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intracellular metabolism

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https://www.readbyqxmd.com/read/28231490/lipid-droplet-growth-regulation-of-a-dynamic-organelle
#1
REVIEW
David Barneda, Mark Christian
Intracellular lipid droplets (LDs) are remarkably dynamic and complex organelles that enact regulated storage and release of lipids to fulfil their fundamental roles in energy metabolism, membrane synthesis and provision of lipid-derived signaling molecules. Although small LDs are observed in all types of eukaryotic cells, it is adipocytes that present the widest range of sizes up to the massive unilocular droplet of a white adipocyte. Our knowledge of the proteins and associated processes that control LD dynamics is improving...
February 20, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28231413/metabolic-chemical-reporters-of-glycans-exhibit-cell-type-selective-metabolism-and-glycoprotein-labeling
#2
Anna R Batt, Balyn W Zaro, Marisol X Navarro, Matthew Robert Pratt
Since the pioneering work by Reutter and co-workers that demonstrated structural flexibility in the carbohydrate biosynthesis and glycosylation pathways, many different labs have used unnatural monosaccharide analogs to perform glycan engineering on the surface of living cells. A subset of these unnatural monosaccharides contain bioorthogonal groups that enable the selective installation of visualization or enrichment tags. These metabolic chemical reporters (MCRs) have proven to be powerful for the unbiased identification of glycoproteins; however they do have certain limitations...
February 23, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28231276/alterations-in-cellular-pharmacokinetics-and-pharmacodynamics-of-elvitegravir-in-response-to-ethanol-exposure-in-hiv-1-infected-monocytic-u1-cells
#3
Narasimha M Midde, Namita Sinha, Pradeep B Lukka, Bernd Meibohm, Santosh Kumar
Ethanol consumption is negatively associated with antiretroviral therapy (ART) adherence and general health in HIV positive individuals. Previously, we demonstrated ethanol-mediated alterations to metabolism of elvitegravir (EVG) in human liver microsomes. In the current study, we investigated ethanol influence on the pharmacokinetic and pharmacodynamic interactions of EVG in HIV infected monocytic (U1) cells. U1 cells were treated with 5 μM EVG, 2 μM Cobicistat (COBI), a booster drug, and 20 mM ethanol for up to 24 hours...
2017: PloS One
https://www.readbyqxmd.com/read/28230866/oridonin-induces-autophagy-via-inhibition-of-glucose-metabolism-in-p53-mutated-colorectal-cancer-cells
#4
Zhuo Yao, Fuhua Xie, Min Li, Zirui Liang, Wenli Xu, Jianhua Yang, Chang Liu, Hongwangwang Li, Hui Zhou, Liang-Hu Qu
The Warburg effect is an important characteristic of tumor cells, making it an attractive therapeutic target. Current anticancer drug development strategies predominantly focus on inhibitors of the specific molecular effectors involved in tumor cell proliferation. These drugs or natural compounds, many of which target the Warburg effect and the underlying mechanisms, still need to be characterized. To elucidate the anticancer effects of a natural diterpenoid, oridonin, we first demonstrated the anticancer activity of oridonin both in vitro and in vivo in colorectal cancer (CRC) cells...
February 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28230109/pentose-sugars-inhibit-metabolism-and-increase-expression-of-an-agrd-type-cyclic-pentapeptide-in-clostridium-thermocellum
#5
Tobin J Verbeke, Richard J Giannone, Dawn M Klingeman, Nancy L Engle, Thomas Rydzak, Adam M Guss, Timothy J Tschaplinski, Steven D Brown, Robert L Hettich, James G Elkins
Clostridium thermocellum could potentially be used as a microbial biocatalyst to produce renewable fuels directly from lignocellulosic biomass due to its ability to rapidly solubilize plant cell walls. While the organism readily ferments sugars derived from cellulose, pentose sugars from xylan are not metabolized. Here, we show that non-fermentable pentoses inhibit growth and end-product formation during fermentation of cellulose-derived sugars. Metabolomic experiments confirmed that xylose is transported intracellularly and reduced to the dead-end metabolite xylitol...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28229250/role-of-mirnas-in-human-disease-and-inborn-errors-of-metabolism
#6
Ana Rivera-Barahona, Belén Pérez, Eva Richard, Lourdes R Desviat
MicroRNAs (miRNAs) are short, noncoding RNAs that regulate gene expression posttranscriptionally by base pairing with target messenger RNAs (mRNAs). They are estimated to target ∼60% of all human protein-coding genes and are involved in regulating key physiological processes and intracellular signaling pathways. They also exhibit tissue specificity, and their dysregulation is linked to the progression of pathology. Identifying disease associated miRNAs and their respective targets provides novel molecular insight into disease, enabling the design of new therapeutic strategies...
