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Trimethylamine-N-oxide

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https://www.readbyqxmd.com/read/28218056/regulation-of-the-escherichia-coli-ydhy-t-operon-in-the-presence-of-alternative-electron-acceptors
#1
Naji Al Ibrahim, Jeffrey Green
The Escherichia coli K-12 ydhY-T operon, coding for a predicted oxidoreductase complex, is activated under anaerobic conditions and repressed in the presence of nitrate or nitrite. Anaerobic activation is mediated by the transcription factor FNR and nitrate/nitrite repression is mediated by NarXL and NarQP. In vitro transcription reactions revealed that the DNA upstream of ydhY-T contains sufficient information for RNA polymerase alone to initiate transcription from five locations. FNR severely inhibited synthesis of two of these transcripts (located upstream of, and within, the FNR binding site) and activated the FNR-dependent promoter previously identified in vivo...
February 3, 2017: Microbiology
https://www.readbyqxmd.com/read/28191513/dietary-cholesterol-and-egg-yolk-should-be-avoided-by-patients-at-risk-of-vascular-disease
#2
REVIEW
J David Spence
Recent recommendations that limits to dietary cholesterol be dropped were probably heavily influenced by propaganda from the egg industry. After conviction for false advertising, the industry has spent hundreds of millions of dollars to convince the public, physicians, and policy makers that dietary cholesterol and egg yolk are harmless. However, there are good reasons for longstanding recommendations that dietary cholesterol be limited to <200 mg/ day in persons at risk of vascular disease. It is seldom understood that this essentially means all people in developed countries who expect to attain an advanced age...
April 1, 2016: Journal of Translational Internal Medicine
https://www.readbyqxmd.com/read/28176881/functional-coupling-of-human-microphysiology-systems-intestine-liver-kidney-proximal-tubule-blood-brain-barrier-and-skeletal-muscle
#3
Lawrence Vernetti, Albert Gough, Nicholas Baetz, Sarah Blutt, James R Broughman, Jacquelyn A Brown, Jennifer Foulke-Abel, Nesrin Hasan, Julie In, Edward Kelly, Olga Kovbasnjuk, Jonathan Repper, Nina Senutovitch, Janet Stabb, Catherine Yeung, Nick C Zachos, Mark Donowitz, Mary Estes, Jonathan Himmelfarb, George Truskey, John P Wikswo, D Lansing Taylor
Organ interactions resulting from drug, metabolite or xenobiotic transport between organs are key components of human metabolism that impact therapeutic action and toxic side effects. Preclinical animal testing often fails to predict adverse outcomes arising from sequential, multi-organ metabolism of drugs and xenobiotics. Human microphysiological systems (MPS) can model these interactions and are predicted to dramatically improve the efficiency of the drug development process. In this study, five human MPS models were evaluated for functional coupling, defined as the determination of organ interactions via an in vivo-like sequential, organ-to-organ transfer of media...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28153917/trimethylamine-n-oxide-in-atherogenesis-impairing-endothelial-self-repair-capacity-and-enhancing-monocyte-adhesion
#4
GuoHua Ma, Bing Pan, Yue Chen, CaiXia Guo, MingMing Zhao, LeMin Zheng, BuXing Chen
Several studies have reported a strong association between high plasma level of Trimethylamine N-oxide (TMAO) and atherosclerosis development. However, the exact mechanism underlying this correlation is unknown. In this study, we try to explore the impact of TMAO on endothelial dysfunction. After TMAO treatment, Human umbilical vein endothelial cells (HUVECs) showed significant impairment in cellular proliferation and HUVECs-ECM adhesion compared to control. Likewise, TMAO markedly suppressed HUVECs migration in transwell migration assay and wound healing assay...
February 2, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28149990/trimethylamine-n-oxide-its-hydration-structure-surface-activity-and-biological-function-viewed-by-vibrational-spectroscopy-and-molecular-dynamics-simulations
#5
Tatsuhiko Ohto, Johannes Hunger, Ellen H G Backus, Wataru Mizukami, Mischa Bonn, Yuki Nagata
The osmolyte molecule trimethylamine-N-oxide (TMAO) stabilizes the structure of proteins. As functional proteins are generally found in aqueous solutions, an important aspect of this stabilization is the interaction of TMAO with water. Here, we review, using vibrational spectroscopy and molecular dynamics simulations, recent studies on the structure and dynamics of TMAO with its surrounding water molecules. This article ends with an outlook on the open questions on TMAO-protein and TMAO-urea interactions in aqueous environments...
