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https://www.readbyqxmd.com/read/28708927/orotidine-containing-rna-implications-for-the-hierarchical-selection-systems-chemistry-emergence-of-rna
#1
Eun-Kyong Kim, Vincent Martin, Ramanarayanan Krishnamurthy
The prebiotic synthesis of canonical nucleobases from HCN is a cornerstone for the RNA world hypothesis. However, their role in the primordial pathways to RNA is still debated. The very same process starting from HCN also gives rise to orotic acid, which (via orotidine) plays a crucial role in extant biology in the de novo synthesis of uridine and cytidine, the informational base-pairs in RNA. However, orotidine itself is absent in RNA. Given the prebiotic and biological relevance of orotic acid vis-à-vis uracil, we investigated orotidine containing RNA oligonucleotides and show that they have severely compromised base-pairing properties...
July 14, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28652707/development-of-new-promising-antimetabolite-dfp-11207-with-self-controlled-toxicity-in-rodents
#2
Masakazu Fukushima, Kenzo Iizuka, Cheng Jin, Chun Zhang, Mei Hong, Kiyoshi Eshima
To reduce 5-fluorouracil (5-FU)-induced serious toxicities without loss of antitumor activity, we have developed DFP-11207, a novel fluoropyrimidine, which consists of 1-ethoxymethyl-5-fluorouracil (EM-FU; a precursor form of 5-FU), 5-chloro-2,4-dihydroxypyridine (CDHP; an inhibitor of 5-FU degradation), and citrazinic acid (CTA; an inhibitor of 5-FU phosphorylation). In vitro studies of DFP-11207 indicated that it strongly inhibited the degradation of 5-FU by dihydropyrimidine dehydrogenase (DPD) in homogenates of the rat liver, and also inhibited the phosphorylation of 5-FU by orotate phosphoribosyltransferase (OPRT) in tumor tissues in a similar magnitude of potency by CDHP and CTA, respectively...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28592010/-clinical-diagnosis-and-treatment-of-three-cases-with-hyperornithinemia-hyperammonemia-homocitrullinuria-syndrome
#3
H Z Guan, Y Ding, D X Li, H Dong, J Q Song, Y Jin, Z J Zhu, L Y Sun, Y L Yang
Objective: To study the clinical characteristics, methods of diagnosis and treatment of hyperornithinemia-hyperammonemia- homocitrullinuria (HHH) syndrome. Method: From July 2011 to August 2016, 3 Chinese patients with HHH syndrome were enrolled in this study. The clinical course, biochemical features, brain MRI findings, and gene mutations were analyzed. Result: The three patients' age at onset of symptoms was 3 months to 7 years, and the age of diagonosis was 3 years and 10 months to 9 years and 10 months...
June 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/28467471/multilocus-sequence-typing-biochemical-and-antibiotic-resistance-characterizations-reveal-diversity-of-north-american-strains-of-the-honey-bee-pathogen-paenibacillus-larvae
#4
Sasiprapa Krongdang, Jay D Evans, Jeffery S Pettis, Panuwan Chantawannakul
Paenibacillus larvae is a Gram positive bacterium and the causative agent of the most widespread fatal brood disease of honey bees, American foulbrood (AFB). A total of thirty-three independent Paenibacillus larvae isolates from various geographical origins in North America and five reference strains were investigated for genetic diversity using multilocus sequence typing (MLST). This technique is regarded to be a powerful tool for epidemiological studies of pathogenic bacteria and is widely used in genotyping assays...
2017: PloS One
https://www.readbyqxmd.com/read/28374713/-the-influence-of-potassium-orotate-on-neocollagenogenesis-in-implantation-of-polypropylene-endoprosthesis-and-polypropylene-combined-with-polylactic-acid-endoprosthesis
#5
S V Ivanov, V A Lazarenko, I S Ivanov, I P Parfenov, A V Tsukanov, D V Tarabrin, E G Ob''edkov
AIM: To study neocollagenogenesis after implantation of polypropylene endoprosthesis and polypropylene combined with polylactic acid endoprosthesis on background of «potassium orotate» administration. MATERIAL AND METHODS: We used two different types of endoprosthesis in the experiment. The first type was made of just polypropylene, the second type was made of polypropylene combined with polylactic acid. Histological examination was performed using polarizing microscopy...
