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s-adenosyl-methionine

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https://www.readbyqxmd.com/read/29212039/comprehensive-mapping-of-pluripotent-stem-cell-metabolism-using-dynamic-genome-scale-network-modeling
#1
Sriram Chandrasekaran, Jin Zhang, Zhen Sun, Li Zhang, Christian A Ross, Yu-Chung Huang, John M Asara, Hu Li, George Q Daley, James J Collins
Metabolism is an emerging stem cell hallmark tied to cell fate, pluripotency, and self-renewal, yet systems-level understanding of stem cell metabolism has been limited by the lack of genome-scale network models. Here, we develop a systems approach to integrate time-course metabolomics data with a computational model of metabolism to analyze the metabolic state of naive and primed murine pluripotent stem cells. Using this approach, we find that one-carbon metabolism involving phosphoglycerate dehydrogenase, folate synthesis, and nucleotide synthesis is a key pathway that differs between the two states, resulting in differential sensitivity to anti-folates...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29194039/validation-of-a-high-performance-liquid-chromatography-method-for-thiopurine-s-methyltransferase-activity-in-whole-blood-using-6-mercaptopurine-as-substrate
#2
Hannah Rieger, Patrik Schmidt, Elke Schaeffeler, Manabu Abe, Mira Schiffhauer, Matthias Schwab, Nicolas von Ahsen, Gabriela Zurek, Hartmut Kirchherr, Maria Shipkova, Eberhard Wieland
BACKGROUND: Variation in metabolism, toxicity and therapeutic efficacy of thiopurine drugs is largely influenced by genetic polymorphisms in the thiopurine S-methyltransferase (TPMT) gene. Determination of TPMT activity is routinely performed in patients to adjust drug therapy. METHODS: We further optimized a previously established high-performance liquid chromatography (HPLC) method by measuring TPMT activity in whole blood instead of isolated erythrocytes, which is based on conversion of 6-mercaptopurine to 6-methylmercaptopurine using S-adenosyl-methionine as methyl donor...
December 1, 2017: Clinical Chemistry and Laboratory Medicine: CCLM
https://www.readbyqxmd.com/read/29180119/cyclopropane-fatty-acid-synthesis-affects-cell-shape-and-acid-resistance-in-leishmania-mexicana
#3
Wei Xu, Sumit Mukherjee, Yu Ning, Fong-Fu Hsu, Kai Zhang
Cyclopropane fatty acid synthase (CFAS) catalyzes the transfer of a methylene group from S-adenosyl methionine to an unsaturated fatty acid, generating a cyclopropane fatty acid (CFA). The gene encoding CFAS is present in many bacteria and several Leishmania spp. including Leishmania mexicana, Leishmania infantum and Leishmania braziliensis. In this study, we characterized the CFAS-null and -overexpression mutants in L. mexicana, the causative agent for cutaneous leishmaniasis in Mexico and central America...
November 24, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/29176927/conceptualizing-eukaryotic-metabolic-sensing-and-signaling
#4
Sunil Laxman
For almost all cells, nutrient availability, from glucose to amino acids, dictates their growth or developmental programs. This nutrient availability is closely coupled to the overall intracellular metabolic state of the cell. Therefore, cells have evolved diverse, robust and versatile modules to sense intracellular metabolic states, activate signaling outputs and regulate outcomes to these states. Yet, signaling and metabolism have been viewed as important but separate. This short review attempts to position aspects of intracellular signaling from a metabolic perspective, highlighting how conserved, core principles of metabolic sensing and signaling can emerge from an understanding of metabolic regulation...
March 2017: Journal of the Indian Institute of Science
https://www.readbyqxmd.com/read/29157356/effect-of-exogenous-progesterone-on-embryo-size-and-ewe-uterine-gene-expression-in-an-ovine-dam-size-model-of-maternal-constraint
#5
Lisanne M Fermin, Sarah J Pain, Patrick C H Morel, Kristene R Gedye, Paul R Kenyon, Hugh T Blair
Progesterone (P4), acting via its receptor, regulates uterine function and histotroph production, which are crucial to embryo growth. This study aimed to examine exogenous P4 effects on embryo size and differential endometrial gene expression at Day 19 of gestation using a 'dam size' sheep model of maternal constraint. Purebred Suffolk (S, genotypically large) embryos were transferred into recipient groups of Cheviot (C, genotypically small) or Suffolk ewes that had, or had not, been pre-treated with P4 from Days 0 to 6 of pregnancy...