February 2, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28129384/blood-trimethylamine-n-oxide-originates-from-microbiota-mediated-breakdown-of-phosphatidylcholine-and-absorption-from-small-intestine
#6
Wolfgang Stremmel, Kathrin V Schmidt, Vera Schuhmann, Frank Kratzer, Sven F Garbade, Claus-Dieter Langhans, Gert Fricker, Jürgen G Okun
Elevated serum trimethylamine-N-oxide (TMAO) was previously reported to be associated with an elevated risk for cardiovascular events. TMAO originates from the microbiota-dependent breakdown of food-derived phosphatidylcholine (PC) to trimethylamine (TMA), which is oxidized by hepatic flavin-containing monooxygenases to TMAO. Our aim was to investigate the predominant site of absorption of the bacterial PC-breakdown product TMA. A healthy human proband was exposed to 6.9 g native phosphatidylcholine, either without concomitant treatment or during application with the topical antibiotic rifaximin, or exposed only to 6...
2017: PloS One
https://www.readbyqxmd.com/read/28122782/a-metabolomic-study-of-biomarkers-of-meat-and-fish-intake
#7
William Cheung, Pekka Keski-Rahkonen, Nada Assi, Pietro Ferrari, Heinz Freisling, Sabina Rinaldi, Nadia Slimani, Raul Zamora-Ros, Milena Rundle, Gary Frost, Helena Gibbons, Eibhlin Carr, Lorraine Brennan, Amanda J Cross, Valeria Pala, Salvatore Panico, Carlotta Sacerdote, Domenico Palli, Rosario Tumino, Tilman Kühn, Rudolf Kaaks, Heiner Boeing, Anna Floegel, Francesca Mancini, Marie-Christine Boutron-Ruault, Laura Baglietto, Antonia Trichopoulou, Androniki Naska, Philippos Orfanos, Augustin Scalbert
BACKGROUND: Meat and fish intakes have been associated with various chronic diseases. The use of specific biomarkers may help to assess meat and fish intake and improve subject classification according to the amount and type of meat or fish consumed. OBJECTIVE: A metabolomic approach was applied to search for biomarkers of meat and fish intake in a dietary intervention study and in free-living subjects from the European Prospective Investigation into Cancer and Nutrition (EPIC) study...
January 25, 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28122695/environmental-enteric-dysfunction-is-associated-with-carnitine-deficiency-and-altered-fatty-acid-oxidation
#8
Richard D Semba, Indi Trehan, Ximin Li, Ruin Moaddel, M Isabel Ordiz, Kenneth M Maleta, Klaus Kraemer, Michelle Shardell, Luigi Ferrucci, Mark Manary
BACKGROUND: Environmental enteric dysfunction (EED), a condition characterized by small intestine inflammation and abnormal gut permeability, is widespread in children in developing countries and a major cause of growth failure. The pathophysiology of EED remains poorly understood. METHODS: We measured serum metabolites using liquid chromatography-tandem mass spectrometry in 400 children, aged 12-59months, from rural Malawi. Gut permeability was assessed by the dual-sugar absorption test...
January 18, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28116386/tmao-and-urea-in-the-hydration-shell-of-the-protein-snase
#9
Nikolai Smolin, Vladimir P Voloshin, Alexey V Anikeenko, Alfons Geiger, Roland Winter, Nikolai N Medvedev
We performed all-atom MD simulations of the protein SNase in aqueous solution and in the presence of two major osmolytes, trimethylamine-N-oxide (TMAO) and urea, as cosolvents at various concentrations and compositions and at different pressures and temperatures. The distributions of the cosolvent molecules and their orientation in the surroundings of the protein were analyzed in great detail. The distribution of urea is largely conserved near the protein. It varies little with pressure and temperature, and does practically not depend on the addition of TMAO...
January 24, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28107906/development-of-data-independent-acquisition-workflows-for-metabolomic-analysis-on-a-quadrupole-orbitrap-platform
#10
Juntuo Zhou, Yuhua Li, Xi Chen, Lijun Zhong, Yuxin Yin
Untargeted metabolomic profiling has been widely used in recent years. However, the low reproducibility of the data-dependent acquisition (DDA) strategy presents a major bottleneck that considerably limits the reliability of metabolomic studies in biological and clinical research. The data-independent acquisition (DIA) strategy is proposed to solve the above-mentioned problem, and it is gaining popularity. This paper presents a novel approach for performing metabolomic analysis using an untargeted, liquid chromatography-data independent-mass spectrometry (LC-DIA-MS) strategy on a quadrupole-Orbitrap platform...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28091798/intake-of-up-to-3-eggs-day-increases-hdl-cholesterol-and-plasma-choline-while-plasma-trimethylamine-n-oxide-is-unchanged-in-a-healthy-population
#11
Diana M DiMarco, Amanda Missimer, Ana Gabriela Murillo, Bruno S Lemos, Olga V Malysheva, Marie A Caudill, Christopher N Blesso, Maria Luz Fernandez
Eggs are a source of cholesterol and choline and may impact plasma lipids and trimethylamine-N-oxide (TMAO) concentrations, which are biomarkers for cardiovascular disease (CVD) risk. Therefore, the effects of increasing egg intake (0, 1, 2, and 3 eggs/day) on these and other CVD risk biomarkers were evaluated in a young, healthy population. Thirty-eight subjects [19 men/19 women, 24.1 ± 2.2 years, body mass index (BMI) 24.3 ± 2.5 kg/m(2)] participated in this 14-week crossover intervention. Participants underwent a 2-week washout with no egg consumption, followed by intake of 1, 2, and 3 eggs/day for 4 weeks each...
