Identification of Leishmania Major UDP-Sugar Pyrophosphorylase
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REDUCTION of PURINE CONTENT in COMMONLY CONSUMED MEAT PRODUCTS THROUGH RINSING and COOKING by Anna Ellington (Under the Directio
REDUCTION OF PURINE CONTENT IN COMMONLY CONSUMED MEAT PRODUCTS THROUGH RINSING AND COOKING by Anna Ellington (Under the direction of Yen-Con Hung) Abstract The commonly consumed meat products ground beef, ground turkey, and bacon were analyzed for purine content before and after a rinsing treatment. The rinsing treatment involved rinsing the meat samples using a wrist shaker in 5:1 ratio water: sample for 2 or 5 minutes then draining or centrifuging to remove water. The total purine content of 25% fat ground beef significantly decreased (p<0.05) from 8.58 mg/g protein to a range of 5.17-7.26 mg/g protein after rinsing treatments. After rinsing and cooking an even greater decrease was seen ranging from 4.59-6.32 mg/g protein. The total purine content of 7% fat ground beef significantly decreased from 7.80 mg/g protein to a range of 5.07-5.59 mg/g protein after rinsing treatments. A greater reduction was seen after rinsing and cooking in the range of 4.38-5.52 mg/g protein. Ground turkey samples showed no significant changes after rinsing, but significant decreases were seen after rinsing and cooking. Bacon samples showed significant decreases from 6.06 mg/g protein to 4.72 and 4.49 after 2 and 5 minute rinsing and to 4.53 and 4.68 mg/g protein after 2 and 5 minute rinsing and cooking. Overall, this study showed that rinsing foods in water effectively reduces total purine content and subsequent cooking after rinsing results in an even greater reduction of total purine content. -
Chapter 23 Nucleic Acids
7-9/99 Neuman Chapter 23 Chapter 23 Nucleic Acids from Organic Chemistry by Robert C. Neuman, Jr. Professor of Chemistry, emeritus University of California, Riverside [email protected] <http://web.chem.ucsb.edu/~neuman/orgchembyneuman/> Chapter Outline of the Book ************************************************************************************** I. Foundations 1. Organic Molecules and Chemical Bonding 2. Alkanes and Cycloalkanes 3. Haloalkanes, Alcohols, Ethers, and Amines 4. Stereochemistry 5. Organic Spectrometry II. Reactions, Mechanisms, Multiple Bonds 6. Organic Reactions *(Not yet Posted) 7. Reactions of Haloalkanes, Alcohols, and Amines. Nucleophilic Substitution 8. Alkenes and Alkynes 9. Formation of Alkenes and Alkynes. Elimination Reactions 10. Alkenes and Alkynes. Addition Reactions 11. Free Radical Addition and Substitution Reactions III. Conjugation, Electronic Effects, Carbonyl Groups 12. Conjugated and Aromatic Molecules 13. Carbonyl Compounds. Ketones, Aldehydes, and Carboxylic Acids 14. Substituent Effects 15. Carbonyl Compounds. Esters, Amides, and Related Molecules IV. Carbonyl and Pericyclic Reactions and Mechanisms 16. Carbonyl Compounds. Addition and Substitution Reactions 17. Oxidation and Reduction Reactions 18. Reactions of Enolate Ions and Enols 19. Cyclization and Pericyclic Reactions *(Not yet Posted) V. Bioorganic Compounds 20. Carbohydrates 21. Lipids 22. Peptides, Proteins, and α−Amino Acids 23. Nucleic Acids ************************************************************************************** -
2'-Deoxyguanosine Toxicity for B and Mature T Lymphoid Cell Lines Is Mediated by Guanine Ribonucleotide Accumulation