November 21, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/29116772/n-6-allyladenosine-a-new-small-molecule-for-rna-labeling-identified-by-mutation-assay
#6
Xiao Shu, Qing Dai, Tong Wu, Ian R Bothwell, Yanan Yue, Zezhou Zhang, Jie Cao, Qili Fei, Minkui Luo, Chuan He, Jianzhao Liu
RNA labeling is crucial for the study of RNA structure and metabolism. Herein we report N(6)-allyladenosine (a(6)A) as a new small molecule for RNA labeling through both metabolic and enzyme-assisted manners. a(6)A behaves like A and can be metabolically incorporated into newly synthesized RNAs inside mammalian cells. We also show that human RNA N(6)-methyladenosine (m(6)A) methyltransferases METTL3/METTL14 can work with a synthetic cofactor, namely allyl-SAM (S-adenosyl methionine with methyl replaced by allyl) in order to site-specifically install an allyl group to the N(6)-position of A within specific sequence to generate a(6)A-labeled RNAs...
November 15, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29091948/selection-and-validation-of-appropriate-reference-genes-for-quantitative-real-time-pcr-analysis-in-salvia-hispanica
#7
Rahul Gopalam, Sunny D Rupwate, Ajay W Tumaney
Quantitative real-time polymerase chain reaction (qRT-PCR) has become the most popular choice for gene expression studies. For accurate expression analysis, it is pertinent to select a stable reference gene to normalize the data. It is now known that the expression of internal reference genes varies considerably during developmental stages and under different experimental conditions. For Salvia hispanica, an economically important oilseed crop, there are no reports of stable reference genes till date. In this study, we chose 13 candidate reference genes viz...
2017: PloS One
https://www.readbyqxmd.com/read/29080162/determination-of-s-adenosylmethionine-decarboxylase-activity-in-plants
#8
Antonio F Tiburcio, Rubén Alcázar
The synthesis of spermidine, spermine and thermospermine requires the addition of aminopropyl groups from decarboxylated S-adenosyl-methionine (dSAM). The synthesis of dSAM is catalyzed by S-adenosylmethionine decarboxylase. dSAM levels are usually low, which constitutes a rate-limiting factor in the synthesis of polyamines. In this chapter, we provide a protocol for the determination of SAMDC activity in plants through the detection of radiolabelled CO2 released during the SAMDC reaction.
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29020412/emerging-role-of-one-carbon-metabolism-and-dna-methylation-enrichment-on-%C3%AE-containing-gabaa-receptor-expression-in-the-cerebellum-of-subjects-with-alcohol-use-disorders-aud
#9
Eleonora Gatta, James Auta, David P Gavin, Dulal K Bhaumik, Dennis R Grayson, Subhash C Pandey, Alessandro Guidotti
BACKGROUND: Cerebellum is an area of the brain particularly sensitive to the effects of acute and chronic alcohol consumption. Alcohol exposure decreases cerebellar Purkinje cell output by increasing GABA release from Golgi cells onto extrasynaptic α6/δ-containing GABAA receptors located on glutamatergic granule cells. Here, we studied whether chronic alcohol consumption induces changes in GABAA receptor subunit expression and whether these changes are associated with alterations in epigenetic mechanisms via DNA methylation...
August 19, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28973912/structural-basis-underlying-complex-assembly-and-conformational-transition-of-the-type-i-r-m-system
#10
Yan-Ping Liu, Qun Tang, Jie-Zhong Zhang, Li-Fei Tian, Pu Gao, Xiao-Xue Yan
Type I restriction-modification (R-M) systems are multisubunit enzymes with separate DNA-recognition (S), methylation (M), and restriction (R) subunits. Despite extensive studies spanning five decades, the detailed molecular mechanisms underlying subunit assembly and conformational transition are still unclear due to the lack of high-resolution structural information. Here, we report the atomic structure of a type I MTase complex (2M+1S) bound to DNA and cofactor S-adenosyl methionine in the "open" form. The intermolecular interactions between M and S subunits are mediated by a four-helix bundle motif, which also determines the specificity of the interaction...
