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Alpha-ketoglutarate

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https://www.readbyqxmd.com/read/28813658/ccctc-binding-factor-translates-interleukin-2-and-%C3%AE-ketoglutarate-sensitive-metabolic-changes-in-t%C3%A2-cells-into-context-dependent-gene-programs
#1
Danielle A Chisolm, Daniel Savic, Amanda J Moore, Andre Ballesteros-Tato, Beatriz León, David K Crossman, Cornelis Murre, Richard M Myers, Amy S Weinmann
Despite considerable research connecting cellular metabolism with differentiation decisions, the underlying mechanisms that translate metabolite-sensitive activities into unique gene programs are still unclear. We found that aspects of the interleukin-2 (IL-2)-sensitive effector gene program in CD4(+) and CD8(+) T cells in type 1 conditions (Th1) were regulated by glutamine and alpha-ketoglutarate (αKG)-induced events, in part through changes in DNA and histone methylation states. We further identified a mechanism by which IL-2- and αKG-sensitive metabolic changes regulated the association of CCCTC-binding factor (CTCF) with select genomic sites...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28813209/galangin-a-natural-flavonoid-reduces-mitochondrial-oxidative-damage-in-streptozotocin-induced-diabetic-rats
#2
Amal A Aloud, Chinnadurai Veeramani, Chandramohan Govindasamy, Mohammed A Alsaif, Khalid S Al-Numair
OBJECTIVE: We designed this study to observe the effect of galangin on damaged mitochondria in the liver of diabetic rats. METHODS: Male albino Wistar rats were made diabetic by injecting streptozotocin (STZ) intraperitoneally (40 mg kg(-1) body weight (BW)). Galangin (8 mg kg(-1) BW) or glibenclamide (600 µg kg(-1) BW) was given orally daily once for 45 days to both healthy and diabetic rats. RESULTS: Diabetic rats showed significant (P < 0...
August 16, 2017: Redox Report: Communications in Free Radical Research
https://www.readbyqxmd.com/read/28780590/alpha-ketoglutarate-enhances-freeze-thaw-tolerance-and-prevents-carbohydrate-induced-cell-death-of-the-yeast-saccharomyces-cerevisiae
#3
Maria M Bayliak, Olha V Hrynkiv, Roksolana V Knyhynytska, Volodymyr I Lushchak
Stress resistance and fermentative capability are important quality characteristics of baker's yeast. In the present study, we examined protective effects of exogenous alpha-ketoglutarate (AKG), an intermediate of the tricarboxylic acid cycle and amino acid metabolism, against freeze-thaw and carbohydrate-induced stresses in the yeast Saccharomyces cerevisiae. Growth on AKG-supplemented medium prevented a loss of viability and improved fermentative capacity of yeast cells after freeze-thaw treatment. The cells grown in the presence of AKG had higher levels of amino acids (e...
August 5, 2017: Archives of Microbiology
https://www.readbyqxmd.com/read/28760433/branched-chain-amino-acid-supplementation-in-treatment-of-liver-cirrhosis-updated-views-on-how-to-attenuate-their-harmful-effects-on-cataplerosis-and-ammonia-formation
#4
REVIEW
Milan Holeček
Branched-chain amino acid (BCAA; valine, leucine, and isoleucine) supplementation is common for patients with liver cirrhosis due to decreased levels of BCAA in the blood plasma of these patients, which plays a role in pathogenesis of hepatic encephalopathy and cachexia. The unique pharmacologic properties of BCAA also are a factor for use as supplementation in this population. In the present article, BCAA is shown to provide nitrogen to alpha-ketoglutarate (α-KG) for synthesis of glutamate, which is a substrate for ammonia detoxification to glutamine (GLN) in the brain and muscles...
September 2017: Nutrition
https://www.readbyqxmd.com/read/28744296/metabolomic-analysis-of-alfalfa-medicago-sativa-l-root-symbiotic-rhizobia-responses-under-alkali-stress
#5
Tingting Song, Huihui Xu, Na Sun, Liu Jiang, Pu Tian, Yueyuan Yong, Weiwei Yang, Hua Cai, Guowen Cui
Alkaline salts (e.g., NaHCO3 and Na2CO3) causes more severe morphological and physiological damage to plants than neutral salts (e.g., NaCl and Na2SO4) due to differences in pH. The mechanism by which plants respond to alkali stress is not fully understood, especially in plants having symbotic relationships such as alfalfa (Medicago sativa L.). Therefore, a study was designed to evaluate the metabolic response of the root-nodule symbiosis in alfalfa under alkali stress using comparative metabolomics. Rhizobium-nodulized (RI group) and non-nodulized (NI group) alfalfa roots were treated with 200 mmol/L NaHCO3 and, roots samples were analyzed for malondialdehydyde (MDA), proline, glutathione (GSH), superoxide dismutase (SOD), and peroxidase (POD) content...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28659379/glutamine-fuels-proliferation-but-not-migration-of-endothelial-cells
#6
Boa Kim, Jia Li, Cholsoon Jang, Zoltan Arany
Endothelial metabolism is a key regulator of angiogenesis. Glutamine metabolism in endothelial cells (ECs) has been poorly studied. We used genetic modifications and (13)C tracing approaches to define glutamine metabolism in these cells. Glutamine supplies the majority of carbons in the tricyclic acid (TCA) cycle of ECs and contributes to lipid biosynthesis via reductive carboxylation. EC-specific deletion in mice of glutaminase, the initial enzyme in glutamine catabolism, markedly blunts angiogenesis. In cell culture, glutamine deprivation or inhibition of glutaminase prevents EC proliferation, but does not prevent cell migration, which relies instead on aerobic glycolysis...