2'-deoxyguanosine toxicity for B and mature T lymphoid cell lines is mediated by guanine ribonucleotide accumulation. Y Sidi, B S Mitchell J Clin Invest. 1984;74(5):1640-1648. https://doi.org/10.1172/JCI111580. Research Article Inherited deficiency of the enzyme purine nucleoside phosphorylase (PNP) results in selective and severe T lymphocyte depletion which is mediated by its substrate, 2'-deoxyguanosine. This observation provides a rationale for the use of PNP inhibitors as selective T cell immunosuppressive agents. We have studied the relative effects of the PNP inhibitor 8- aminoguanosine on the metabolism and growth of lymphoid cell lines of T and B cell origin. We have found that 2'- deoxyguanosine toxicity for T lymphoblasts is markedly potentiated by 8-aminoguanosine and is mediated by the accumulation of deoxyguanosine triphosphate. In contrast, the growth of T4+ mature T cell lines and B lymphoblast cell lines is inhibited by somewhat higher concentrations of 2'-deoxyguanosine (ID50 20 and 18 microM, respectively) in the presence of 8-aminoguanosine without an increase in deoxyguanosine triphosphate levels. Cytotoxicity correlates instead with a three- to fivefold increase in guanosine triphosphate (GTP) levels after 24 h. Accumulation of GTP and growth inhibition also result from exposure to guanosine, but not to guanine at equimolar concentrations. B lymphoblasts which are deficient in the purine salvage enzyme hypoxanthine guanine phosphoribosyltransferase are completely resistant to 2'-deoxyguanosine or guanosine concentrations up to 800 microM and do not demonstrate an increase in GTP levels. Growth inhibition and GTP accumulation are prevented by hypoxanthine or adenine, but not by 2'-deoxycytidine. -
Gout: a Low-Purine Diet Makes a Difference
Patient HANDOUT Gout: A Low-Purine Diet Makes a Difference Gout occurs when high levels of uric acid in your blood cause crystals to form and build up around a joint. Your body produces uric acid when it breaks down purines. Purines occur naturally in your body, but you also get them from certain foods and drinks. By following a low-purine diet, you can help your body control the production of uric acid and lower your chances of having another gout attack. Purines are found in many healthy foods and drinks. The purpose of a low-purine diet is to lower the amount of purine that you consume each day. Avoid Beer High-Purine Foods Organ meats (e.g., liver, kidneys), bacon, veal, venison Anchovies, sardines, herring, scallops, mackerel Gravy (purines leach out of the meat during cooking so gravy made from drippings has a higher concentration of purines) Limit Moderate- Chicken, beef, pork, duck, crab, lobster, oysters, shrimp : 4-6 oz daily Purine Foods Liquor: Limit alcohol intake. There is evidence that risk of gout attack is directly related to level of alcohol consumption What Other Dietary Changes Can Help? • Choose low-fat or fat-free dairy products. Studies show that low- or non-fat milk and yogurt help reduce the chances of having a gout attack. • Drink plenty of fluids (especially water) which can help remove uric acid from your body. Avoid drinks sweetened with fructose such as soft drinks. • Eat more non-meat proteins such as legumes, nuts, seeds and eggs. • Eat more whole grains and fruits and vegetables and less refined carbohydrates, such as white bread and cakes. -
A Previously Undescribed Pathway for Pyrimidine Catabolism
A previously undescribed pathway for pyrimidine catabolism Kevin D. Loh*†, Prasad Gyaneshwar*‡, Eirene Markenscoff Papadimitriou*§, Rebecca Fong*, Kwang-Seo Kim*, Rebecca Parales¶, Zhongrui Zhouʈ, William Inwood*, and Sydney Kustu*,** *Department of Plant and Microbial Biology, 111 Koshland Hall, University of California, Berkeley, CA 94720-3102; ¶Section of Microbiology, 1 Shields Avenue, University of California, Davis, CA 95616; and ʈCollege of Chemistry, 8 Lewis Hall, University of California, Berkeley, CA 94720-1460 Contributed by Sydney Kustu, January 19, 2006 The b1012 operon of Escherichia coli K-12, which is composed of tive N sources. Here we present evidence that the b1012 operon seven unidentified ORFs, is one of the most highly expressed codes for proteins that constitute a previously undescribed operons under control of nitrogen regulatory protein