October 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28955359/purification-and-in-vitro-activity-of-mitochondria-targeted-nitrogenase-cofactor-maturase-nifb
#11
Stefan Burén, Xi Jiang, Gema López-Torrejón, Carlos Echavarri-Erasun, Luis M Rubio
Active NifB is a milestone in the process of engineering nitrogen fixing plants. NifB is an extremely O2-sensitive S-adenosyl methionine (SAM)-radical enzyme that provides the key metal cluster intermediate (NifB-co) for the biosyntheses of the active-site cofactors of all three types of nitrogenases. NifB and NifB-co are unique to diazotrophic organisms. In this work, we have expressed synthetic codon-optimized versions of NifB from the γ-proteobacterium Azotobacter vinelandii and the thermophilic methanogen Methanocaldococcus infernus in Saccharomyces cerevisiae and in Nicotiana benthamiana...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28949991/structural-insights-into-substrate-selectivity-of-ribosomal-rna-methyltransferase-rlmcd
#12
Yiyang Jiang, Fudong Li, Jihui Wu, Yunyu Shi, Qingguo Gong
RlmCD has recently been identified as the S-adenosyl methionine (SAM)-dependent methyltransferase responsible for the formation of m5U at U747 and U1939 of 23S ribosomal RNA in Streptococcus pneumoniae. In this research, we determine the high-resolution crystal structures of apo-form RlmCD and its complex with SAH. Using an in-vitro methyltransferase assay, we reveal the crucial residues for its catalytic functions. Furthermore, structural comparison between RlmCD and its structural homologue RumA, which only catalyzes the m5U1939 in Escherichia coli, implicates that a unique long linker in the central domain of RlmCD is the key factor in determining its substrate selectivity...
2017: PloS One
https://www.readbyqxmd.com/read/28944535/overexpression-of-sbmyb60-in-sorghum-bicolor-impacts-both-primary-and-secondary-metabolism
#13
Erin D Scully, Tammy Gries, Nathan A Palmer, Gautam Sarath, Deanna L Funnell-Harris, Lisa Baird, Paul Twigg, Javier Seravalli, Thomas E Clemente, Scott E Sattler
Few transcription factors have been identified in C4 grasses that either positively or negatively regulate monolignol biosynthesis. Previously, the overexpression of SbMyb60 in sorghum (Sorghum bicolor) has been shown to induce monolignol biosynthesis, which leads to elevated lignin deposition and altered cell wall composition. To determine how SbMyb60 overexpression impacts other metabolic pathways, RNA-Seq and metabolite profiling were performed on stalks and leaves. 35S::SbMyb60 was associated with the transcriptional activation of genes involved in aromatic amino acid, S-adenosyl methionine (SAM) and folate biosynthetic pathways...
September 25, 2017: New Phytologist
https://www.readbyqxmd.com/read/28939775/translesion-synthesis-dna-polymerases-promote-error-free-replication-through-the-minor-groove-dna-adduct-3-deaza-3-methyladenine
#14
Jung-Hoon Yoon, Jayati Roy Choudhury, Jeseong Park, Satya Prakash, Louise Prakash
N3-Methyladenine (3-MeA) is formed in DNA by reaction with S-adenosylmethionine, the reactive methyl donor, and by reaction with alkylating agents. 3-MeA protrudes into the DNA minor groove and strongly blocks synthesis by replicative DNA polymerases (Pols). However, the mechanisms for replicating through this lesion in human cells remain unidentified. Here we analyzed the roles of translesion synthesis (TLS) Pols in the replication of 3-MeA-damaged DNA in human cells. Because 3-MeA has a short half-life in vitro, we used the stable 3-deaza analog, 3-deaza-3-methyladenine (3-dMeA), which blocks the DNA minor groove similarly to 3-MeA...
November 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28923203/epigenetic-silencing-of-mirna-34a-in-human-cholangiocarcinoma-via-ezh2-and-dna-methylation-impact-on-regulation-of-notch-pathway
#15
Hyunjoo Kwon, Kyoungsub Song, Chang Han, Jinqiang Zhang, Lu Lu, Weina Chen, Tong Wu
Aberrant expression and regulation of miRNAs have been implicated in multiple stages of tumorigenic processes. The current study was designed to explore the biological function and epigenetic regulation of miR-34a in human cholangiocarcinoma (CCA). Our data show that the expression of miR-34a is decreased significantly in CCA cells compared with non-neoplastic biliary epithelial cells. Forced overexpression of miR-34a in CCA cells inhibited their proliferation and clonogenic capacity in vitro, and suppressed tumor xenograft growth in severe combined immunodeficiency mice...