2017: Khirurgiia
https://www.readbyqxmd.com/read/28291252/influence-of-ad-libitum-feeding-of-piglets-with-bacillus-subtilis-fermented-liquid-feed-on-gut-flora-luminal-contents-and-health
#6
Yuyong He, Chunxia Mao, Hong Wen, Zhiyu Chen, Tao Lai, Lingyu Li, Wei Lu, Huadong Wu
Some scholars caution that long-term ad libitum feeding with probiotic fermented food poses potential health risks to baby animals. We conducted a feeding experiment to investigate the influence of ad libitum feeding of pre-and post-weaned piglets with a Bacillus subtilis fermented diet on the gut microbiome, gut metabolomic profiles, bile acid metabolism, proinflammatory cytokines and faecal consistency. Compared with piglets fed a Bacillus subtilis-supplemented pellet diet, piglets fed the Bacillus subtilis fermented liquid diet had lower intestinal bacterial diversity (P > 0...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28286319/establishment-of-crispr-cas9-in-alternaria-alternata
#7
Maximilian Wenderoth, Christoph Pinecker, Benjamin Voß, Reinhard Fischer
The filamentous fungus Alternaria alternata is a potent producer of many secondary metabolites, some of which like alternariol or alternariol-methyl ether are toxic and/or cancerogenic. Many Alternaria species do not only cause post-harvest losses of food and feed, but are aggressive plant pathogens. Despite the great economic importance and the large number of research groups working with the fungus, the molecular toolbox is rather underdeveloped. Gene deletions often result in heterokaryotic strains and therefore, gene-function analyses are rather tedious...
April 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28283349/aav-gene-therapy-corrects-otc-deficiency-and-prevents-liver-fibrosis-in-aged-otc-knock-out-heterozygous-mice
#8
Lili Wang, Peter Bell, Hiroki Morizono, Zhenning He, Elena Pumbo, Hongwei Yu, John White, Mark L Batshaw, James M Wilson
Ornithine transcarbamylase (OTC) deficiency is an X-linked disorder of the urea cycle. Hemizygous males and heterozygous females may experience life-threatening elevations of ammonia in blood and brain, leading to irreversible cognitive impairment, coma, and death. Recent evidence of acute liver failure and fibrosis/cirrhosis is also emerging in OTC-deficient patients. Here, we investigated the long-term consequences of abnormal ureagenesis in female mice heterozygous (Het) for a null mutation in the OTC gene...
April 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28225618/three-pyrimidine-decarboxylations-in-the-absence-of-a-catalyst
#9
Charles A Lewis, Lin Shen, Weitao Yang, Richard Wolfenden
The epigenetic modification of DNA by 5-methylation of cytosine residues can be reversed by the action of the TET family of dioxygenases that oxidize the methyl group to produce 5-carboxycytosine (5caC), which can be converted to cytosine in a final decarboxylation step. Likewise, 5-carboxyuracil (5caU) is decarboxylated to uracil in the last step in pyrimidine salvage. In view of the extreme difficulty of decarboxylating derivatives of orotic acid (6caU), it seemed desirable to establish the rates of decarboxylation of 5caC and 5caU in the absence of a catalyst...
March 14, 2017: Biochemistry
https://www.readbyqxmd.com/read/28205048/mild-orotic-aciduria-in-umps-heterozygotes-a-metabolic-finding-without-clinical-consequences
#10
Saskia B Wortmann, Margaret A Chen, Roberto Colombo, Alessandro Pontoglio, Bader Alhaddad, Lorenzo D Botto, Tatiana Yuzyuk, Curtis R Coughlin, Maria Descartes, Stephanie Grűnewald, Bruno Maranda, Philippa B Mills, James Pitt, Catherine Potente, Richard Rodenburg, Leo A J Kluijtmans, Srirangan Sampath, Emil F Pai, Ron A Wevers, George E Tiller
BACKGROUND: Elevated urinary excretion of orotic acid is associated with treatable disorders of the urea cycle and pyrimidine metabolism. Establishing the correct and timely diagnosis in a patient with orotic aciduria is key to effective treatment. Uridine monophosphate synthase is involved in de novo pyrimidine synthesis. Uridine monophosphate synthase deficiency (or hereditary orotic aciduria), due to biallelic mutations in UMPS, is a rare condition presenting with megaloblastic anemia in the first months of life...
