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https://www.readbyqxmd.com/read/29148771/an-qm-mm-study-of-the-reaction-catalyzed-by-alkyladenine-dna-glycosylase-examination-of-the-substrate-specificity-of-a-dna-repair-enzyme
#1
Stefan A P Lenz, Stacey D Wetmore
Human alkyladenine DNA glycosylase (AAG) functions as part of the base excision repair pathway to excise structurally diverse oxidized and alkylated DNA purines. Specifically, AAG uses a water molecule activated by a general base and a non-specific active site lined with aromatic residues to cleave the N-glycosidic bond. Despite broad substrate specificity, AAG does not target the natural purines (adenine (A) and guanine (G)). Using the ONIOM(QM:MM) methodology, we provide fundamental atomic level details of AAG bound to DNA-containing a neutral substrate (hypoxanthine (Hx)), a non-substrate (G), or a cationic substrate (7-methylguanine (7MeG)), and probe changes in the reaction pathway that occur when AAG targets different nucleotides...
November 17, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/29132796/old-drug-new-indication-olsalazine-sodium-reduced-serum-uric-acid-levels-in-mice-via-inhibiting-xanthine-oxidoreductase-activity
#2
Yanfen Niu, Hongjian Li, Lihui Gao, Hua Lin, Hsiangfu Kung, Marie Chia-Mi Lin, Kwong-Sak Leung, Man-Hon Wong, Wenyong Xiong, Ling Li
Hyperuricemia, a long-term purine metabolic disorder, is a well-known risk factor for gout, hypertension and diabetes. In maintaining normal whole-body purine levels, xanthine oxidase (XOD) is a key enzyme in the purine metabolic pathway, as it catalyzes the oxidation of hypoxanthine to xanthine and finally to uric acid. Here we used the protein-ligand docking software idock to virtually screen potential XOD inhibitors from 3167 approved small compounds/drugs. The inhibitory activities of the ten compounds with the highest scores were tested on XOD in vitro...
October 31, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29132308/effect-of-two-non-synonymous-ecto-5-nucleotidase-variants-on-the-genetic-architecture-of-inosine-5-monophosphate-imp-and-its-degradation-products-in-japanese-black-beef
#3
Yoshinobu Uemoto, Tsuyoshi Ohtake, Nanae Sasago, Masayuki Takeda, Tsuyoshi Abe, Hironori Sakuma, Takatoshi Kojima, Shinji Sasaki
BACKGROUND: Umami is a Japanese term for the fifth basic taste and is an important sensory property of beef palatability. Inosine 5'-monophosphate (IMP) contributes to umami taste in beef. Thus, the overall change in concentration of IMP and its degradation products can potentially affect the beef palatability. In this study, we investigated the genetic architecture of IMP and its degradation products in Japanese Black beef. First, we performed genome-wide association study (GWAS), candidate gene analysis, and functional analysis to detect the causal variants that affect IMP, inosine, and hypoxanthine...
November 13, 2017: BMC Genomics
https://www.readbyqxmd.com/read/29132024/a-hilic-uhplc-ms-ms-untargeted-urinary-metabonomics-combined-with-quantitative-analysis-of-five-polar-biomarkers-on-osteoporosis-rats-after-oral-administration-of-gushudan
#4
Xiao Wu, Yue Huang, Jinghan Sun, Yongqing Wen, Feng Qin, Longshan Zhao, Zhili Xiong
A HILIC-UHPLC-MS/MS untargeted urinary metabonomic method combined with quantitative analysis of five potential polar biomarkers in rat urine was developed and validated, to further understand the anti-osteoporosis effect of Gushudan(GSD) and its mechanism on prednisolone-induced osteoporosis(OP) rats in this study. The metabolites were separated and identified on Waters BEH HILIC (2.1mm×100mm, 1.7μm) column using the Waters ACQUITY™ ultra performance liquid chromatography system (Waters Corporation, Milford, USA) coupled with a Micromass Quattro Micro™ API mass spectrometer (Waters Corp, Milford, MA, USA)...