C. Examina- pathway for pyrimidine degradation and thereby confirm the tion of strains with lesions in this operon on Biolog Phenotype view of Simaga and Kos (8, 9) that E. coli K-12 does not use either MicroArray (PM3) plates and subsequent growth tests indicated of the known pathways. that they failed to use uridine or uracil as the sole nitrogen source and that the parental strain could use them at room temperature Results but not at 37°C. A strain carrying an ntrB(Con) mutation, which Behavior on Biolog Phenotype MicroArray Plates. We tested our elevates transcription of genes under nitrogen regulatory protein parental strain NCM3722 and strains with mini Tn5 insertions in C control, could also grow on thymidine as the sole nitrogen several genes of the b1012 operon on Biolog (Hayward, CA) source, whereas strains with lesions in the b1012 operon could not. -
Effects of Allopurinol and Oxipurinol on Purine Synthesis in Cultured Human Cells
Effects of allopurinol and oxipurinol on purine synthesis in cultured human cells William N. Kelley, James B. Wyngaarden J Clin Invest. 1970;49(3):602-609. https://doi.org/10.1172/JCI106271. Research Article In the present study we have examined the effects of allopurinol and oxipurinol on thed e novo synthesis of purines in cultured human fibroblasts. Allopurinol inhibits de novo purine synthesis in the absence of xanthine oxidase. Inhibition at lower concentrations of the drug requires the presence of hypoxanthine-guanine phosphoribosyltransferase as it does in vivo. Although this suggests that the inhibitory effect of allopurinol at least at the lower concentrations tested is a consequence of its conversion to the ribonucleotide form in human cells, the nucleotide derivative could not be demonstrated. Several possible indirect consequences of such a conversion were also sought. There was no evidence that allopurinol was further utilized in the synthesis of nucleic acids in these cultured human cells and no effect of either allopurinol or oxipurinol on the long-term survival of human cells in vitro could be demonstrated. At higher concentrations, both allopurinol and oxipurinol inhibit the early steps ofd e novo purine synthesis in the absence of either xanthine oxidase or hypoxanthine-guanine phosphoribosyltransferase. This indicates that at higher drug concentrations, inhibition is occurring by some mechanism other than those previously postulated. Find the latest version: https://jci.me/106271/pdf Effects of Allopurinol and Oxipurinol on Purine Synthesis in Cultured Human Cells WILLIAM N. KELLEY and JAMES B. WYNGAARDEN From the Division of Metabolic and Genetic Diseases, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina 27706 A B S TR A C T In the present study we have examined the de novo synthesis of purines in many patients. -
Role of Uridine Triphosphate in the Phosphorylation of 1-ß-D- Arabinofuranosylcytosine by Ehrlich Ascites Tumor Cells1
[CANCER RESEARCH 47, 1820-1824, April 1, 1987] Role of Uridine Triphosphate in the Phosphorylation of 1-ß-D- Arabinofuranosylcytosine by Ehrlich Ascites Tumor Cells1 J. Courtland White2 and Leigh H. Hiñes Department of Biochemistry, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27103 ABSTRACT potent feedback regulation by dCTP (3-9). The level of dCTP in the cell has been shown to be an important determinant of Pyrimidine nucleotide pools were investigated as determinants of the ara-C action in a variety of cell types (10-12). For example, rate of phosphorylation of l-j9-D-arabinofuranosylcytosine (ara-C) by Harris et al. (10) demonstrated that the sensitivity of several Ehrlich ascites cells and cell extracts. Cells were preincubated for 2 h with 10 MMpyrazofurin, 10 imi glucosamine, 50 MM3-deazauridine, or mouse tumor cell lines to ara-C was inversely proportional to 1 HIMuridine in order to alter the concentrations