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https://www.readbyqxmd.com/read/28812671/sulfate-radicals-enable-a-non-enzymatic-krebs-cycle-precursor
#1
Markus A Keller, Domen Kampjut, Stuart A Harrison, Markus Ralser
The evolutionary origins of the Krebs cycle (tricarboxylic acid cycle) are not currently clear. Despite the existence of a simple non-enzymatic Krebs cycle catalyst being dismissed only a few years ago as 'an appeal to magic', citrate and other intermediates have since been discovered on a carbonaceous meteorite and do interconvert non-enzymatically. To identify a metabolism-like non-enzymatic Krebs cycle catalyst, we used combinatorial, quantitative high-throughput metabolomics to systematically screen iron and sulfate compounds in a reaction mixture that orients on the typical components of Archaean sediment...
March 13, 2017: Nature ecology & evolution
https://www.readbyqxmd.com/read/28771732/direct-assessment-of-the-metabolic-origin-of-carbon-atoms-in-glutamate-from-illuminated-leaves-using-13-c-nmr
#2
Cyril Abadie, Jérémy Lothier, Edouard Boex-Fontvieille, Adam Carroll, Guillaume Tcherkez
Glutamate (Glu) is the cornerstone of nitrogen assimilation and photorespiration in illuminated leaves. Despite this crucial role, our knowledge of the flux to Glu de novo synthesis is rather limited. Here, we used isotopic labelling with (13) CO2 and (13) C-NMR analyses to examine the labelling pattern and the appearance of multi-labelled species of Glu molecules to trace the origin of C-atoms found in Glu. We also compared this with (13) C-labelling patterns in Ala and Asp, which reflect citrate (and thus Glu) precursors, that is, pyruvate and oxaloacetate...
August 3, 2017: New Phytologist
https://www.readbyqxmd.com/read/28762682/-use-of-citrate-in-patients-with-nephrolithiasis
#3
REVIEW
Martino Marangella
Citrate is a tricarboxylic acid and an intermediate metabolite of Krebs cycle. It contributes to oxidative metabolism of both kidney and liver. Alkaline sodium or potassium salts have the potential to increase alkaline reserve. In the kidney citrate is completely filtered at the glomerulus, undergoing to 10-40% tubular resorption. Renal insufficiency, even early, metabolic acidosis, potassium depletion induce hypocitraturia. Its importance in nephrolithiasis stems from its ability to form soluble complexes with calcium and to interfere with crystal formation, thus exerting a dual inhibition, thermodynamic and kinetic...
August 1, 2017: Giornale Italiano di Nefrologia: Organo Ufficiale Della Società Italiana di Nefrologia
https://www.readbyqxmd.com/read/28758940/non-targeted-metabolomics-analysis-of-golden-retriever-muscular-dystrophy-affected-muscles-reveals-alterations-in-arginine-and-proline-metabolism-and-elevations-in-glutamic-and-oleic-acid-in-vivo
#4
Muhammad Abdullah, Joe N Kornegay, Aubree Honcoop, Traci L Parry, Cynthia J Balog-Alvarez, Sara K O'Neal, James R Bain, Michael J Muehlbauer, Christopher B Newgard, Cam Patterson, Monte S Willis
BACKGROUND: Like Duchenne muscular dystrophy (DMD), the Golden Retriever Muscular Dystrophy (GRMD) dog model of DMD is characterized by muscle necrosis, progressive paralysis, and pseudohypertrophy in specific skeletal muscles. This severe GRMD phenotype includes moderate atrophy of the biceps femoris (BF) as compared to unaffected normal dogs, while the long digital extensor (LDE), which functions to flex the tibiotarsal joint and serves as a digital extensor, undergoes the most pronounced atrophy...
July 29, 2017: Metabolites
https://www.readbyqxmd.com/read/28744858/d-malate-decreases-renal-content-of-%C3%AE-ketoglutarate-a-driving-force-of-organic-anion-transporters-oat1-and-oat3-resulting-in-inhibited-tubular-secretion-of-phenolsulfonphthalein-in-rats
#5
Yuichi Uwai, Tatsuya Kawasaki, Tomohiro Nabekura
D-Malate inhibits a Krebs cycle enzyme and the tubular transport of α-ketoglutarate, an intermediate of the Krebs cycle and the driving force for rat organic anion transporter 1 (rOAT1) and rOAT3 in the kidney. In this study, we examined effects of D-malate on the rat organic anion transport system. Uptake of 6-carboxyfluorescein by HEK293 cells expressing rOAT1 or rOAT3 was not affected by D-malate and L-malate. Until 60 min after the intravenous injection of phenolsulfonphthalein (PSP), a typical substrate of the renal organic anion transporters, as a bolus to rats, 47...