August 15, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28653623/replication-study-the-common-feature-of-leukemia-associated-idh1-and-idh2-mutations-is-a-neomorphic-enzyme-activity-converting-alpha-ketoglutarate-to-2-hydroxyglutarate
#7
Megan Reed Showalter, Jason Hatakeyama, Tomas Cajka, Kacey VanderVorst, Kermit L Carraway, Oliver Fiehn
In 2016, as part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Fiehn et al., 2016), that described how we intended to replicate selected experiments from the paper "The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alpha-ketoglutarate to 2-hydroxyglutarate" (Ward et al., 2010). Here, we report the results of those experiments. We found that cells expressing R172K mutant IDH2 did not display isocitrate-dependent NADPH production above vector control levels, in contrast to the increased production observed with wild-type IDH2...
June 27, 2017: ELife
https://www.readbyqxmd.com/read/28629719/alpha-ketoglutarate-nanoparticles-a-potentially-effective-treatment-for-cyanide-poisoning
#8
Shaheen Sultana, Sushma Talegaonkar, Dhruv Kumar Nishad, Gaurav Mittal, F J Ahmad, Aseem Bhatnagar
The purpose of this research work was to prepare nanosized formulation of alpha ketoglutarate as dry powder inhaler for cyanide poisoning. Nanosizing can be approached by solid phase and liquid phase method. The different conditions encountered in both these approaches can greatly affect the particle characteristics. In this study milling and precipitation technique were compared to study their effect on α-KG particles characteristics. Differences in choice of stabilizers were observed between the two processing techniques...
June 16, 2017: European Journal of Pharmaceutics and Biopharmaceutics
https://www.readbyqxmd.com/read/28623373/metabolic-and-evolutionary-patterns-in-the-extremely-acidophilic-archaeon-ferroplasma-acidiphilum-y-t
#9
Olga V Golyshina, Hai Tran, Oleg N Reva, Sofia Lemak, Alexander F Yakunin, Alexander Goesmann, Taras Y Nechitaylo, Violetta LaCono, Francesco Smedile, Alexei Slesarev, David Rojo, Coral Barbas, Manuel Ferrer, Michail M Yakimov, Peter N Golyshin
Ferroplasmaceae represent ubiquitous iron-oxidising extreme acidophiles with a number of unique physiological traits. In a genome-based study of Ferroplasma acidiphilum Y(T), the only species of the genus Ferroplasma with a validly published name, we assessed its central metabolism and genome stability during a long-term cultivation experiment. Consistently with physiology, the genome analysis points to F. acidiphilum Y(T) having an obligate peptidolytic oligotrophic lifestyle alongside with anaplerotic carbon assimilation...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28579060/human-dihydrolipoamide-dehydrogenase-e3-deficiency-novel-insights-into-the-structural-basis-and-molecular-pathomechanism
#10
REVIEW
Attila Ambrus, Vera Adam-Vizi
This review summarizes our present view on the molecular pathogenesis of human (h) E3-deficiency caused by a variety of genetic alterations with a special emphasis on the moonlighting biochemical phenomena related to the affected (dihydro)lipoamide dehydrogenase (LADH, E3, gene: dld), in particular the generation of reactive oxygen species (ROS). E3-deficiency is a rare autosomal recessive genetic disorder frequently presenting with a neonatal onset and premature death; the highest carrier rate of a single pathogenic dld mutation (1:94-1:110) was found among Ashkenazi Jews...