October 6, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/29131588/kinetic-isotope-effects-and-transition-state-structure-for-hypoxanthine-guanine-xanthine-phosphoribosyltransferase-from-plasmodium-falciparum
#5
Rodrigo G Ducati, Ross S Firestone, Vern L Schramm
Plasmodium falciparum parasites are purine auxotrophs that rely exclusively on the salvage of preformed purines from their human hosts to supply the requirement for purine nucleotides. Hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) catalyzes the freely reversible Mg2+-dependent conversion of 6-oxopurine bases to their respective nucleotides and inorganic pyrophosphate. The phosphoribosyl group is derived from 5-phospho--D-ribosyl 1-pyrophosphate (PRPP). The enzyme from malaria parasites (PfHGXPRT) is essential as hypoxanthine is the major precursor in purine metabolism...
November 13, 2017: Biochemistry
https://www.readbyqxmd.com/read/29130778/lack-of-induced-mutagenesis-in-e-coli-or-human-lymphoblast-cell-line-upon-long-term-sub-culturing-in-medium-from-irradiated-meat
#6
Sachin N Hajare, Jyoti Tripathi, Satyendra Gautam
PURPOSE: Current study was aimed to enhance the confidence of consumers as well as entrepreneurs towards food irradiation program. MATERIALS AND METHODS: In this work, safety of high dose (25 kGy) irradiated meat samples (HDIMS) was ascertained by scoring mutation frequency through a long-term sub-culturing study in Escherichia coli MG1655 cells (ATCC 700926) up to 1500 generations (at 1%), 250 generations (at 5 and 10%) and human lymphoblast thymidine kinase heterozygote (TK6) cell line (ATCC CRL-8015) [at two gene loci, tk(-/+) (thymidine kinase) and hprt(+) (Hypoxanthine Phosphoribosyltransferase)] up to 156 generations using goat meat sample...
November 13, 2017: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/29125988/quantification-of-nitrogenous-bases-dna-and-collagen-type-i-for-the-estimation-of-the-postmortem-interval-in-bone-remains
#7
Cristina Pérez-Martínez, María D Pérez-Cárceles, Isabel Legaz, Gemma Prieto-Bonete, Aurelio Luna
Estimating the postmortem interval (PMI) is an important goal in forensic medicine and continues to be one of the most difficult tasks of the forensic investigator. Few accurate methods exist to determine the time since death of skeletonized human remains due to the great number of intrinsic and external factors that may alter the normal course of postmortem change. The purpose of this research was to assess the usefulness of various biochemical parameters, such as nitrogenous bases (adenine, guanine, purines, cytosine, thymine, pyrimidines, hypoxanthine and xanthine), DNA and Collagen Type I peptides to estimate PMI...
November 4, 2017: Forensic Science International
https://www.readbyqxmd.com/read/29115578/characterization-of-prostate-cancer-cell-progression-in-zebrafish-xenograft-model
#8
Wei Xu, Brittany A Foster, Mackenzie Richards, Kenneth R Bondioli, Girish Shah, Christopher C Green
Early diagnosis of prostate cancer (PCa) is critical for the application of efficient treatment to PCa patients. However, the majority of PCas remains indolent from several months to several years before malignancy. Current diagnosis methods have limitations in their reliability and are inefficient in time cost. Thus, an efficient in vivo PCa cell xenograft model is highly desired for diagnostic studies in PCas. In the present study we present a standardized procedure to create a PCa cell xenograft model using zebrafish (Danio rerio) as the host...