July 25, 2017: Biopharmaceutics & Drug Disposition
https://www.readbyqxmd.com/read/28720665/targeted-exome-sequencing-of-krebs-cycle-genes-reveals-candidate-cancer-predisposing-mutations-in-pheochromocytomas-and-paragangliomas
#6
Laura Remacha, Iñaki Comino-Méndez, Susan Richter, Laura Contreras, Maria Currás-Freixes, Guillermo Pita, Rocío Letón, Antonio Galarreta, Rafael Torres-Pérez, Emiliano Honrado, Scherezade Jiménez, Lorena Maestre, Sebastian Moran, Manel Esteller, Jorgina Satrústegui, Graeme Eisenhofer, Mercedes Robledo, Alberto Cascon
Purpose: Mutations in Krebs cycle genes are frequently found in patients with pheochromocytomas/paragangliomas. Disruption of SDH, FH or MDH2 enzymatic activities lead to accumulation of specific metabolites, which give rise to epigenetic changes in the genome that cause a characteristic hypermethylated phenotype. Tumors showing this phenotype, but no alterations in the known predisposing genes, could harbor mutations in other Krebs cycle genes. <p>Experimental Design: We used downregulation and methylation of RBP1, as a marker of a hypermethylation phenotype, to select eleven pheochromocytomas and paragangliomas for targeted exome sequencing of a panel of Krebs cycle-related genes...
July 18, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28712602/anaplerotic-therapy-in-propionic-acidemia
#7
Nicola Longo, Leisa B Price, Eduard Gappmaier, Nancy L Cantor, Sharon L Ernst, Carrie Bailey, Marzia Pasquali
BACKGROUND: Propionic acidemia is a rare metabolic disorder caused by a deficiency of propionyl- CoA carboxylase, the enzyme converting propionyl-CoA to methylmalonyl-CoA that subsequently enters the citric acid cycle as succinyl-CoA. Patients with propionic acidemia cannot metabolize propionic acid, which combines with oxaloacetate to form methylcitric acid. This, with the defective supply of succinyl-CoA, may lead to a deficiency in citric acid cycle intermediates. PURPOSE: The objective of this study was to determine whether supplements with glutamine (400mg/kg per day), citrate (7...
July 12, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28710072/circulating-acylcarnitine-profile-in-human-heart-failure-a-surrogate-of-fatty-acid-metabolic-dysregulation-in-mitochondria-and-beyond
#8
Matthieu Ruiz, Francois Labarthe, Annik Fortier, Bertrand Bouchard, Julie Thompson Legault, Virginie Bolduc, Odile Rigal, Jane Chen, Anique Ducharme, Peter A Crawford, Jean-Claude Tardif, Christine Des Rosiers
Heart failure (HF) is associated with metabolic perturbations, particularly of fatty acids (FA), which remain to be better understood in humans. This study aimed at testing the hypothesis that HF patients with reduced ejection fraction, display systemic perturbations in levels of energy-related metabolites, especially those reflecting dysregulation of FA metabolism, namely acylcarnitines (ACs). Circulating metabolites were assessed using mass spectrometry (MS)-based methods in two cohorts. The main cohort consisted of 72 controls and 68 HF patients, exhibiting depressed left ventricular ejection fraction (25...
July 14, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28690604/phenol-is-the-initial-product-formed-during-growth-and-degradation-of-bromobenzene-by-tropical-marine-yeast-yarrowia-lipolytica-ncim-3589-via-an-early-dehalogenation-step
#9
Aakanksha A Vatsal, Smita S Zinjarde, Ameeta RaviKumar
Bromobenzene (BrB), a hydrophobic, recalcitrant organic compound, is listed by the environmental protection agencies as an environmental and marine pollutant having hepatotoxic, mutagenic, teratogenic, and carcinogenic effects. The tropical marine yeast Yarrowia lipolytica 3589 was seen to grow aerobically on BrB and displayed a maximum growth rate (μmax) of 0.04 h(-1). Furthermore, we also observed an increase in cell size and sedimentation velocity for the cells grown on BrB as compared to the glucose grown cells...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28688166/triheptanoin-for-the-treatment-of-brain-energy-deficit-a-14-year-experience
#10
REVIEW
Fanny Mochel
Triheptanoin is an odd-chain triglyceride with anaplerotic properties-that is, replenishing the pool of metabolic intermediates in the Krebs cycle. Unlike even-chain fatty acids metabolized to acetyl-CoA only, triheptanoin can indeed provide both acetyl-CoA and propionyl-CoA, two key carbon sources for the Krebs cycle. Triheptanoin was initially used in patients with long-chain fatty acid oxidation disorders. The first demonstration of the possible benefit of triheptanoin for brain energy deficit came from a patient with pyruvate carboxylase deficiency, a severe metabolic disease that affects anaplerosis in the brain...