of pyrimidine nucleo- their cellular dCTP level. In addition, these authors observed tides. Samples of the cell suspensions were taken for assay of adenosine that thymidine enhanced ara-C sensitivity in those cell lines S'-triphosphate (ATP), uridine 5'-triphosphate (IIP), cytidine S'-tn- where there was a depression in dCTP levels but not in those phosphate, guanosine S'-triphosphate, deoxycytidine S'-triphosphate cell lines where thymidine did not alter dCTP pools. Cellular (dCTP), and deoxythymidine S'-triphosphate; then l MM[3H|ara-C was pools of dCTP may also be decreased by inhibitors of the de added and its rate of intrazellular uptake was measured for 30 min. -
Purine Metabolism in the Protozoan Parasite Eimeria Tenella (Hypoxanthine-Xanthine-Guanine Phosphoribosyltransferase/GMP-Agarose Affinity Column/Alopurinol) C
Proc. NatL Acad. Sci. USA Vol. 78, No. 11, pp. 6618-6622, November 1981 Biochemistry Purine metabolism in the protozoan parasite Eimeria tenella (hypoxanthine-xanthine-guanine phosphoribosyltransferase/GMP-agarose affinity column/alopurinol) C. C. WANG AND P. M. SIMASHKEVICH* Merck Institute for Therapeutic Research, Rahway, New Jersey 07065 Communicated by P. Roy Vagelos, June 25, 1981 ABSTRACT Crude extracts of the oocysts ofEimeria tenella, cidia Eimenria tenella, which develops inside the caecal epithe- a protozoan parasite of the coccidium family that develops inside lial cells ofchickens, effectively takes up hypoxanthine and pref- the caecal epithelial cells ofinfected chickens, do not incorporate erentially incorporates label from it into nucleic acids when glycine or formate into purine nucleotides; this suggests lack of grown in cell culture (13, 14). Purine metabolism in this parasite capability for de novo purine synthesis by the parasite. The ex- is particularly interesting in view of the uricotelic metabolism tracts, however, contain high levels of activity of the purine sal- of chickens and the high levels of hypoxanthine known to ac- vage enzymes: hypoxanthine, guanine, xanthine, and adenine cumulate in avian tissues phosphoribosyltransferases and adenosine kinase. The absence of (15). AMP deaminase from the parasite indicates thatE. tenella cannot In this study, we have demonstrated that E. tenella cannot convert AMP to GMP; the latter thus has to be supplied by the perform de novo purine synthesis and examined the detailed hypoxanthine, xanthine, or guanine phosphoribosyltransferase of mechanism of purine salvage. A purine phosphoribosyltrans- the parasite. These three activities are associatedwith one enzyme ferase that uses hypoxanthine and guanine as well as xanthine (HXGPRTase), which has been purified to near homogeneity in as substrates (HXGPRTase) was identified in the parasite. -
Consequences of Methotrexate Inhibition of Purine Biosynthesis in L5178Y Cells'
[CANCER RESEARCH 35, 1427-1432,June 1975] Consequences of Methotrexate Inhibition of Purine Biosynthesis in L5178Y Cells' William M. Hryniuk2 Larry W. Brox,3J. Frank Henderson, and Taiki Tamaoki DepartmentofMedicine, University ofManitoba,and TheManitoba Institute ofCellBiology, Winnipeg,Manitoba [W. M. H.J and CancerResearch Unit (McEachern Laboratory), and DepartmentofBiochemistry, University ofAlberta, Edmonton,Alberta T6G 2E1 [L. W. B.,J. F. H., T. T.J,Canada SUMMARY recently been shown that the cytotoxicity of methotrexate against cultured mouse lymphoma L5178Y cells is in part Addition of 1 @Mmethotrexate to cultures of L5178Y attributable to a “purineless―state(6, 7). Thus, hypoxan cells results in an initial inhibition ofthymidine, uridine, and thine partially prevented the methotrexate-induced inhibi leucine incorporation into acid-insoluble material followed, tion of thymidine, uridine, and leucine incorporation into after about 10 hr. by a partial recovery in the extent of macromolecules and also delayed the loss ofcell viability, as incorporation of these precursors. Acid-soluble adenosine measured by cloning experiments. These studies also triphosphate and guanosine triphosphate concentrations are showed that, during incubation of L5178Y cells with greatly reduced initially, but guanosine triphosphate con methotrexate in the absence of hypoxanthine, incorporation centrations appear to recover partially by 10 hr. Acid of thymidine into DNA was first inhibited but later partially soluble uridine triphosphate and cytidine -