February 22, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28229048/anaplasma-phagocytophilum-infection-subverts-carbohydrate-metabolic-pathways-in-the-tick-vector-ixodes-scapularis
#7
Alejandro Cabezas-Cruz, Pilar Alberdi, James J Valdés, Margarita Villar, José de la Fuente
The obligate intracellular pathogen, Anaplasma phagocytophilum, is the causative agent of human, equine, and canine granulocytic anaplasmosis and tick-borne fever (TBF) in ruminants. A. phagocytophilum has become an emerging tick-borne pathogen in the United States, Europe, Africa, and Asia, with increasing numbers of infected people and animals every year. It has been recognized that intracellular pathogens manipulate host cell metabolic pathways to increase infection and transmission in both vertebrate and invertebrate hosts...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28228748/chromogranin-a-regulation-of-obesity-and-peripheral-insulin-sensitivity
#8
REVIEW
Gautam K Bandyopadhyay, Sushil K Mahata
Chromogranin A (CgA) is a prohormone and granulogenic factor in endocrine and neuroendocrine tissues, as well as in neurons, and has a regulated secretory pathway. The intracellular functions of CgA include the initiation and regulation of dense-core granule biogenesis and sequestration of hormones in neuroendocrine cells. This protein is co-stored and co-released with secreted hormones. The extracellular functions of CgA include the generation of bioactive peptides, such as pancreastatin (PST), vasostatin, WE14, catestatin (CST), and serpinin...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28228470/a-conditional-mutant-of-the-fatty-acid-synthase-unveils-unexpected-cross-talks-in-mycobacterial-lipid-metabolism
#9
Matías Cabruja, Sonia Mondino, Yi Ting Tsai, Julia Lara, Hugo Gramajo, Gabriela Gago
Unlike most bacteria, mycobacteria rely on the multi-domain enzyme eukaryote-like fatty acid synthase I (FAS I) to make fatty acids de novo. These metabolites are precursors of the biosynthesis of most of the lipids present both in the complex mycobacteria cell wall and in the storage lipids inside the cell. In order to study the role of the type I FAS system in Mycobacterium lipid metabolism in vivo, we constructed a conditional mutant in the fas-acpS operon of Mycobacterium smegmatis and analysed in detail the impact of reduced de novo fatty acid biosynthesis on the global architecture of the cell envelope...
February 2017: Open Biology
https://www.readbyqxmd.com/read/28226770/a-multiscale-model-based-analysis-of-the-multi-tissue-interplay-underlying-blood-glucose-regulation-in-type-i-diabetes
#10
Federico Wadehn, Stephan Schaller, Thomas Eissing, Markus Krauss, Lars Kupfer, Federico Wadehn, Stephan Schaller, Thomas Eissing, Markus Krauss, Lars Kupfer, Federico Wadehn, Markus Krauss, Lars Kupfer, Stephan Schaller, Thomas Eissing
A multiscale model for blood glucose regulation in diabetes type I patients is constructed by integrating detailed metabolic network models for fat, liver and muscle cells into a whole body physiologically-based pharmacokinetic/pharmacodynamic (pBPK/PD) model. The blood glucose regulation PBPK/PD model simulates the distribution and metabolization of glucose, insulin and glucagon on an organ and whole body level. The genome-scale metabolic networks in contrast describe intracellular reactions. The developed multiscale model is fitted to insulin, glucagon and glucose measurements of a 48h clinical trial featuring 6 subjects and is subsequently used to simulate (in silico) the influence of geneknockouts and drug-induced enzyme inhibitions on whole body blood glucose levels...