July 8, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28685841/krebs-cycle-rewired-for-macrophage-and-dendritic-cell-effector-functions
#11
REVIEW
Dylan Gerard Ryan, Luke A J O'Neill
The Krebs cycle is an amphibolic pathway operating in the mitochondrial matrix of all eukaryotic organisms. In response to proinflammatory stimuli, macrophages and dendritic cells undergo profound metabolic remodelling to support the biosynthetic and bioenergetic requirements of the cell. Recently, it has been discovered that this metabolic shift also involves the rewiring of the Krebs cycle to regulate cellular metabolic flux and the accumulation of Krebs cycle intermediates, notably, citrate, succinate and fumarate...
July 7, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28646338/chemotherapy-induced-gastrointestinal-toxicity-is-associated-with-changes-in-serum-and-urine-metabolome-and-fecal-microbiota-in-male-sprague-dawley-rats
#12
COMPARATIVE STUDY
Richard A Forsgård, Vannina G Marrachelli, Katri Korpela, Rafael Frias, Maria Carmen Collado, Riitta Korpela, Daniel Monleon, Thomas Spillmann, Pia Österlund
PURPOSE: Chemotherapy-induced gastrointestinal toxicity (CIGT) is a complex process that involves multiple pathophysiological mechanisms. We have previously shown that commonly used chemotherapeutics 5-fluorouracil, oxaliplatin, and irinotecan damage the intestinal mucosa and increase intestinal permeability to iohexol. We hypothesized that CIGT is associated with alterations in fecal microbiota and metabolome. Our aim was to characterize these changes and examine how they relate to the severity of CIGT...
August 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28644754/expression-of-enzymes-related-to-glucose-metabolism-in-non-small-cell-lung-cancer-and-prognosis
#13
Alexandra Giatromanolaki, Efthimios Sivridis, Stella Arelaki, Michael I Koukourakis
Purpose/Aim: Cancer cells are addicted to glycolytic anaerobic pathways, in presence or in absence of a functional Krebs' cycle (phenomenon Warburg). This metabolic predilection relies on both extracellular (impaired vascularization and oxygenation) and intracellular (oncogenic activation of genes) causes. MATERIALS AND METHODS: We investigated the expression and prognostic relevance of enzymes involved in the glucose absorption and metabolism, monocarboxylate transporter (MCT) expression, MCT1 and MCT2, pentose pathway (Glucose-6-phospahte dehydrogenase G6PD), glycogene synthesis (glycogene synthase GYS1), glycolysis (Hexokinase HXKII, phosphofructokinase PFK1, fructose biphosphate aldolase), fate of pyruvate (pyruvate dehydrogenase PDH, phosphorylated pPDH, PDH kinase PDK1, lactate dehydrogenase LDH5 and LDH1) and key Kreb's cycle enzymes (citrate synthase CSynth and isocitrate dehydrogenase IDH)...
June 23, 2017: Experimental Lung Research
https://www.readbyqxmd.com/read/28636751/using-experimentation-to-understand-the-10-year-snowshoe-hare-cycle-in-the-boreal-forest-of-north-america
#14
C J Krebs, R Boonstra, S Boutin
Population cycles have long fascinated ecologists from the time of Charles Elton in the 1920s. The discovery of large population fluctuations in undisturbed ecosystems challenged the idea that pristine nature was in a state of balance. The 10-year cycle of snowshoe hares (Lepus americanus Erxleben) across the boreal forests of Canada and Alaska is a classic cycle, recognized by fur traders for more than 300 years. Since the 1930s ecologists have investigated the mechanisms that might cause these cycles. Proposed causal mechanisms have varied from sunspots to food supplies, parasites, diseases, predation, and social behaviour...
June 21, 2017: Journal of Animal Ecology
https://www.readbyqxmd.com/read/28632748/trimetazidine-therapy-for-diabetic-mouse-hearts-subjected-to-ex-vivo-acute-heart-failure
#15
Emilene Breedt, Lydia Lacerda, M Faadiel Essop
Acute heart failure (AHF) is the most common primary diagnosis for hospitalized heart diseases in Africa. As increased fatty acid β-oxidation (FAO) during heart failure triggers detrimental effects on the myocardium, we hypothesized that trimetazidine (TMZ) (partial FAO inhibitor) offers cardioprotection under normal and obese-related diabetic conditions. Hearts were isolated from 12-14-week-old obese male and female diabetic (db/db) mice versus lean non-diabetic littermates (db/+) controls. The Langendorff retrograde isolated heart perfusion system was employed to establish an ex vivo AHF model: a) Stabilization phase-Krebs Henseleit buffer (10 mM glucose) at 100 mmHg (25 min); b) Critical Acute Heart Failure (CAHF) phase-(1...