May 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28012135/eicosapentaenoic-acid-enriched-phosphatidylcholine-attenuated-hepatic-steatosis-through-regulation-of-cholesterol-metabolism-in-rats-with-nonalcoholic-fatty-liver-disease
#11
Yanjun Liu, Di Shi, Yingying Tian, Yuntao Liu, Qiping Zhan, Jie Xu, Jingfeng Wang, Changhu Xue
Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. Disturbed cholesterol metabolism plays a crucial role in the development of NAFLD. The present study was conducted to evaluate the effects of EPA-PC extracted from sea cucumber on liver steatosis and cholesterol metabolism in NAFLD. Male Wistar rats were randomly divided into seven groups (normal control group, model group, lovastatin group, low- and high-dose EPA groups, and low- and high-dose EPA-PC groups). Model rats were established by administering a diet containing 1% orotic acid...
February 2017: Lipids
https://www.readbyqxmd.com/read/28011993/putative-orotate-transporter-of-cryptococcus-neoformans-oat1-is-a-member-of-the-ncs1-prt-transporter-super-family-and-its-loss-causes-attenuation-of-virulence
#12
Akio Toh-E, Misako Ohkusu, Kiminori Shimizu, Azusa Takahashi-Nakaguchi, Susumu Kawamoto, Naruhiko Ishiwada, Akira Watanabe, Katsuhiko Kamei
It is well known that 5-fluoroorotic acid (5-FOA)-resistant mutants isolated from wild-type Cryptococcus neoformans are exclusively either ura3 or ura5 mutants. Unexpectedly, many of the 5-FOA-resistant mutants isolated in our selective regime were Ura(+). We identified CNM00460 as the gene responsible for these mutations. Cnm00460 belongs to the nucleobase cation symporter 1/purine-related transporter (NCS1/PRT) super family of fungal transporters, representative members of which are uracil transporter, uridine transporter and allantoin transporter of Saccharomyces cerevisiae...
August 2017: Current Genetics
https://www.readbyqxmd.com/read/27928679/development-of-a-pyre-based-selective-system-for-thermotoga-sp-strain-rq7
#13
Dongmei Han, Zhaohui Xu
To fully unlock the biotechnological potentials of Thermotoga species, this study aimed to expand the genetic toolbox of Thermotoga by developing a new selective system. The developed system was composed of two components: a recipient strain bearing a deletion in its orotate phosphoribosyltransferase gene pyrE and a shuttle vector expressing a heterologous pyrE as the selectable marker. A spontaneous uracil auxotroph, T. sp. strain RQ7-15, was isolated at 70 °C with 2 mg/ml 5-fluoroorotic acid. The mutant carried a 112 bp deletion in pyrE and was a suitable recipient strain...
March 2017: Extremophiles: Life Under Extreme Conditions
https://www.readbyqxmd.com/read/27906623/orotate-orotic-acid-an-essential-and-versatile-molecule
#14
REVIEW
M Löffler, E A Carrey, E Zameitat
Orotate (OA) is well-known as a precursor in biosynthesis of pyrimidines; in mammals it is released from the mitochondrial dihydroorotate dehydrogenase (DHODH) for conversion to UMP by the cytoplasmic UMP synthase enzyme. OA is also a normal part of the diet, being found in milk and dairy products, and it is converted to uridine for use in the pyrimidine salvage pathway predominantly in liver, kidney and erythrocytes. Early research into nutrition identified orotate as "vitamin B13," and its use as a complex with organic cations or metal ions was promulgated in body-building, and in assisting therapies of metabolic syndromes...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27574833/hereditary-orotic-aciduria-and-the-excretion-of-orotidine
#15
William L Nyhan, Jon A Gangoiti
Objective Orotic aciduria and deficiency of uridine monophosphate synthetase have been observed in a patient, studied over 10 years, who had no megaloblastic anemia. Excretion of orotic acid and orotidine were 8.24 and 0.52 mmol/mol of creatinine. The ratio of 15.85 differed appreciably from that of 6 patients reported with no megaloblastic anemia. Methods The analysis of orotidine by gas chromotography mass spectrometry was conducted. Conclusion Patients with orotic aciduria with and without megaloblastic anemia cannot be distinguished by ratio of orotic acid to orotidine...