October 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28878744/guanidine-n-methylation-by-blsl-is-dependent-on-acylation-of-beta-amine-arginine-in-the-biosynthesis-of-blasticidin-s
#16
Xiankun Wang, Aiqin Du, Guiyang Yu, Zixin Deng, Xinyi He
The peptidyl nucleoside blasticidin S (BS) produced by Streptomyces griseochromogenes was the first non-mercurial fungicide used to prevent rice blast and increasingly used as a selection reagent in transgenic study. Acylation by addition of a leucine residue at the beta amine group of arginine side chain of demethylblasticidin S (DBS) has been proposed as a novel self-resistance to the cytotoxic biosynthetic intermediate. But the resultant product leucyldemethylblasticidin S (LDBS) has not been isolated as a metabolite, and LDBS synthetase activity remained to be demonstrated in S...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28802136/the-role-of-sulfate-in-aerobic-granular-sludge-process-for-emerging-sulfate-laden-wastewater-treatment
#17
Weiqi Xue, Tianwei Hao, Hamish R Mackey, Xiling Li, Richard C Chan, Guanghao Chen
Sulfate-rich wastewaters pose a major threat to mainstream wastewater treatment due to the unpreventable production of sulfide and associated shift in functional bacteria. Aerobic granular sludge could mitigate these challenges in view of its high tolerance and resilience against changes in various environmental conditions. This study aims to confirm the feasibility of aerobic granular sludge in the treatment of sulfate containing wastewater, investigate the impact of sulfate on nutrient removal and granulation, and reveal metabolic relationships in the above processes...
November 1, 2017: Water Research
https://www.readbyqxmd.com/read/28743037/exogenous-applications-of-polyamines-modulate-drought-responses-in-wheat-through-osmolytes-accumulation-increasing-free-polyamine-levels-and-regulation-of-polyamine-biosynthetic-genes
#18
Heba Talat Ebeed, Nemat Mohamed Hassan, Alshafei Mohammed Aljarani
Polyamines (PAs) can improve drought stress tolerance in plants; however, very limited information is available on the mechanism of action of exogenous application by different methods under drought stress in wheat. The present study investigates the mechanism through which seed priming and foliar spraying with PAs protect wheat plants from drought stress. 10 days old wheat seedlings were exposed to drought stress by withholding water alone or with 100 μM PAs solutions (putrescine, Put; spermine, Spm; and mixture of Put and Spm for 10 h seed-priming or three foliar sprays during withholding water...
July 15, 2017: Plant Physiology and Biochemistry: PPB
https://www.readbyqxmd.com/read/28721805/automated-one-pot-radiosynthesis-of-11c-s-adenosyl-methionine
#19
Florencia Zoppolo, Williams Porcal, Patricia Oliver, Eduardo Osvaldo Savio, Henry Engler
BACKGROUND: Glycine-N-methyl transferase is an enzyme overexpressed in some neoplastic tissues. It catalyses the methylation of glycine using S-adenosyl methionine (SAM) as co-enzyme. SAM is involved in a great variety of biochemical processes, including transmethylation reactions. Thus, [11C]SAM could be used to evaluate transmethylation activity in tumours. The only method reported for [11C]SAM synthesis is an enzymatic process with several limitations. We propose a new chemical method to obtain [11C]SAM, through a one-pot synthesis...
July 18, 2017: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/28701466/methionine-synthase-is-localized-to-the-nucleus-in-pichia-pastoris-and-candida-albicans-and-to-the-cytoplasm-in-saccharomyces-cerevisiae
#20
Umakant Sahu, Vinod K H Rajendra, Shankar S Kapnoor, Raghu Bhagavat, Nagasuma Chandra, Pundi N Rangarajan
Methionine synthase (MS) catalyzes methylation of homocysteine, the last step in the biosynthesis of methionine, which is essential for the regeneration of tetrahydrofolate and biosynthesis of S-adenosylmethionine. Here, we report that MS is localized to the nucleus of Pichia pastoris and Candida albicans but is cytoplasmic in Saccharomyces cerevisiae The P. pastoris strain carrying a deletion of the MET6 gene encoding MS (Ppmet6) exhibits methionine as well as adenine auxotrophy indicating that MS is required for methionine as well as adenine biosynthesis...
September 8, 2017: Journal of Biological Chemistry
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