescence-accelerated mouse prone 8 (SAMP8) and age-matched senescence-accelerated mouse resistance 1 (SAMR1) models...
January 8, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29325094/functional-rescue-of-misfolding-abca3-mutations-by-small-molecular-correctors
#5
Susanna Kinting, Stefanie Höppner, Ulrike Schindlbeck, Maria E Forstner, Jacqueline Harfst, Thomas Wittmann, Matthias Griese
ABCA3, a phospholipid transporter in lung lamellar bodies (LB), is essential for the assembly of pulmonary surfactant and LB biogenesis. Mutations in the ABCA3 gene are an important genetic cause for respiratory distress syndrome in neonates and interstitial lung disease in children and adults, for which there is currently no cure.The aim of this study was to prove that disease causing misfolding ABCA3 mutations can be corrected in vitro and to investigate available options for correction.We stably expressed HA-tagged wild type ABCA3 or variants p...
January 9, 2018: Human Molecular Genetics
https://www.readbyqxmd.com/read/29320696/using-a-fret-library-with-multiple-probe-pairs-to%C3%A2-drive-monte-carlo-simulations-of-%C3%AE-synuclein
#6
John J Ferrie, Conor M Haney, Jimin Yoon, Buyan Pan, Yi-Chih Lin, Zahra Fakhraai, Elizabeth Rhoades, Abhinav Nath, E James Petersson
We describe a strategy for experimentally-constraining computational simulations of intrinsically disordered proteins (IDPs), using α-synuclein, an IDP with a central role in Parkinson's disease pathology, as an example. Previously, data from single-molecule Förster Resonance Energy Transfer (FRET) experiments have been effectively utilized to generate experimentally constrained computational models of IDPs. However, the fluorophores required for single-molecule FRET experiments are not amenable to the study of short-range (<30 Å) interactions...
January 9, 2018: Biophysical Journal
https://www.readbyqxmd.com/read/29316724/biochemical-and-clinical-impact-of-organic-uremic-retention-solutes-a-comprehensive-update
#7
REVIEW
Raymond Vanholder, Anneleen Pletinck, Eva Schepers, Griet Glorieux
In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biological systems of the 11 considered...
January 8, 2018: Toxins
https://www.readbyqxmd.com/read/29315031/osmolyte-adjustments-as-a-pressure-adaptation-in-deep-sea-chondrichthyan-fishes-an-intraspecific-test-in-arctic-skates-amblyraja-hyperborea-along-a-depth-gradient
#8
Paul H Yancey, Ben Speers-Roesch, Sheila Atchinson, James D Reist, Andrew R Majewski, Jason R Treberg
Accumulation of trimethylamine N-oxide (TMAO) by deep-sea animals is proposed to protect proteins against the destabilizing effects of high hydrostatic pressure (the piezolyte hypothesis). Chondrichthyan fishes (sharks, rays, and chimaeras) provide a unique test of this hypothesis because shallow-living species have elevated TMAO levels to counteract the destabilizing effects of high urea levels accumulated for osmoregulation. Limited interspecific studies of chondrichthyans reveal that increasing depth correlates with decreased urea and increased TMAO levels, suggesting a dynamic balance between destabilizing forces on proteins (high urea, hydrostatic pressure) and TMAO to counteract these forces...
March 2018: Physiological and Biochemical Zoology: PBZ
https://www.readbyqxmd.com/read/29313753/compared-to-an-oatmeal-breakfast-two-eggs-day-increased-plasma-carotenoids-and-choline-without-increasing-trimethyl-amine-n-oxide-concentrations
#9
Amanda Missimer, Maria Luz Fernandez, Diana M DiMarco, Gregory H Norris, Christopher N Blesso, Ana Gabriela Murillo, Marcela Vergara-Jimenez, Bruno S Lemos, Isabel Medina-Vera, Olga V Malysheva, Marie A Caudill
BACKGROUND: Habitual consumption of eggs has been hypothesized to positively modify biomarkers of cardiovascular disease risk through proposed antioxidant properties. OBJECTIVES: To examine this relationship, 50 young, healthy men and women were enrolled into a randomized crossover clinical intervention. METHODS: Participants consumed either 2 eggs per day or one packet of oatmeal a day for 4 weeks, followed by a 3-week wash-out and crossed over to the alternate breakfast...