December 2016: Neuropediatrics
https://www.readbyqxmd.com/read/27370710/elevated-plasma-dihydroorotate-in-miller-syndrome-biochemical-diagnostic-and-clinical-implications-and-treatment-with-uridine
#16
John A Duley, Michael G Henman, Kevin H Carpenter, Michael J Bamshad, George A Marshall, Chee Y Ooi, Bridget Wilcken, Jason R Pinner
BACKGROUND: Miller syndrome (post-axial acrofacial dysostosis) arises from gene mutations for the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH). Nonetheless, despite demonstrated loss of enzyme activity dihydroorotate (DHO) has not been shown to accumulate, but paradoxically urine orotate has been reported to be raised, confusing the metabolic diagnosis. METHODS: We analysed plasma and urine from a 4-year-old male Miller syndrome patient. DHODH mutations were determined by PCR and Sanger sequencing...
September 2016: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/27271695/metabolite-amyloids-a-new-paradigm-for-inborn-error-of-metabolism-disorders
#17
Ehud Gazit
The formation of ordered amyloid assemblies is associated with major human degenerative disorders, including Alzheimer's disease, Parkinson's disease, and type 2 diabetes. Amyloid fibrils are elongated nanoscale structures that bind to specific dyes (including thioflavin T and Congo red). Amyloid fibrillar assemblies or their early intermediates are known to induce apoptotic cytotoxic effect. Until recently, amyloid fiber formation was observed only with proteins and peptides. We reported in 2012 that a single amino acid, phenylalanine, could also form typical amyloid fibrils with the same morphology, dye-binding specificity, and electron diffraction pattern as protein amyloids...
July 2016: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/27147233/hyperammonemia-due-to-adult-onset-n-acetylglutamate-synthase-deficiency
#18
Anne-Els van de Logt, Leo A J Kluijtmans, Marleen C D G Huigen, Mirian C H Janssen
A 59-year-old woman, with a medical history of intellectual disability after perinatal asphyxia, was admitted because of coma due to hyperammonemia after she was treated for a fracture of the pelvis. The ammonia level was 280 μM. Acquired disorders as explanation for the hyperammonemia were excluded. Metabolic investigations showed an elevated glutamine and alanine and low citrulline, suspect for a urea cycle defect (UCD). Orotic acid could not be demonstrated in urine. DNA investigations were negative for mutations or deletions in the OTC and CPS1 gene, but revealed a homozygous c...
2017: JIMD Reports
https://www.readbyqxmd.com/read/26995155/fetal-gene-therapy-for-ornithine-transcarbamylase-deficiency-by-intrahepatic-plasmid-dna-micro-bubble-injection-combined-with-hepatic-ultrasound-insonation
#19
Yoshie Oishi, Takashi Kakimoto, Wenji Yuan, Shuichi Kuno, Hiromasa Yamashita, Toshio Chiba
We evaluated the therapeutic efficacy of hepatic transfection of plasmid DNA using micro-bubbles and ultrasound insonation for fetal correction of ornithine transcarbamylase (OTC) deficiency in mice. Twenty-three sparse-fur heterozygous pregnant mice (day 16 of gestation) were divided into three groups: injection of plasmid-DNA micro-bubble mixture into fetal liver with ultrasound insonation (Tr, n = 11); control group 1 (C1), injection of plasmid-DNA micro-bubble mixture into fetal liver with no insonation (n = 5); and control group 2 (C2), injection of saline-micro-bubble mixture into fetal liver with ultrasound insonation (n = 7)...
June 2016: Ultrasound in Medicine & Biology
https://www.readbyqxmd.com/read/26861612/investigation-of-vital-pathogenic-target-orotate-phosphoribosyltransferases-oprtase-from-thermus-thermophilus-hb8-phylogenetic-and-molecular-modeling-approach
#20
Kanagarajan Surekha, Damodharan Prabhu, Mariadasse Richard, Mutharasappan Nachiappan, Jayashree Biswal, Jeyaraman Jeyakanthan
Biosynthesis pathways of pyrimidine and purine are shown to play an important role in regular cellular activities. The biosynthesis can occur either through de novo or salvage pathways based on the requirement of the cell. The pyrimidine biosynthesis pathway has been linked to several disorders and various autoimmune diseases. Orotate phosphoribosyl transferase (OPRTase) is an important enzyme which catalyzes the conversion of orotate to orotate monophosphate in the fifth step of pyrimidine biosynthesis. Phylogenetic analysis of 228 OPRTase sequences shows the distribution of proteins across different living forms of life...
June 1, 2016: Gene
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