January 13, 2017: Lipids
https://www.readbyqxmd.com/read/28077467/gut-microbiota-dependent-trimethylamine-n-oxide-in-acute-coronary-syndromes-a-prognostic-marker-for-incident-cardiovascular-events-beyond-traditional-risk-factors
#12
Xinmin S Li, Slayman Obeid, Roland Klingenberg, Baris Gencer, François Mach, Lorenz Räber, Stephan Windecker, Nicolas Rodondi, David Nanchen, Olivier Muller, Melroy X Miranda, Christian M Matter, Yuping Wu, Lin Li, Zeneng Wang, Hassan S Alamri, Valentin Gogonea, Yoon-Mi Chung, W H Wilson Tang, Stanley L Hazen, Thomas F Lüscher
AIMS: Systemic levels of trimethylamine N-oxide (TMAO), a pro-atherogenic and pro-thrombotic metabolite produced from gut microbiota metabolism of dietary trimethylamine (TMA)-containing nutrients such as choline or carnitine, predict incident cardiovascular event risks in stable primary and secondary prevention subjects. However, the prognostic value of TMAO in the setting of acute coronary syndromes (ACS) remains unknown. METHODS AND RESULTS: We investigated the relationship of TMAO levels with incident cardiovascular risks among sequential patients presenting with ACS in two independent cohorts...
January 11, 2017: European Heart Journal
https://www.readbyqxmd.com/read/28077427/serum-trimethylamine-n-oxide-carnitine-choline-and-betaine-in-relation-to-colorectal-cancer-risk-in-the-alpha-tocopherol-and-beta-carotene-study
#13
Kristin A Guertin, Xinmin S Li, Barry I Graubard, Demetrius Albanes, Stephanie J Weinstein, James J Goedert, Zeneng Wang, Stanley L Hazen, Rashmi Sinha
BACKGROUND: TMAO, a choline-derived metabolite produced by gut microbiota, and its biomarker precursors have not been adequately evaluated in relation to colorectal cancer risk. METHODS: We investigated the relationship between serum concentrations of TMAO and its biomarker precursors (choline, carnitine and betaine) and incident colorectal cancer risk in a nested case-control study of male smokers in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study...
January 11, 2017: Cancer Epidemiology, Biomarkers & Prevention
https://www.readbyqxmd.com/read/28072830/protective-effects-of-dexrazoxane-against-doxorubicin-induced-cardiotoxicity-a-metabolomic-study
#14
Yang QuanJun, Yang GenJin, Wan LiLi, Han YongLong, Huo Yan, Li Jie, Huang JinLu, Lu Jin, Gan Run, Guo Cheng
Cardioprotection of dexrazoxane (DZR) against doxorubicin (DOX)-induced cardiotoxicity is contentious and the indicator is controversial. A pairwise comparative metabolomics approach was used to delineate the potential metabolic processes in the present study. Ninety-six BALB/c mice were randomly divided into two supergroups: tumor and control groups. Each supergroup was divided into control, DOX, DZR, and DOX plus DZR treatment groups. DOX treatment resulted in a steady increase in 5-hydroxylysine, 2-hydroxybutyrate, 2-oxoglutarate, 3-hydroxybutyrate, and decrease in glucose, glutamate, cysteine, acetone, methionine, asparate, isoleucine, and glycylproline...
2017: PloS One
https://www.readbyqxmd.com/read/28062632/trimethylamine-n-oxide-and-risk-stratification-after-acute-myocardial-infarction
#15
Toru Suzuki, Liam M Heaney, Donald J L Jones, Leong L Ng
BACKGROUND: Risk stratification in acute myocardial infarction (MI) remains a clinical challenge. Trimethylamine N-oxide (TMAO), a gut-derived metabolite, was investigated for its ability to assist in risk stratification for acute MI hospitalizations. METHODS: TMAO was analyzed in 1079 acute MI patients. Associations with adverse outcome of all-cause mortality or reinfarction (death/MI) for shorter (6-month) and longer (2-year) terms were assessed and compared to other cohort-specific biomarkers...