January 9, 2018: Journal of the American College of Nutrition
https://www.readbyqxmd.com/read/29305401/changes-in-gut-microbiota-related-metabolites-and-long-term-successful-weight-loss-in-response-to-weight-loss-diets-the-pounds-lost-trial
#10
Yoriko Heianza, Dianjianyi Sun, Steven R Smith, George A Bray, Frank M Sacks, Lu Qi
OBJECTIVE: Adiposity and the gut microbiota are both related to the risk of type 2 diabetes. We aimed to comprehensively examine how changes induced by a weight-loss diet intervention in gut microbiota-related metabolites, such as trimethylamine N-oxide (TMAO) and its precursors (choline and l-carnitine), were associated with improvements in adiposity and regional fat deposition. RESEARCH DESIGN AND METHODS: This study included 510 overweight and obese individuals who were randomly assigned one of four diets varying in macronutrient intake...
January 5, 2018: Diabetes Care
https://www.readbyqxmd.com/read/29290360/trimethylamine-n-oxide-a-harmful-protective-or-diagnostic-marker-in-lifestyle-diseases
#11
REVIEW
Artur Nowiński, Marcin Ufnal
Diet has been considered a general health determinant for many years. Recent research shows a connection between gut microbiota composition that is shaped by our diet and lifestyle diseases. Several studies point to a positive correlation between elevated plasma trimethylamine N-oxide (TMAO), a gut bacteria metabolite, and an increased risk for cardiovascular diseases, diabetes, and cancer. Therefore, it has been suggested that TMAO is a link between the diet, gut microbiota, and illness. Emerging experimental and clinical evidence shows that TMAO may be involved in the etiology of hypertension, atherosclerosis, coronary artery disease, diabetes, and renal failure...
February 2018: Nutrition
https://www.readbyqxmd.com/read/29290351/red-meat-intake-in-chronic-kidney-disease-patients-two-sides-of-the-coin
#12
REVIEW
Denise Mafra, Natalia A Borges, Ludmila Ferreira Medeiros de Franca Cardozo, Juliana S Anjos, Ana Paula Black, Cristiane Moraes, Peter Bergman, Bengt Lindholm, Peter Stenvinkel
Red meat is an important dietary source of high biological value protein and micronutrients such as vitamins, iron, and zinc that exert many beneficial functions. However, high consumption of animal protein sources, especially red meat, results in an increased intake of saturated fat, cholesterol, iron, and salt, as well as an excessive acid load. Red meat intake may lead to an elevated production of uremic toxins by the gut microbiota, such as trimethylamine n-oxide (TMAO), indoxyl sulfate, and p-cresyl sulfate...
February 2018: Nutrition
https://www.readbyqxmd.com/read/29278490/application-of-a-deep-neural-network-to-metabolomics-studies-and-its-performance-in-determining-important-variables
#13
Yasuhiro Date, Jun Kikuchi
Deep neural networks (DNNs), which are kinds of the machine learning approaches, are powerful tools for analyzing big sets of data derived from biological and environmental systems. However, DNNs are not applicable to metabolomics studies because they have difficulty in identifying contribution factors, e.g., biomarkers, in constructed classification and regression models. In this paper, we describe an improved DNN-based analytical approach that incorporates an importance estimation for each variable using a mean decrease accuracy (MDA) calculation, which is based on a permutation algorithm; this approach is called DNN-MDA...
December 26, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29247650/increased-circulating-trimethylamine-n-oxide-contributes-to-endothelial-dysfunction-in-a-rat-model-of-chronic-kidney-disease
#14
Tiejun Li, Chaojun Gua, Baogang Wu, Yanli Chen
Chronic kidney disease (CKD) is strongly associated with increased cardiovascular risk. Impaired endothelial function, a key initiating step in the pathogenesis of cardiovascular disease, has been reported in patients with CKD, but the mechanisms responsible for endothelial dysfunction in CKD remain elusive. Emerging evidence reveals that trimethylamine-N-oxide (TMAO), a gut microbiota-generated metabolite, is involved in the pathogenesis of many cardiovascular diseases. Circulating TMAO is elevated in CKD...
December 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29240800/effect-of-long-term-dietary-sphingomyelin-supplementation-on-atherosclerosis-in-mice
#15
Rosanna W S Chung, Zeneng Wang, Christina A Bursill, Ben J Wu, Philip J Barter, Kerry-Anne Rye
Sphingomyelin (SM) levels in the circulation correlate positively with atherosclerosis burden. SM is a ubiquitous component of human diets, but it is unclear if dietary SM increases circulating SM levels. Dietary choline increases atherosclerosis by raising circulating trimethylamine N-oxide (TMAO) levels in mice and humans. As SM has a choline head group, we ask in this study if dietary SM accelerates atherosclerotic lesion development by increasing circulating SM and TMAO levels. Three studies were performed: (Study 1) C57BL/6 mice were maintained on a high fat diet with or without SM supplementation for 4 weeks prior to quantification of serum TMAO and SM levels; (Study 2) atherosclerosis was studied in apoE-/- mice after 16 weeks of a high fat diet without or with SM supplementation and (Study 3) apoE-/- mice were maintained on a chow diet for 19 weeks without or with SM supplementation and antibiotic treatment prior to quantification of atherosclerotic lesions and serum TMAO and SM levels...
