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Alpha-ketoglutarate

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https://www.readbyqxmd.com/read/28508835/beneficial-influence-of-ellagic-acid-on-biochemical-indexes-associated-with-experimentally-induced-colon-carcinogenesis
#1
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
#2
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
#3
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...
April 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28463998/plasma-metabolomics-reveals-a-diagnostic-metabolic-fingerprint-for-mitochondrial-aconitase-aco2-deficiency
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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...
March 8, 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
#10
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
https://www.readbyqxmd.com/read/28268250/antioxidant-effect-of-thiazolidine-molecules-in-cell-culture-media-improves-stability-and-performance
#11
Jennifer Kuschelewski, Alisa Schnellbaecher, Sascha Pering, Maria Wehsling, Aline Zimmer
The ability of cell culture media components to generate reactive species as well as their sensitivity to oxidative degradation, affects the overall stability of media and the behavior of cells cultured in vitro. This study investigates the influence of thiazolidine molecules, formed from the condensation between cysteine and alpha-ketoacids, on the stability of these complex mixtures and on the performance of cell culture processes aiming to produce therapeutically relevant monoclonal antibodies. Results presented in this study indicate that 2-methyl-1,3-thiazolidine-2,4-dicarboxylic acid and 2-(2-carboxyethyl)-1,3-thiazolidine-2,4-dicarboxylic acid, obtained by condensation of cysteine with pyruvate or alpha-ketoglutarate respectively, are able to stabilize cell culture media formulations, in particular redox sensitive molecules like folic acid, thiamine, L-methionine (met) and L-tryptophan (trp)...
March 7, 2017: Biotechnology Progress
https://www.readbyqxmd.com/read/28216953/therapeutic-potential-of-alpha-ketoglutarate-against-acetaminophen-induced-hepatotoxicity-in-rats
#12
Lalita Mehra, Yasha Hasija, Gaurav Mittal
OBJECTIVE: Alpha-ketoglutarate (α-KG) is a cellular intermediary metabolite of Krebs cycle, involved in energy metabolism, amino acid synthesis, and nitrogen transport. It is available over-the-counter and marketed as a nutritional supplement. There is a growing body of evidence to suggest that dietary α-KG has the potential to maintain cellular redox status and thus can protect various oxidative stress induced disease states. The aim of the present study was to investigate the hepatoprotective role of α-KG in acetaminophen (APAP) induced toxicity in rats...
October 2016: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/28154578/growth-on-alpha-ketoglutarate-increases-oxidative-stress-resistance-in-the-yeast-saccharomyces-cerevisiae
#13
Maria Bayliak, Nadia Burdyliuk, Volodymyr Lushchak
Alpha-ketoglutarate (AKG) is an important intermediate in cell metabolism, linking anabolic and catabolic processes. The effect of exogenous AKG on stress resistance in S. cerevisiae cells was studied. The growth on AKG increased resistance of yeast cells to stresses, but the effects depended on AKG concentration and type of stressor. Wild-type yeast cells grown on AKG were more resistant to hydrogen peroxide, menadione, and transition metal ions (Fe(2+) and Cu(2+)) but not to ethanol and heat stress as compared with control ones...
2017: International Journal of Microbiology
https://www.readbyqxmd.com/read/28096758/effects-of-acute-ingestion-of-a-pre-workout-dietary-supplement-with-and-without-p-synephrine-on-resting-energy-expenditure-cognitive-function-and-exercise-performance
#14
Y Peter Jung, Conrad P Earnest, Majid Koozehchian, Elfego Galvan, Ryan Dalton, Dillon Walker, Christopher Rasmussen, Peter S Murano, Mike Greenwood, Richard B Kreider
BACKGROUND: The purpose of this study was to examine the effects of acute ingestion of a pre-workout dietary supplement (PWS) with and without p-synephrine (S) on perceptions of readiness to perform, cognitive function, exercise performance, and markers of safety. METHODS: In a randomized, double-blind, and counterbalanced manner; 25 healthy and recreationally active male and female participants ingested a flavored maltodextrin placebo (PLA), a PWS containing beta-alanine (3 g), creatine nitrate as a salt (2 g), arginine alpha-ketoglutarate (2 g), N-Acetyl-L-Tyrosine (300 mg), caffeine (284 mg), Mucuna pruiriens extract standardized for 15% L-Dopa (15 mg), Vitamin C as Ascorbic Acid (500 mg), niacin (60 mg), folate as folic acid (50 mg), and Vitamin B12 as Methylcobalamin (70 mg) with 2 g of maltodextrin and flavoring; or, the PWS with Citrus aurantium (PWS + S) extract standardized for 30% p-synephrine (20 mg)...