November 6, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29099052/urinary-metabolomic-profiling-to-identify-potential-biomarkers-for-the-diagnosis-of-behcet-s-disease-by-gas-chromatography-time-of-flight-mass-spectrometry
#9
Joong Kyong Ahn, Jungyeon Kim, Jiwon Hwang, Juhwan Song, Kyoung Heon Kim, Hoon-Suk Cha
Diagnosing Behcet's disease (BD) is challenging because of the lack of a diagnostic biomarker. The purposes of this study were to investigate distinctive metabolic changes in urine samples of BD patients and to identify urinary metabolic biomarkers for diagnosis of BD using gas chromatography/time-of-flight-mass spectrometry (GC/TOF-MS). Metabolomic profiling of urine samples from 44 BD patients and 41 healthy controls (HC) were assessed using GC/TOF-MS, in conjunction with multivariate statistical analysis...
November 2, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29093325/inhibition-of-3-5-2-4-tetrahydroxychalcone-on-production-of-uric-acid-in-hypoxanthine-induced-hyperuricemic-mice
#10
Yanfen Niu, Yuanfang Zhou, Hua Lin, Li-Hui Gao, Wenyong Xiong, Huajie Zhu, Cheng-Gang Zou, Ling Li
The mechanism of 3,5,2',4'-tetrahydroxychalcone on lowing urate level is still unknown. Here we investigated the effects of 3,5,2',4'-tetrahydroxychalcone on urate levels, xanthine oxidase/xanthine dehydrogenase (XOD/XDH) activities in hypoxanthine-induced hyperuricemic mice, as well as the effects of 3,5,2',4'-tetrahydroxychalcone on the mRNA expression levels and content of phosphoribosyl pyrophosphate synthetase (PRPS), phosphoribosyl pyrophosphate amidotransferase (PRPPAT) and hypoxanthine-guanine phosphoribosyl transferase (HGPRT)...
November 1, 2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/29090559/-liver-metabonomics-of-acute-gouty-arthritis-treated-by-diosocorea-nipponica
#11
Shu-Min Liu, Ning Zhang, Dong-Hua Yu, Yu Wang, Qi Zhou, Fang Lu
To explore the prevention and protection effect of Diosocorea nipponica (DNM)) on acute gouty arthritis (AGA) rats based on liver metabonomics, and find potential biomarkers and related pathways. AGA model rats were induced by monosodium urate crystal suspension. UPLC-TOF-MS coupled with pattern recognition technique was employed to find out the potential biomarkers and related metabolic pathways. Eleven common potential biomarkers were identified. Among the potential intervention targets in normal rats given by DNM, 4 biomarkers were up-regulated, and the other 4 targets were down regulated...
May 2017: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
https://www.readbyqxmd.com/read/29079593/hypoxia-modulates-the-purine-salvage-pathway-and-decreases-red-blood-cell-and-supernatant-levels-of-hypoxanthine-during-refrigerated-storage
#12
Travis Nemkov, Kaiqi Sun, Julie A Reisz, Anren Song, Tatsuro Yoshida, Andrew Dunham, Matthew J Wither, Richard O Francis, Robert C Roach, Monika Dzieciatkowska, Stephen C Rogers, Allan Doctor, Anastasios Kriebardis, Marianna Antonelou, Issidora Papassideri, Carolyn Young, Tiffany Thomas, Kirk C Hansen, Steven L Spitalnik, Yang Xia, James C Zimring, Eldad A Hod, Angelo D'Alessandro
Hypoxanthine catabolism in vivo is potentially dangerous as it fuels production of urate and, most importantly, hydrogen peroxide. However, it is unclear whether accumulation of intracellular and supernatant hypoxanthine in stored RBC units is clinically relevant for transfused recipients. Leukoreduced RBCs from G6PD-normal or -deficient human volunteers were stored in AS-3 under normoxic, hyperoxic, or hypoxic conditions (with SO2 ranging from <3 to >95%). RBCs from healthy human volunteers were also collected at sea level or after 1-7 days at high altitude (>5000m)...