2017: PloS One
https://www.readbyqxmd.com/read/29236735/hypertension-in-rats-is-associated-with-an-increased-permeability-of-the-colon-to-tma-a-gut-bacteria-metabolite
#16
Kinga Jaworska, Tomasz Huc, Emilia Samborowska, Leszek Dobrowolski, Klaudia Bielinska, Maciej Gawlak, Marcin Ufnal
An increased blood trimethylamine N-oxide (TMAO) has emerged as a marker of cardiovascular mortality, however, the mechanisms of the increase are not clear. We evaluated if hypertension was associated with changes in the colon permeability to trimethylamine (TMA), a TMAO precursor. We did experiments on male, 24-26-week-old normotensive Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR) and SHR treated with enalapril, an antihypertensive drug (SHR-E). To check the colon permeability and liver TMA clearance, blood was collected from the portal vein and hepatic veins confluence, at baseline and after the intracolonic administration of TMA...
2017: PloS One
https://www.readbyqxmd.com/read/29230812/the-gut-microbiota-an-emerging-risk-factor-for-cardiovascular-and-cerebrovascular-disease
#17
REVIEW
Stefanie Ascher, Christoph Reinhardt
Commensal gut microbiota have recently been implicated in cardiovascular disease (CVD) and cerebrovascular disease. Atherosclerotic plaque formation depends on the colonization status of the host. In addition to host nutrition and the related microbiota-dependent metabolic changes, activation of innate immune pathways triggers the development of atherosclerosis and supports arterial thrombosis. Gnotobiotic mouse models have uncovered that activation of Toll-like receptor-2 by gut microbial ligands supports von Willebrand factor-integrin mediated platelet deposition to the site of vascular injury...
December 12, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/29218015/trimethylamine-n-oxide-supplementation-abolishes-the-cardioprotective-effects-of-voluntary-exercise-in-mice-fed-a-western-diet
#18
Hongqi Zhang, Jian Meng, Haiyan Yu
Excessive consumption of western diet (WD) induces obesity, resulting in cardiac dysfunction. Voluntary exercise ameliorates WD-induced obesity, but its effect on cardiac dysfunction remains unclear. Recent evidence suggests that elevated trimethylamine N-oxide (TMAO), a gut microbe-derived metabolite, can impair cardiac function in WD-induced obesity. We hypothesized that cardiac dysfunction in WD-induced obesity would be prevented by voluntary exercise but abolished by TMAO supplementation. Male CD1 mice fed a WD were assigned to sedentary, exercise or exercise with TMAO treatment for 8 weeks...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29214802/tmao-counteracts-urea-denaturation-by-inhibiting-protein-urea-preferential-interaction
#19
Pritam Ganguly, Pablo Boserman, Nico F A van der Vegt, Joan-Emma Shea
Osmolytes are small organic molecules that can modulate the stability and function of cellular proteins by altering the chemical environment of the cell. Some of these osmolytes work in conjunction, via mechanisms that are poorly understood. An example is the naturally-occurring protein-protective osmolyte trimethylamine N-oxide (TMAO) that stabilizes cellular proteins in marine organisms against the detrimental denaturing effects of another naturally occurring osmolyte, urea. From a computational standpoint, our understanding of this counteraction mechanism is hampered by the fact that existing force fields fail to capture the correct balance of TMAO and urea interactions in ternary solutions...
December 7, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29200289/ab-initio-simulations-of-water-dynamics-in-aqueous-tmao-solutions-temperature-and-concentration-effects
#20
Guillaume Stirnemann, Elise Duboué-Dijon, Damien Laage
We use ab initio molecular dynamics simulation to study the effect of hydrophobic groups on the dynamics of water molecules in aqueous solutions of trimethylamine N-oxide (TMAO). We show that hydrophobic groups induce a moderate (<2-fold) slowdown of water reorientation and hydrogen-bond dynamics in dilute solutions, but that this slowdown rapidly increases with solute concentration. In addition, the slowdown factor is found to vary very little with temperature, thus suggesting an entropic origin. All of these results are in quantitative agreement with prior classical molecular dynamics simulations and with the previously suggested excluded-volume model...
December 4, 2017: Journal of Physical Chemistry. B
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