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orotic acid

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
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
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
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...
March 2, 2017: Molecular Genetics and Metabolism
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
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...
February 15, 2017: Journal of Inherited Metabolic Disease
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
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...
December 23, 2016: Current Genetics
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
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
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
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
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
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
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
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
Xiuqing Han, Chunhua Liu, Yong Xue, Jingfeng Wang, Changhu Xue, Teruyoshi Yanagita, Xiang Gao, Yuming Wang
We investigated whether fatty liver preceded insulin resistance or vice versa using a long-term orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) model without the confounding effects of obesity and hyperlipidemia and explored the role of the liver in insulin resistance. Male Wistar rats were fed with or without OA supplementation for 30, 60, and 90 days. The NAFLD group showed increased liver lipid at 30, 60, and 90 days; glucose intolerance was noted at 60 and 90 days. Furthermore, partial liver proteins and gene expressions related to upstream signaling of insulin were decreased...
2016: Bioscience, Biotechnology, and Biochemistry
Tamami Haraguchi, Takahiro Uchida, Mai Hazekawa, Miyako Yoshida, Masaki Nakashima, Hotaka Sanda, Takema Hase, Yutaka Tomoda
The purpose of this study was to determine which foods and/or drinks are capable of reducing the bitterness of topiramate when consumed together with the medicine. The inhibitory effects of foods/drinks (yoghurt and nine other foods/drinks) on the bitterness of topiramate (5 mg/mL) were evaluated with a taste sensor using a bitterness-responsive membrane (C00). The effect of topiramate on the taste characteristics of the foods/drinks themselves was also evaluated by taste sensor outputs. The viscosities of the foods/drinks and the influence of the lactic acid and orotic acid components of yoghurt, the most successful of the tested substances in taste masking, on the bitterness of topiramate were also measured...
2016: Chemical & Pharmaceutical Bulletin
Nuno Carvalho, Eduardo Coelho, Luís Gales, Vítor Costa, José António Teixeira, Pedro Moradas-Ferreira
We demonstrated that a Klura3Δ, mutant of the yeast Kluyveromyces lactis is able to produce and secrete into the growth medium considerable amounts of orotic acid. Using yeast extract-peptone-glucose (YPD) based media we optimized production conditions in flask and bioreactor cultures. With cells grown in YPD 5% glucose medium, the best production in flask was obtained with a 1:12.5 ratio for flask: culture volume, 180 rpm, 28°C and 200 mM MOPS for pH stabilization at neutral values (initial culture pH at 8...
June 2016: Journal of Bioscience and Bioengineering
Katsumi Shibata, Nobuya Morita, Tomoyo Kawamura, Ai Tsuji, Tsutomu Fukuwatari
Fatty liver is caused when rats are given orotic acid of the pyrimidine base in large quantities. The lack of B-group vitamins suppresses the biosynthesis of fatty acids. We investigated how orotic acid-induced fatty liver affects the concentrations of liver, blood, and urine B-group vitamins in rats. The vitamin B6 and B12 concentrations of liver, blood, and urine were not affected by orotic acid-induced fatty liver. Vitamin B2 was measured only in the urine, but was unchanged. The liver, blood, and urine concentrations of niacin and its metabolites fell dramatically...
2015: Journal of Nutritional Science and Vitaminology
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