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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
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
A Young Kim, Kyeong-Hoon Jeong, Jae Ho Lee, Yup Kang, Soo Hwan Lee, Eun Joo Baik
Deregulation of glutamate homeostasis is associated with degenerative neurological disorders. Glutamate dehydrogenase (GDH) is important for glutamate metabolism and plays a central role in expanding the pool of tricarboxylic acid (TCA) cycle intermediate alpha-ketoglutarate (α-KG), which improves overall bioenergetics. Under high energy demand, maintenance of ATP production results in functionally active mitochondria. Here, we tested whether the modulation of GDH activity can rescue ischemia/reperfusion-induced neuronal death in an in vivo mouse model of middle artery occlusion and an in vitro oxygen/glucose depletion model...
November 12, 2016: Neuroscience
Hongwei Guo, Shaojie Su, Catherine Madzak, Jingwen Zhou, Hongwen Chen, Guo Chen
α-Ketoglutarate (α-KG), one of short-chain carboxylates of high commercial relevance, has been widely used in food, medicine, chemical, and cosmetic fields. Compared to other carboxylates, α-KG occupies key positions in the tricarboxylate cycle (TCA cycle) and amino acid metabolic pathway, the over-accumulation of α-KG is restricted both by tighter carbon and nitrogen regulation process. Biotechnology production of α-KG on large industrial level has been impeded by many obstacles. This review aims at highlighting and stating recent efforts toward improving the yield and titer of α-KG in the strains of Yarrowia lipolytica to reach industrial relevance...
October 29, 2016: Applied Microbiology and Biotechnology
Maria M Bayliak, Halyna V Shmihel, Maria P Lylyk, Kenneth B Storey, Volodymyr I Lushchak
Ethanol at low concentrations (<4%) can serve as a food source for fruit fly Drosophila melanogaster, whereas at higher concentrations it may be toxic. In this work, protective effects of dietary alpha-ketoglutarate (AKG) against ethanol toxicity were studied. Food supplementation with 10-mM AKG alleviated toxic effects of 8% ethanol added to food, and improved fly development. Two-day-old adult flies, reared on diet containing both AKG and ethanol, possessed higher alcohol dehydrogenase (ADH) activity as compared with those reared on control diet or diet with ethanol only...
September 2016: Alcohol
Eric L Allen, Danielle B Ulanet, David Pirman, Christopher E Mahoney, John Coco, Yaguang Si, Ying Chen, Lingling Huang, Jinmin Ren, Sung Choe, Michelle F Clasquin, Erin Artin, Zi Peng Fan, Giovanni Cianchetta, Joshua Murtie, Marion Dorsch, Shengfang Jin, Gromoslaw A Smolen
Although aberrant metabolism in tumors has been well described, the identification of cancer subsets with particular metabolic vulnerabilities has remained challenging. Here, we conducted an siRNA screen focusing on enzymes involved in the tricarboxylic acid (TCA) cycle and uncovered a striking range of cancer cell dependencies on OGDH, the E1 subunit of the alpha-ketoglutarate dehydrogenase complex. Using an integrative metabolomics approach, we identified differential aspartate utilization, via the malate-aspartate shuttle, as a predictor of whether OGDH is required for proliferation in 3D culture assays and for the growth of xenograft tumors...
October 11, 2016: Cell Reports
Attila Ambrus, Junjie Wang, Reka Mizsei, Zsofia Zambo, Beata Torocsik, Frank Jordan, Vera Adam-Vizi
Pathogenic amino acid substitutions of the common E3 component (hE3) of the human alpha-ketoglutarate dehydrogenase and the pyruvate dehydrogenase complexes lead to severe metabolic diseases (E3 deficiency), which usually manifest themselves in cardiological and/or neurological symptoms and often cause premature death. To date, 14 disease-causing amino acid substitutions of the hE3 component have been reported in the clinical literature. None of the pathogenic protein variants has lent itself to high-resolution structure elucidation by X-ray or NMR...
November 2016: Biochimica et Biophysica Acta
Maria M Bayliak, Maria P Lylyk, Halyna V Shmihel, Oksana M Sorochynska, Oksana V Manyukh, Stefan G Pierzynowski, Volodymyr I Lushchak
Alpha-ketoglutarate (AKG) is an important intermediate in Krebs cycle which bridges the metabolism of amino acids and carbohydrates. Its effects as a dietary supplement on cold tolerance were studied in Drosophila melanogaster Canton S. Two-day-old adult flies fed at larval and adult stages with AKG at moderate concentrations (5-10mM) recovered faster from chill coma (0°C for 15min or 3h) than control ones. The beneficial effect of AKG on chill coma recovery was not found at its higher concentrations, which suggests hormetic like action of this keto acid...