January 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28056754/gut-microbiota-in-vascular-disease-therapeutic-target
#16
A N Anbazhagan, S Priyamvada, M Priyadarshini
Gut microbiota is increasingly recognized as a powerful regulator of host physiology. Most of effects are mediated through metabolites acting as energy sources, signaling molecules, receptor ligands and substrates for host enzymes. Owing to the meta-stability and high amenability of the gut microbiota to modification by diet and environment, predicting specific gut microbes or its metabolites responsible for different host metabolic states is often confounded. However, through animal models and human studies a direct role of gut microbes in cardiovascular disorders (CVD) has emerged...
January 4, 2017: Current Vascular Pharmacology
https://www.readbyqxmd.com/read/28049038/trimethylamine-n-oxide-impairs-pyruvate-and-fatty-acid-oxidation-in-cardiac-mitochondria
#17
Marina Makrecka-Kuka, Kristine Volska, Unigunde Antone, Reinis Vilskersts, Solveiga Grinberga, Dace Bandere, Edgars Liepinsh, Maija Dambrova
Increased plasma concentration of trimethylamine N-oxide (TMAO), a proatherogenic metabolite, has been linked to adverse cardiovascular outcomes; however, it remains unclear whether TMAO is a biomarker or whether it induces direct detrimental cardiovascular effects. Because altered cardiac energy metabolism and mitochondrial dysfunction play crucial roles in the development of cardiovascular diseases, we hypothesized that increased TMAO concentration may alter mitochondrial energy metabolism. The aim of the present study was to determine the effects of TMAO on cardiac mitochondrial energy metabolism...
February 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28012600/the-gut-blood-barrier-permeability-a-new-marker-in-cardiovascular-and-metabolic-diseases
#18
Marcin Ufnal, Kinga Pham
Recent studies suggest that blood-borne metabolites of gut microbiota, such as trimethylamine N-oxide (TMAO) are involved in the aetiology of cardiovascular diseases and may serve as markers of cardiovascular risk. To enter the bloodstream the microbiota-derived molecules need to pass the gut-blood barrier (GBB). The GBB plays an important role in maintaining organism homeostasis. It is a complex multi-layer system which determines the absorption of nutrients, water and many other substances. The integrity and permeability of the GBB may be impaired in numerous diseases including gastrointestinal, metabolic and cardiovascular diseases...
January 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28012316/the-effect-of-trimethylamine-n-oxide-on-helicobacter-pylori-induced-changes-of-immunoinflammatory-genes-expression-in-gastric-epithelial-cells
#19
Daoyan Wu, Mei Cao, Jingshan Peng, Ningzhe Li, Sijun Yi, Liju Song, Xuege Wang, Mao Zhang, Jian Zhao
Colonization of Helicobacter pylori (H. pylori) induces immune and inflammatory response in gastric mucosa. Trimethylamine N-oxide (TMAO), from diet and metabolite through the action of gut microbiota, has been linked to inflammatory diseases. To investigate the effects of TMAO and H. pylori infection on gene expression in gastric epithelial cells, Human gene chip Affymetrix HTA 2.0 was used in this study. 1312 genes were identified as differentially expressed genes in GES-1 cells with H. pylori and TMAO co-treatment compared to the control...
February 2017: International Immunopharmacology
https://www.readbyqxmd.com/read/27997715/structural-mechanism-for-bacterial-oxidation-of-oceanic-trimethylamine-into-trimethylamine-n-oxide
#20
Chun-Yang Li, Xiu-Lan Chen, Dian Zhang, Peng Wang, Qi Sheng, Ming Peng, Bin-Bin Xie, Qi-Long Qin, Ping-Yi Li, Xi-Ying Zhang, Hai-Nan Su, Xiao-Yan Song, Mei Shi, Bai-Cheng Zhou, Lu-Ying Xun, Yin Chen, Yu-Zhong Zhang
Trimethylamine (TMA) and trimethylamine N-oxide (TMAO) are widespread in the ocean and are important nitrogen source for bacteria. TMA monooxygenase (Tmm), a bacterial flavin-containing monooxygenase (FMO), is found widespread in marine bacteria and is responsible for converting TMA to TMAO. However, the molecular mechanism of TMA oxygenation by Tmm has not been explained. Here, we determined the crystal structures of two reaction intermediates of a marine bacterial Tmm (RnTmm) and elucidated the catalytic mechanism of TMA oxidation by RnTmm...
December 20, 2016: Molecular Microbiology
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