2017: PloS One
https://www.readbyqxmd.com/read/28630995/krebs-cycle
#16
Veneta Masson
No abstract text is available yet for this article.
June 20, 2017: Annals of Internal Medicine
https://www.readbyqxmd.com/read/28630053/glucose-catabolism-in-liver-tumors-induced-by-c-myc-can-be-sustained-by-various-pkm1-pkm2-ratios-and-pyruvate-kinase-activities
#17
Andrés Méndez-Lucas, Xiaolei Li, Junjie Hu, Li Che, Xinhua Song, Jiaoyuan Jia, Jingxiao Wang, Chencheng Xie, Paul C Driscoll, Darjus F Tschaharganeh, Diego F Calvisi, Mariia Yuneva, Xin Chen
Different pyruvate kinase isoforms are expressed in a tissue-specific manner, with pyruvate kinase M2 (PKM2) suggested to be the predominant isoform in proliferating cells and cancer cells. Because of differential regulation of enzymatic activities, PKM2, but not PKM1, has been thought to favor cell proliferation. However, the role of PKM2 in tumorigenesis has been recently challenged. Here we report that increased glucose catabolism through glycolysis and increased pyruvate kinase activity in c-MYC-driven liver tumors are associated with increased expression of both PKM1 and PKM2 isoforms and decreased expression of the liver-specific isoform of pyruvate kinase, PKL...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28615447/human-retinal-pigment-epithelial-cells-prefer-proline-as-a-nutrient-and-transport-metabolic-intermediates-to-the-retinal-side
#18
Jennifer R Chao, Kaitlen Knight, Abbi L Engel, Connor Jankowski, Yekai Wang, Megan A Manson, Haiwei Gu, Danijel Djukovic, Daniel Raftery, James B Hurley, Jianhai Du
Metabolite transport is a major function of the retinal pigment epithelium (RPE) to support the neural retina. RPE dysfunction plays a significant role in retinal degenerative diseases. We have used mass spectrometry with (13)C tracers to systematically study nutrient consumption and metabolite transport in cultured human fetal RPE. LC/MS-MS detected 120 metabolites in the medium from either the apical or basal side. Surprisingly, more proline is consumed than any other nutrient, including glucose, taurine, lipids, vitamins, or other amino acids...
August 4, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28604247/brucella-central-carbon-metabolism-an-update
#19
T Barbier, A Zúñiga-Ripa, S Moussa, H Plovier, J F Sternon, L Lázaro-Antón, R Conde-Álvarez, X De Bolle, M Iriarte, I Moriyón, J J Letesson
The brucellae are facultative intracellular pathogens causing brucellosis, an important zoonosis. Here, we review the nutritional, genetic, proteomic and transcriptomic studies on Brucella carbon uptake and central metabolism, information that is needed for a better understanding of Brucella virulence. There is no uniform picture across species but the studies suggest primary and/or secondary transporters for unknown carbohydrates, lactate, glycerol phosphate, erythritol, xylose, ribose, glucose and glucose/galactose, and routes for their incorporation to central metabolism, including an erythritol pathway feeding the pentose phosphate cycle...
June 12, 2017: Critical Reviews in Microbiology
https://www.readbyqxmd.com/read/28602540/deficiencies-in-mitochondrial-dynamics-sensitize-caenorhabditis-elegans-to-arsenite-and-other-mitochondrial-toxicants-by-reducing-mitochondrial-adaptability
#20
Anthony L Luz, Tewodros R Godebo, Latasha L Smith, Tess C Leuthner, Laura L Maurer, Joel N Meyer
Mitochondrial fission, fusion, and mitophagy are interlinked processes that regulate mitochondrial shape, number, and size, as well as metabolic activity and stress response. The fundamental importance of these processes is evident in the fact that mutations in fission (DRP1), fusion (MFN2, OPA1), and mitophagy (PINK1, PARK2) genes can cause human disease (collectively >1/10,000). Interestingly, however, the age of onset and severity of clinical manifestations varies greatly between patients with these diseases (even those harboring identical mutations), suggesting a role for environmental factors in the development and progression of certain mitochondrial diseases...
July 15, 2017: Toxicology
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