August 2016: Journal of Thermal Biology
Elda M Rueda, Jerry E Johnson, Anand Giddabasappa, Anand Swaroop, Matthew J Brooks, Irena Sigel, Shawnta Y Chaney, Donald A Fox
PURPOSE: The homeostatic regulation of cellular ATP is achieved by the coordinated activity of ATP utilization, synthesis, and buffering. Glucose is the major substrate for ATP synthesis through glycolysis and oxidative phosphorylation (OXPHOS), whereas intermediary metabolism through the tricarboxylic acid (TCA) cycle utilizes non-glucose-derived monocarboxylates, amino acids, and alpha ketoacids to support mitochondrial ATP and GTP synthesis. Cellular ATP is buffered by specialized equilibrium-driven high-energy phosphate (~P) transferring kinases...
2016: Molecular Vision
Sanne A M van Lith, Anna C Navis, Krissie Lenting, Kiek Verrijp, Jan T G Schepens, Wiljan J A J Hendriks, Nil A Schubert, Hanka Venselaar, Ron A Wevers, Arno van Rooij, Pieter Wesseling, Remco J Molenaar, Cornelis J F van Noorden, Stefan Pusch, Bastiaan Tops, William P J Leenders
The majority of low-grade and secondary high-grade gliomas carry heterozygous hotspot mutations in cytosolic isocitrate dehydrogenase 1 (IDH1) or the mitochondrial variant IDH2. These mutations mostly involve Arg132 in IDH1, and Arg172 or Arg140 in IDH2. Whereas IDHs convert isocitrate to alpha-ketoglutarate (α-KG) with simultaneous reduction of NADP(+) to NADPH, these IDH mutants reduce α-KG to D-2-hydroxyglutarate (D-2-HG) while oxidizing NADPH. D-2-HG is a proposed oncometabolite, acting via competitive inhibition of α-KG-dependent enzymes that are involved in metabolism and epigenetic regulation...
2016: Scientific Reports
Tor-Christian Aase Johannessen, Joydeep Mukherjee, Pavithra Viswanath, Shigeo Ohba, Sabrina M Ronen, Rolf Bjerkvig, Russell O Pieper
: Missense mutations in the active site of isocitrate dehydrogenase 1 (IDH1) biologically and diagnostically distinguish low-grade gliomas and secondary glioblastomas from primary glioblastomas. IDH1 mutations lead to the formation of the oncometabolite 2-hydroxyglutarate (2-HG) from the reduction of α-ketoglutarate (α-KG), which in turn facilitates tumorigenesis by modifying DNA and histone methylation as well blocking differentiation processes. Although mutant IDH1 expression is thought to drive the gliomagenesis process, the extent to which it remains a viable therapeutic target remains unknown...
October 2016: Molecular Cancer Research: MCR
Guiwei Kao, Lili Qiu, Qi Peng, Jie Zhang, Jie Li, Fuping Song
OBJECTIVE: The study aimed to determine the appropriate stage for exploring the responseof Bacillus thuringiensis to the alkaline stress, to profile the metabolic pathways under this stress. METHODS: Using semi-quantitative RT-PCR and qRT-PCR, the proper stage was defined by monitoring the transcriptional changes of marker gene pspA, which was known as a responsive gene under the alkaline stress. The total RNA was then extracted to perform the microarray hybridizations for samples under stress and control, respectively...
March 4, 2016: Wei Sheng Wu Xue Bao, Acta Microbiologica Sinica
Alison M Mondul, Stephanie J Weinstein, Demetrius Albanes
PURPOSE: How micronutrients might influence risk of developing adenocarcinoma of the prostate has been the focus of a large body of research (especially regarding vitamins E, A, and D). Metabolomic profiling has the potential to discover molecular species relevant to prostate cancer etiology, early detection, and prevention, and may help elucidate the biologic mechanisms through which vitamins influence prostate cancer risk. METHODS: Prostate cancer risk data related to vitamins E, A, and D and metabolomic profiling from clinical, cohort, and nested case-control studies, along with randomized controlled trials, are examined and summarized, along with recent metabolomic data of the vitamin phenotypes...
June 23, 2016: World Journal of Urology
Barbara Zdzisińska, Aleksandra Żurek, Martyna Kandefer-Szerszeń
Alpha-ketoglutarate (AKG), an endogenous intermediary metabolite in the Krebs cycle, is a molecule involved in multiple metabolic and cellular pathways. It functions as an energy donor, a precursor in the amino acid biosynthesis, a signalling molecule, as well as a regulator of epigenetic processes and cellular signalling via protein binding. AKG is an obligatory co-substrate for 2-oxoglutarate-dependent dioxygenases, which catalyse hydroxylation reactions on various types of substrates. It regulates the activity of prolyl-4 hydroxylase, which controls the biosynthesis of collagen, a component of bone tissue...