2017: Journal of the International Society of Sports Nutrition
https://www.readbyqxmd.com/read/28096757/effects-of-ingesting-a-pre-workout-dietary-supplement-with-and-without-synephrine-for-8%C3%A2-weeks-on-training-adaptations-in-resistance-trained-males
#15
Y Peter Jung, Conrad P Earnest, Majid Koozehchian, Minye Cho, Nick Barringer, Dillon Walker, Christopher Rasmussen, Mike Greenwood, Peter S Murano, Richard B Kreider
BACKGROUND: The purpose of this study was to examine whether ingesting a pre-workout dietary supplement (PWS) with and without synephrine (S) during training affects training responses in resistance-trained males. METHODS: Resistance-trained males (N = 80) were randomly assigned to supplement their diet in a double-blind manner with either a flavored placebo (PLA); a PWS containing beta-alanine (3 g), creatine nitrate as a salt (2 g), arginine alpha-ketoglutarate (2 g), N-Acetyl-L-Tyrosine (300 mg), caffeine (284 mg), Mucuna pruiriens extract standardized for 15% L-Dopa (15 mg), Vitamin C as Ascorbic Acid (500 mg), niacin (60 mg), folate as folic acid (50 mg), and Vitamin B12 as Methylcobalamin (70 mg); or, the PWS supplement with Citrus aurantium extract containing 20 mg of synephrine (PWS + S) once per day for 8-weeks during training...
2017: Journal of the International Society of Sports Nutrition
https://www.readbyqxmd.com/read/28017777/the-cardioprotective-effect-of-sildenafil-is-mediated-by-the-activation-of-malate-dehydrogenase-and-an-increase-in-the-malate-aspartate-shuttle-in-cardiomyocytes
#16
Federica Gevi, Federica Campolo, Fabio Naro, Lello Zolla
Recent evidence has shown the cardioprotective effect of PDE5 inhibition in myocardial ischemia/reperfusion injury, heart failure and cardiac hypertrophy. To investigate the biochemical changes that occur during PDE5 inhibition in cardiac cells, this study assessed the metabolic profile of the HL1 cell line, a murine atrial cell line with adult cardiomyocyte properties. After one hour of treatment with sildenafil, glycolysis was moderately but selectively stimulated, unlike the pentose phosphate pathway and the Krebs cycle...
March 1, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27940338/the-effect-of-alpha-ketoglutaric-acid-on-tyrosinase-activity-and-conformation-kinetics-and-molecular-dynamics-simulation-study
#17
Lin Gou, Jinhyuk Lee, Jun-Mo Yang, Yong-Doo Park, Hai-Meng Zhou, Yi Zhan, Zhi-Rong Lü
Alpha-ketoglutaric acid (AKG) is naturally found in organisms and is a well-known intermediate in the production of ATP or GTP in the Krebs cycle. We elucidated the effects of AKG on tyrosinase activity and conformation via methods of inhibition kinetics integrated with molecular dynamics (MD) simulations. AKG was found to be a reversible inhibitor of tyrosinase (IC50=15±0.5mM) and induced parabolic slope mixed-type inhibition. Based on our newly established equation, the dissociation constant (Kislope) was determined to be 7...
December 7, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27933337/biodegradation-of-the-herbicide-2-4-dichlorophenoxyacetic-acid-by-a-new-isolated-strain-of-achromobacter-sp-lz35
#18
Zhen-Yuan Xia, Long Zhang, Yan Zhao, Xin Yan, Shun-Peng Li, Tao Gu, Jian-Dong Jiang
In this study, a bacterial strain of Achromobacter sp. LZ35, which was capable of utilizing 2,4-dichlorophenoxyacetic acid (2,4-D) and 2-methyl-4-chlorophenoxy acetic acid (MCPA) as the sole sources of carbon and energy for growth, was isolated from the soil in a disused pesticide factory in Suzhou, China. The optimal 2,4-D degradation by strain LZ35 occurred at 30 °C and pH 8.0 when the initial 2,4-D concentration was 200 mg L(-1). Strain LZ35 harbored the conserved 2,4-D/alpha-ketoglutarate dioxygenase (96%) and 2,4-dichlorophenol hydroxylase (99%), and catabolized 2,4-D via the intermediate 2,4-dichlorophenol...
February 2017: Current Microbiology
https://www.readbyqxmd.com/read/27898998/nutritional-supplementation-for-hip-fracture-aftercare-in-older-people
#19
REVIEW
Alison Avenell, Toby O Smith, James P Curtain, Jenson Cs Mak, Phyo K Myint
BACKGROUND: Older people with hip fractures are often malnourished at the time of fracture, and subsequently have poor food intake. This is an update of a Cochrane review first published in 2000, and previously updated in 2010. OBJECTIVES: To review the effects (benefits and harms) of nutritional interventions in older people recovering from hip fracture. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, CENTRAL, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Embase, CAB Abstracts, CINAHL, trial registers and reference lists...
November 30, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27856334/quantitative-metabolic-flux-analysis-reveals-an-unconventional-pathway-of-fatty-acid-synthesis-in-cancer-cells-deficient-for-the-mitochondrial-citrate-transport-protein
#20
Lei Jiang, Adam Boufersaoui, Chendong Yang, Bookyung Ko, Dinesh Rakheja, Gerardo Guevara, Zeping Hu, Ralph J DeBerardinis
The mitochondrial citrate transport protein (CTP), encoded by SLC25A1, accommodates bidirectional trafficking of citrate between the mitochondria and cytosol, supporting lipid biosynthesis and redox homeostasis. Genetic CTP deficiency causes a fatal neurodevelopmental syndrome associated with the accumulation of L- and D-2-hydroxyglutaric acid, and elevated CTP expression is associated with poor prognosis in several types of cancer, emphasizing the importance of this transporter in multiple human pathologies...
November 14, 2016: Metabolic Engineering
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