October 27, 2017: Haematologica
https://www.readbyqxmd.com/read/29073050/prebiotic-stereoselective-synthesis-of-purine-and-noncanonical-pyrimidine-nucleotide-from-nucleobases-and-phosphorylated-carbohydrates
#13
Hyo-Joong Kim, Steven A Benner
According to a current "RNA first" model for the origin of life, RNA emerged in some form on early Earth to become the first biopolymer to support Darwinism here. Threose nucleic acid (TNA) and other polyelectrolytes are also considered as the possible first Darwinian biopolymer(s). This model is being developed by research pursuing a "Discontinuous Synthesis Model" (DSM) for the formation of RNA and/or TNA from precursor molecules that might have been available on early Earth from prebiotic reactions, with the goal of making the model less discontinuous...
October 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29057475/erding-formula-in-hyperuricaemia-treatment-unfolding-traditional-chinese-herbal-compatibility-using-modern-pharmaceutical-approaches
#14
Jieyu Zuo, Hongming He, Zhengyun Zuo, Nádia Bou-Chacra, Raimar Löbenberg
OBJECTIVES: Traditional Chinese herbal formulas are difficult to be understood because of complex compositions and specific therapeutic principles. To better understand herbal compatibility in Traditional Chinese medicine (TCM), this study was conducted to investigate the effects of a Chinese pharmacopoeia-listed formula, Erding Formula (EF) and its constituent herbs for a new indication, hyperuricaemia. METHODS: A hypoxanthine and potassium oxonate-induced hyperuricemic mouse model, a xylene-induced inflammatory mouse model and an acetic acid-induced pain model were used to test the effects of EF and its constituent herbs...
October 23, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/29056891/polygala-tenuifolia-extract-inhibits-lipid-accumulation-in-3t3-l1-adipocytes-and-high-fat-diet-induced-obese-mouse-model-and-affects-hepatic-transcriptome-and-gut-microbiota-profiles
#15
Chun-Chung Wang, Jui-Hung Yen, Yi-Cheng Cheng, Chia-Yu Lin, Cheng-Ta Hsieh, Rung-Jiun Gau, Shu-Jiau Chiou, Hwan-You Chang
Obesity, the excessive accumulation of lipids in the body, is closely associated with many prevalent human disorders. Continued efforts to identify plant extracts that exhibit anti-obesity effects have drawn much attention. This study investigated whether a Polygala tenuifolia extract (PTE) possesses anti-obesity activity and how PTE may affect liver gene expression and gut microbiota. We used 3T3-L1 adipocytes and a high-fat diet-induced obese mouse model to determine the effects of PTE on lipid accumulation...
2017: Food & Nutrition Research
https://www.readbyqxmd.com/read/29038055/serum-and-brain-purine-levels-in-an-experimental-systemic-infection-of-mice-by-cryptococcus-neoformans-purinergic-immunomodulatory-effects
#16
Maria Isabel de Azevedo, Aleksandro S Da Silva, Laerte Ferreiro, Pedro H Doleski, Alexandre A Tonin, Emerson A Casali, Cesar E J Moritz, Gabriel H Schirmbeck, Valesca V Cardoso, Mariana M Flores, Rafael Fighera, Janio M Santurio
The aim of this study was to evaluate the purine levels in serum and brains of mice experimentally infected by Cryptococcus neoformans. Twenty-four mice were divided into the following groups: a control group (n = 12; Group A) and an infection group with animals that were infected (n = 12; Group B) with a 0.3-mL intraperitoneal injection containing 1.7 × 10(7)C. neoformans cells. Blood and brains were collected on days 20 (n = 6 per group) and 50 (n = 6 per group) post-infection (PI). Histopathology and lung and brain cultures were performed to confirm fungal infection and tissue injuries...