June 2, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28508835/beneficial-influence-of-ellagic-acid-on-biochemical-indexes-associated-with-experimentally-induced-colon-carcinogenesis
#11
Umesalma Syed, Sudhandiran Ganapasam
OBJECTIVE: To elucidate the key biochemical indexes associated with 1, 2-dimethylhydrazine (DMH)-induced colon carcinogenesis and the modulatory efficacy of a dietary polyphenol, ellagic acid (EA). MATERIALS AND METHODS: Wistar rats were chosen to study objective, and were divided into 4 groups; Group 1-control rats; Group 2-rats received EA (60 mg/kg body weight/day, orally); rats in Group 3-induced with DMH (20 mg/kg body weight) subcutaneously for 15 weeks; DMH-induced Group 4 rats were initiated with EA treatment...
January 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28469248/pii-protein-derived-fret-sensors-for-quantification-and-live-cell-imaging-of-2-oxoglutarate
#12
Jan Lüddecke, Liliana Francois, Philipp Spät, Björn Watzer, Tomasz Chilczuk, Gernot Poschet, Rüdiger Hell, Bernhard Radlwimmer, Karl Forchhammer
The citric acid cycle intermediate 2-oxoglutarate (2-OG, a.k.a. alpha-ketoglutarate) links the carbon and nitrogen metabolic pathways and can provide information on the metabolic status of cells. In recent years, it has become exceedingly clear that 2-OG also acts as a master regulator of diverse biologic processes in all domains of life. Consequently, there is a great demand for time-resolved data on 2-OG fluctuations that can't be adequately addressed using established methods like mass spectrometry-based metabolomics analysis...
May 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28465471/alpha-ketoglutarate-akg-lowers-body-weight-and-affects-intestinal-innate-immunity-through-influencing-intestinal-microbiota
#13
Shuai Chen, Peng Bin, Wenkai Ren, Wei Gao, Gang Liu, Jie Yin, Jielin Duan, Yinghui Li, Kang Yao, Ruilin Huang, Bie Tan, Yulong Yin
Alpha-ketoglutarate (AKG), a precursor of glutamate and a critical intermediate in the tricarboxylic acid cycle, shows beneficial effects on intestinal function. However, the influence of AKG on the intestinal innate immune system and intestinal microbiota is unknown. This study explores the effect of oral AKG administration in drinking water (10 g/L) on intestinal innate immunity and intestinal microbiota in a mouse model. Mouse water intake, feed intake and body weight were recorded throughout the entire experiment...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28463998/plasma-metabolomics-reveals-a-diagnostic-metabolic-fingerprint-for-mitochondrial-aconitase-aco2-deficiency
#14
Lucia Abela, Ronen Spiegel, Lisa M Crowther, Andrea Klein, Katharina Steindl, Sorina Mihaela Papuc, Pascal Joset, Yoav Zehavi, Anita Rauch, Barbara Plecko, Thomas Luke Simmons
Mitochondrial respiratory chain dysfunction has been identified in a number of neurodegenerative disorders. Infantile cerebellar-retinal degeneration associated with mutations in the mitochondrial aconitase 2 gene (ACO2) has been recently described as a neurodegenerative disease of autosomal recessive inheritance. To date there is no biomarker for ACO2 deficiency and diagnosis relies on genetic analysis. Here we report global metabolic profiling in eight patients with ACO2 deficiency. Using an LC-MS-based metabolomics platform we have identified several metabolites with affected plasma concentrations including the tricarboxylic acid cycle metabolites cis-aconitate, isocitrate and alpha-ketoglutarate, as well as phosphoenolpyruvate and hydroxybutyrate...
2017: PloS One
https://www.readbyqxmd.com/read/28430654/alpha-ketoglutarate-suppresses-the-nf-%C3%AE%C2%BAb-mediated-inflammatory-pathway-and-enhances-the-pxr-regulated-detoxification-pathway
#15
Liuqin He, Huan Li, Niu Huang, Xihong Zhou, Junquan Tian, Tiejun Li, Jing Wu, Yanan Tian, Yulong Yin, Kang Yao
Alpha-ketoglutarate (AKG) is a critical nutritional factor in the maintenance of intestinal homeostasis. However, the relative mechanism of AKG has not been well understood. It was recently shown that the interaction between nuclear factor kappa B (NF-κB)-mediated inflammatory pathway and pregnane X receptor (PXR)-regulated detoxification pathway is a check and balance mechanism for keeping the homeostatic state of the intestine, preventing the onset of intestinal inflammation which may lead to cancer. In the current study we used lipopolysaccharide (LPS)-challenged piglet and intestinal porcine epithelial cells-J2 models to investigate the effects of dietary AKG supplementation on the intestinal immune system and PXR regulated target expression...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28398002/alpha-ketoglutarate-curbs-differentiation-and-induces-cell-death-in-mesenchymal-stromal-precursors-with-mitochondrial-dysfunction
#16
Karmveer Singh, Linda Krug, Abhijit Basu, Patrick Meyer, Nicolai Treiber, Seppe Vander Beken, Meinhard Wlaschek, Stefan Kochanek, Wilhelm Bloch, Hartmut Geiger, Pallab Maity, Karin Scharffetter-Kochanek
Increased concentrations of reactive oxygen species (ROS) originating from dysfunctional mitochondria contribute to diverse aging-related degenerative disorders. But so far little is known about the impact of distinct ROS on metabolism and fate of stromal precursor cells. Here, we demonstrate that an increase in superoxide anion radicals due to superoxide dismutase 2 (Sod2) deficiency in stromal precursor cells suppress osteogenic and adipogenic differentiation through fundamental changes in the global metabolite landscape...