June 20, 2016: Archivum Immunologiae et Therapiae Experimentalis
Fei Yang, Wen Xiao, Xiaohua Ma, Ruixue Huang, Ran Yu, Guiyin Li, Xiao Huang, Cuimei Chen, Ping Ding
OBJECTIVES: A novel magnetic targeting anti-tumour drug delivery system (Fe3 O4 /KCTS-CHE) was designed using magnetic Fe3 O4 /chitosan alpha-ketoglutaric acid (Fe3 O4 /KCTS) as carrier and chelerythrine (CHE) as an anti-tumour drug model. Moreover, the anti-tumour activities and mechanisms of Fe3 O4 /KCTS-CHE were investigated. METHODS: The preparation conditions of Fe3 O4 /KCTS-CHE microspheres were optimized by response surface methodology (RSM). The CHE drug release kinetics was evaluated by fitting the experimental data to standard release equations...
August 2016: Journal of Pharmacy and Pharmacology
Huachen Chen, Lai-Sheung Lee, Guanwu Li, Sai-Wah Tsao, Jen-Fu Chiu
Arsenic and benzo[α]pyrene (B[a]P) are common contaminants in developing countries. Many studies have investigated the consequences of arsenic and/or B[a]P-induced cellular transformation, including altered metabolism. In the present study, we show that, in addition to elevated glycolysis, B[a]P/arsenic-induced transformation also stimulates oxidative phosphorylation (OXPHOS). Proteomic data and immunoblot studies demonstrated that enzymatic activities, involved in both glycolysis and OXPHOS, are upregulated in the primary transformed rat lung epithelial cell (TLEC) culture, as well as in subcloned TLEC cell lines (TMCs), indicating that OXPHOS was active and still contributed to energy production...
June 3, 2016: Oncotarget
R P Radzki, M Bieńko, R Filip, S G Pierzynowski
OBJECTIVE: This study investigated the effect of alpha-ketoglutarate sodium salt (AKG) and ipriflavone (IP) treatment on the mineralization of the tibia in male rats during the development and after the establishment of osteopenia. DESIGN: One hundred and twenty eight male rats were randomly selected and submitted to either sham-operation (SHO) or orchidectomy (ORX), after which each group were then randomly divided between the two experiments. In Experiment-1, treatment with AKG or/and IP started after a 7-day recovery period, whereas in Experiment-2, the experimental protocol proceeded after a 60-day period of osteopenia establishment...
2016: Journal of Nutrition, Health & Aging
Xingcai Cai, Canjun Zhu, Yaqiong Xu, Yuanyuan Jing, Yexian Yuan, Lina Wang, Songbo Wang, Xiaotong Zhu, Ping Gao, Yongliang Zhang, Qingyan Jiang, Gang Shu
Skeletal muscle weight loss is accompanied by small fiber size and low protein content. Alpha-ketoglutarate (AKG) participates in protein and nitrogen metabolism. The effect of AKG on skeletal muscle hypertrophy has not yet been tested, and its underlying mechanism is yet to be determined. In this study, we demonstrated that AKG (2%) increased the gastrocnemius muscle weight and fiber diameter in mice. Our in vitro study also confirmed that AKG dose increased protein synthesis in C2C12 myotubes, which could be effectively blocked by the antagonists of Akt and mTOR...
2016: Scientific Reports
Qian Jiang, Liuqin He, Yongqing Hou, Jiashun Chen, Yehui Duan, Dun Deng, Guoyao Wu, Yulong Yin, Kang Yao
Alpha-ketoglutarate (AKG), a key intermediate in the Krebs cycle, has been reported to promote protein synthesis through activating mechanistic targeting of rapamycin (mTOR) in enterocytes. The study tested the hypothesis that AKG may enhance growth and milk protein synthesis in porcine mammary epithelial cells (PMECs). PMECs were cultured for 96 h in Dulbecco's modified Eagle's-F12 Ham medium (DMEM-F12) containing prolactin (2 µg/ml) and AKG (0 or 1.5 mM). At the end of 96-h culture, the abundance of apoptosis-related proteins (caspase-3, caspase-9), milk-specific proteins (α-lactalbumin and β-casein), mTOR signaling proteins (mTOR, p-mTOR, PERK, p-PERK, eIF2a, P70S6K and p-P70S6K), and endoplasmic reticulum stress (ERS)-associated proteins (BiP and CHOP) in PMEC were determined...
September 2016: Amino Acids
Dingfu Xiao, Liming Zeng, Kang Yao, Xiangfeng Kong, Guoyao Wu, Yulong Yin
L-Glutamine is a nutritionally semi-essential amino acid for proper growth in most cells and tissues, and plays an important role in the determination and guarding of the normal metabolic processes of the cells. With the help of transport systems, extracellular L-glutamine crosses the plasma membrane and is converted into alpha-ketoglutarate (AKG) through two pathways, namely, the glutaminase (GLS) I and II pathway. Reversely, AKG can be converted into glutamine by glutamate dehydrogenase (GDH) and glutamine synthetase (GS), or be converted into CO2 via the tricarboxylic acid (TCA) cycle and provide energy for the cells...
September 2016: Amino Acids
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