August 2016: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/28225057/intracellular-drug-bioavailability-a-new-predictor-of-system-dependent-drug-disposition
#11
André Mateus, Andrea Treyer, Christine Wegler, Maria Karlgren, Pär Matsson, Per Artursson
Intracellular drug exposure is influenced by cell- and tissue-dependent expression of drug-transporting proteins and metabolizing enzymes. Here, we introduce the concept of intracellular bioavailability (Fic) as the fraction of extracellular drug available to bind intracellular targets, and we assess how Fic is affected by cellular drug disposition processes. We first investigated the impact of two essential drug transporters separately, one influx transporter (OATP1B1; SLCO1B1) and one efflux transporter (P-gp; ABCB1), in cells overexpressing these proteins...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28224106/impact-of-high-dose-vitamin-c-on-platelet-function
#12
Bassem M Mohammed, Kimberly W Sanford, Bernard J Fisher, Erika J Martin, Daniel Contaifer, Urszula Osinska Warncke, Dayanjan S Wijesinghe, Charles E Chalfant, Donald F Brophy, Alpha A Fowler Iii, Ramesh Natarajan
AIM: To examine the effect of high doses of vitamin C (VitC) on ex vivo human platelets (PLTs). METHODS: Platelet concentrates collected for therapeutic or prophylactic transfusions were exposed to: (1) normal saline (control); (2) 0.3 mmol/L VitC (Lo VitC); or (3) 3 mmol/L VitC (Hi VitC, final concentrations) and stored appropriately. The VitC additive was preservative-free buffered ascorbic acid in water, pH 5.5 to 7.0, adjusted with sodium bicarbonate and sodium hydroxide...
February 4, 2017: World Journal of Critical Care Medicine
https://www.readbyqxmd.com/read/28223936/two-pore-channels-catalyzers-of-endolysosomal-transport-and-function
#13
REVIEW
Christian Grimm, Cheng-Chang Chen, Christian Wahl-Schott, Martin Biel
Two-pore channels (TPCs) have recently emerged as a novel class of non-selective cation channels in the endolysosomal system. There are two members in the human genome, TPC1 and TPC2. Studies with TPC knockout and knockdown models have revealed that these channels participate in the regulation of multiple endolysosomal trafficking pathways which when dysregulated can lead to or influence the development of a range of different diseases such as lysosomal storage, metabolic, or infectious diseases. TPCs have been demonstrated to be activated by different endogenous stimuli, PI(3,5)P2 and NAADP, and ATP has been found to block TPC activation via mTOR...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28223907/comparative-bioavailability-and-utilization-of-particular-forms-of-b12-supplements-with-potential-to-mitigate-b12-related-genetic-polymorphisms
#14
REVIEW
Cristiana Paul, David M Brady
CONTEXT: Three natural forms of vitamin B12 are commercially available: methylcobalamin (MeCbl), adenosylcobalamin (AdCbl), and hydroxycobalamin (OHCbl), all of which have been shown in clinical studies to improve vitamin B12 status. They are bioidentical to the B12 forms occurring in human physiology and animal foods. In contrast, cyanocobalamin (CNCbl), a synthetic B12 compound used for food fortification and in some supplements, occurs only in trace amounts in human tissues as a result of cyanide intake from smoking or other sources...
February 2017: Integrative Medicine
https://www.readbyqxmd.com/read/28223334/corneal-surface-glycosylation-is-modulated-by-il-1r-and-pseudomonas-aeruginosa-challenge-but-is-insufficient-for-inhibiting-bacterial-binding
#15
Amber L Jolly, Paresh Agarwal, Matteo M E Metruccio, David R Spiciarich, David J Evans, Carolyn R Bertozzi, Suzanne M J Fleiszig
Cell surface glycosylation is thought to be involved in barrier function against microbes at mucosal surfaces. Previously we showed that the epithelium of healthy mouse corneas becomes vulnerable to P. aeruginosa adhesion if it lacks the innate defense protein MyD88 (myeloid differentiation primary response gene 88), or after superficial injury by blotting with tissue paper. Here we explored their effect on corneal surface glycosylation using a metabolic label, tetra-acetylated N-azidoacetylgalactosamine (Ac4GalNAz)...