October 14, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/29037708/the-effects-of-edible-chitosan-based-coatings-on-flavor-quality-of-raw-grass-carp-ctenopharyngodon-idellus-fillets-during-refrigerated-storage
#17
Dawei Yu, Yanshun Xu, Joe M Regenstein, Wenshui Xia, Fang Yang, Qixing Jiang, Bin Wang
This study investigated the effects of chitosan-based coatings on flavor retention of refrigerated grass carp fillets by using various indicators: free amino acids (FAA), nucleotides, trimethylamine (TMA), volatile profile, sensory quality, and electronic nose analysis. The results indicated that chitosan-based coatings contributed to the significant reduction of off-flavor compounds, such as TMA, hypoxanthine (Hx) and histidine, and accumulation of inosine monophosphate (IMP) and umami-associated FAA. GC-MS analysis showed 23 volatile organic compounds, including many C5-C9 aldehydes and alcohols in the fresh fillets...
March 1, 2018: Food Chemistry
https://www.readbyqxmd.com/read/29024251/enzymatic-incorporation-of-modified-purine-nucleotides-in-dna
#18
Rania Abu El Asrar, Lia Margamuljana, Mikhail Abramov, Omprakash Bande, Stefano Agnello, Miyeon Jang, Piet Herdewijn
A series of nucleotide analogues, with a hypoxanthine base moiety (8-amino-hypoxanthine, 1-methyl-8-amino-hypoxanthine and 8-oxo-hypoxanthine) together with 5-methyl-isocytosine were tested as potential pairing partners of N8-glycosylated nucleotides with an 8-azaguanine and 8-aza-9-deazaguanine base moiety, using DNA polymerases (incorporation studies). The best results were obtained with the 5-methyl-isocytosine nucleotide followed by the 1-metyl-8-amino-hypoxanthine nucleotide. The experiments demonstrate that a) small differences in the structure (8-azaguanine versus 8-aza-9-deazaguanine) might lead to significant differences in recognition efficiency and selectivity b) base pairing via Hoogsteen recognition, at the polymerase level is possible c) 8-aza-9-deazaguanine represents a self-complementary base pair and d) a correlation exists between the in vitro incorporation studies and in vivo recognition by natural bases in Escherichia coli, but this recognition is not absolute (exceptions are observed)...
October 11, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28992566/quantification-of-xanthine-and-uric-acid-related-compounds-in-urine-using-a-dilute-and-shoot-technique-coupling-ultra-high-performance-liquid-chromatography-and-high-resolution-orbitrap-mass-spectrometry
#19
Adrian Rodriguez, Rosa Maria Gomila, Gabriel Martorell, Antonia Costa-Bauza, Felix Grases
Quantitative analysis of relevant metabolites in biofluids such as urine is often a tedious procedure, since it usually requires extraction, purification or preconcentration. For instance, in the analysis of methylxanthines in urine, a solid-phase extraction is often required. In the current work, a rapid and highly sensitive "dilute-and-shoot" method combining ultra-high-performance liquid chromatography and high-resolution mass spectrometry (UHPLC/HRMS) was validated for urinary determination of twelve analytes: uric acid, hypoxanthine, xanthine, 1-methyluric acid, 1,3-dimethyluric acid, 1-methylxanthine, 3-methylxanthine, 7-methylxanthine, theophylline, theobromine, paraxanthine and caffeine...
November 1, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28976243/colonic-thioguanine-pro-drug-investigation-of-microbiome-and-novel-host-metabolism
#20
Timothy Florin, Ramya Movva, Jakob Begun, John Duley, Iulia Oancea, Páraic Ó Cuív
Thiopurines are analogues of endogenous purines. They are pro-drugs which require the purine salvage pathway to convert them to the active drug nucleotides (TGN). These drugs are used to maintain clinical remission in patients with inflammatory bowel diseases. In our recent Gut paper, we showed that thioguanine worked quickly to improve colitis in the absence in the host animal of the key guanine salvage enzyme, hypoxanthine-guanine-phosphoribosyltransferase (HPRT). Current evidence favours the proposition that active drug delivery to the host lacking HPRT requires translocation of TGN-loaded bacteria across the inflamed mucosal barrier, and most likely delivery by phagocytosis...
October 4, 2017: Gut Microbes
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