April 11, 2017: Stem Cells
https://www.readbyqxmd.com/read/28387648/dysmorphic-features-frontal-cerebral-cavernoma-and-hyperglycemia-in-a-girl-with-a-de-novo-deletion-of-7-23-mb-in-region-7p13-p12-1
#17
Gilberto Pérez López, Beatriz Villafuerte Quispe, María José Cabrejas Núñez, Luis Castaño, Raquel Barrio
We describe the case of a 7 year old girl referred to our Diabetes Unit for hyperglycemia associated to facial dysmorphic features, intellectual disability and cerebral cavernomas, who was initially diagnosed with type 1 diabetes mellitus (positive anti-IA2 antibody and HLA DR3/DR4/DQ2). In follow up, due to the evolution of the diabetes (very good metabolic control with low insulin dose and negative IA-2 antibodies - samples analyzed in two different laboratories-), first clinical suspicion was GCK-related Maturity-Onset Diabetes of the Young (MODY 2) by persistent mild hyperglycemia in the fasting state, which was substantiated in Multiplex Ligation-dependent Probe Amplification (MLPA)...
April 7, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/28378142/functional-characterization-and-transcriptional-analysis-of-icd2-gene-encoding-an-isocitrate-dehydrogenase-of-xanthomonas-campestris-pv-campestris
#18
Ying-Chuan Chiang, Chao-Tsai Liao, Shin-Chiao Du, Yi-Min Hsiao
Isocitrate dehydrogenase (IDH) catalyzes the oxidative decarboxylation of isocitrate to alpha-ketoglutarate. In the genome of Xanthomonas campestris pv. campestris, the phytopathogen that causes black rot in cruciferous plants, two putative IDH genes, icd1 and icd2, have been annotated. Their physiological roles in X. campestris pv. campestris are unclear. In this study, the icd2 gene from X. campestris pv. campestris was characterized in detail. We demonstrated genetically that icd2 gene encodes a functional IDH, and is involved in virulence as well as bacterial attachment...
April 4, 2017: Archives of Microbiology
https://www.readbyqxmd.com/read/28275132/impact-of-polyunsaturated-and-saturated-fat-overfeeding-on-the-dna-methylation-pattern-in-human-adipose-tissue-a-randomized-controlled-trial
#19
RANDOMIZED CONTROLLED TRIAL
Alexander Perfilyev, Ingrid Dahlman, Linn Gillberg, Fredrik Rosqvist, David Iggman, Petr Volkov, Emma Nilsson, Ulf Risérus, Charlotte Ling
Background: Dietary fat composition can affect ectopic lipid accumulation and, thereby, insulin resistance. Diets that are high in saturated fatty acids (SFAs) or polyunsaturated fatty acids (PUFAs) have different metabolic responses.Objective: We investigated whether the epigenome of human adipose tissue is affected differently by dietary fat composition and general overfeeding in a randomized trial.Design: We studied the effects of 7 wk of excessive SFA (n = 17) or PUFA (n = 14) intake (+750 kcal/d) on the DNA methylation of ∼450,000 sites in human subcutaneous adipose tissue...
April 2017: American Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28273642/idh-mutations-associated-impact-on-related-cancer-epidemiology-and-subsequent-effect-toward-hif-1%C3%AE
#20
REVIEW
Herve Semukunzi, Debmalya Roy, Hongyang Li, Ghulam Jilany Khan, Xiaodan Lyu, Shengtao Yuan, Sensen Lin
Particular mutations in the isocitrate dehydrogenase gene (IDH) were discovered in several gliomas citing astrocytoma, oligodendroglioma, and glioblastoma multiform, but also in leukemia; these mutations were discovered in nearly all cases of secondary glioblastomas, they evolve from lower-grade gliomas, but are limited in primary high-grade glioblastoma multiform. These mutations distinctively produce (D)-2-hydroxyglutarate (D-2-HG) from alpha-ketoglutarate (α-KG). (D)-2-hydroxyglutarate is accumulated to very high concentrations which inhibit the function of enzymes that are dependent on alpha-ketoglutarate...
May 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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