February 21, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28223285/butyrate-regulates-liver-mitochondrial-function-efficiency-and-dynamic-in-insulin-resistant-obese-mice
#16
Maria Pina Mollica, Giuseppina Mattace Raso, Gina Cavaliere, Giovanna Trinchese, Chiara De Filippo, Serena Aceto, Marina Prisco, Claudio Pirozzi, Francesca Di Guida, Adriano Lama, Marianna Crispino, Diana Tronino, Paola Di Vaio, Roberto Berni Canani, Antonio Calignano, Rosaria Meli
Fatty liver, oxidative stress, and mitochondrial dysfunction are key pathophysiological features of insulin resistance and obesity. Butyrate, produced by fermentation in the large intestine by gut microbiota, and its synthetic derivative, the N-(1-carbamoyl-2-phenyl-ethyl) butyramide, FBA, have been demonstrated to be protective against insulin resistance and fatty liver.Here, hepatic mitochondria were identified as the main target of the beneficial effect of both butyrate-based compounds in reverting insulin resistance and fat accumulation in diet induced obese mice...
February 21, 2017: Diabetes
https://www.readbyqxmd.com/read/28223003/treatment-of-metformin-intoxication-complicated-by-lactic-acidosis-and-acute-kidney-injury-the-role-of-prolonged-intermittent-hemodialysis
#17
Giuseppe Regolisti, Riccardo Antoniotti, Filippo Fani, Paolo Greco, Enrico Fiaccadori
Metformin intoxication with lactic acidosis, a potentially lethal condition, may develop in diabetic patients when the drug dose is inappropriate and/or its clearance is reduced. Diagnosis and therapy may be delayed due to nonspecific symptoms at presentation, with severe anion gap metabolic acidosis and elevated serum creatinine values being the most prominent laboratory findings. Confirmation requires measurement of serum metformin by high-performance liquid chromatography-tandem mass spectrometry, but this technique is available only at specialized institutions and cannot be relied on as a guide to immediate treatment...
February 17, 2017: American Journal of Kidney Diseases: the Official Journal of the National Kidney Foundation
https://www.readbyqxmd.com/read/28222432/extracellular-hmgb1-modulates-glutamate-metabolism-associated-with-kainic-acid-induced-epilepsy-like-hyperactivity-in-primary-rat-neural-cells
#18
Yuji Kaneko, Colleen Pappas, Teresita Malapira, Fernando Ĺ Vale, Naoki Tajiri, Cesar V Borlongan
BACKGROUND/AIMS: Neuroinflammatory processes have been implicated in the pathophysiology of seizure/epilepsy. High mobility group box 1 (HMGB1), a non-histone DNA binding protein, behaves like an inflammatory cytokine in response to epileptogenic insults. Kainic acid (KA) is an excitotoxic reagent commonly used to induce epilepsy in rodents. However, the molecular mechanism by which KA-induced HMGB1 affords the initiation of epilepsy, especially the role of extracellular HMGB1 in neurotransmitter expression, remains to be elucidated...
February 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28221344/chemoproteomic-profiling-and-discovery-of-protein-electrophiles-in-human-cells
#19
Megan L Matthews, Lin He, Benjamin D Horning, Erika J Olson, Bruno E Correia, John R Yates, Philip E Dawson, Benjamin F Cravatt
Activity-based protein profiling (ABPP) serves as a chemical proteomic platform to discover and characterize functional amino acids in proteins on the basis of their enhanced reactivity towards small-molecule probes. This approach, to date, has mainly targeted nucleophilic functional groups, such as the side chains of serine and cysteine, using electrophilic probes. Here we show that 'reverse-polarity' (RP)-ABPP using clickable, nucleophilic hydrazine probes can capture and identify protein-bound electrophiles in cells...
March 2017: Nature Chemistry
https://www.readbyqxmd.com/read/28220845/heterogeneous-nuclear-ribonucleoprotein-a1-regulates-rhythmic-synthesis-of-mouse-nfil3-protein-via-ires-mediated-translation
#20
Hyo-Jin Kim, Hwa-Rim Lee, Ji-Young Seo, Hye Guk Ryu, Kyung-Ha Lee, Do-Yeon Kim, Kyong-Tai Kim
Nuclear factor, interleukin 3, regulated (Nfil3, also known as E4 Promoter-Binding Protein 4 (E4BP4)) protein is a transcription factor that binds to DNA and generally represses target gene expression. In the circadian clock system, Nfil3 binds to a D-box element residing in the promoter of clock genes and contributes to their robust oscillation. Here, we show that the 5'-untranslated region (5'-UTR) of Nfil3 mRNA contains an internal ribosome entry site (IRES) and that IRES-mediated translation occurs in a phase-dependent manner...
February 21, 2017: Scientific Reports
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