A Path Towards SARS-Cov-2 Attenuation: Metabolic Pressure on CTP Synthesis Rules the Virus Evolution
bioRxiv preprint doi: https://doi.org/10.1101/2020.06.20.162933; this version posted June 21, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-ND 4.0 International license. 1 A path towards SARS-CoV-2 attenuation: metabolic pressure on CTP synthesis rules the virus evolution Zhihua Ou1,2, Christos Ouzounis3, Daxi Wang1,2, Wanying Sun1,2,4, Junhua Li1,2, Weijun Chen2,5*, Philippe Marlière6, Antoine Danchin7,8* 1. BGI-Shenzhen, Shenzhen 518083, China. 2. Shenzhen Key Laboratory of Unknown Pathogen Identification, BGI-Shenzhen, Shenzhen 518083, China. 3. Biological Computation and Process Laboratory, Centre for Research and Technology Hellas, Chemical Process and Energy Resources Institute, Thessalonica 57001, Greece 4. BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, 518083, China. 5. BGI PathoGenesis Pharmaceutical Technology, BGI-Shenzhen, Shenzhen, China. 6. TESSSI, The European Syndicate of Synthetic Scientists and Industrialists, 81 rue Réaumur, 75002, Paris, France 7. Kodikos Labs, Institut Cochin, 24, rue du Faubourg Saint-Jacques Paris 75014, France. 8. School of Biomedical Sciences, Li KaShing Faculty of Medicine, Hong Kong University, 21 Sassoon Road, Pokfulam, Hong Kong. * To whom correspondence should be addressed Tel: +331 4441 2551; Fax: +331 4441 2559 E-mail: [email protected] Correspondence may also be addressed to [email protected] Keywords ABCE1; cytoophidia; innate immunity; Maxwell’s demon; Nsp1; phosphoribosyltransferase; queuine bioRxiv preprint doi: https://doi.org/10.1101/2020.06.20.162933; this version posted June 21, 2020. -
Mechanism of Excessive Purine Biosynthesis in Hypoxanthine- Guanine Phosphoribosyltransferase Deficiency
Mechanism of excessive purine biosynthesis in hypoxanthine- guanine phosphoribosyltransferase deficiency Leif B. Sorensen J Clin Invest. 1970;49(5):968-978. https://doi.org/10.1172/JCI106316. Research Article Certain gouty subjects with excessive de novo purine synthesis are deficient in hypoxanthineguanine phosphoribosyltransferase (HG-PRTase [EC 2.4.2.8]). The mechanism of accelerated uric acid formation in these patients was explored by measuring the incorporation of glycine-14C into various urinary purine bases of normal and enzyme-deficient subjects during treatment with the xanthine oxidase inhibitor, allopurinol. In the presence of normal HG-PRTase activity, allopurinol reduced purine biosynthesis as demonstrated by diminished excretion of total urinary purine or by reduction of glycine-14C incorporation into hypoxanthine, xanthine, and uric acid to less than one-half of control values. A boy with the Lesch-Nyhan syndrome was resistant to this effect of allopurinol while a patient with 12.5% of normal enzyme activity had an equivocal response. Three patients with normal HG-PRTase activity had a mean molar ratio of hypoxanthine to xanthine in the urine of 0.28, whereas two subjects who were deficient in HG-PRTase had reversal of this ratio (1.01 and 1.04). The patterns of 14C-labeling observed in HG-PRTase deficiency reflected the role of hypoxanthine as precursor of xanthine. The data indicate that excessive uric acid in HG-PRTase deficiency is derived from hypoxanthine which is insufficiently reutilized and, as a consequence thereof, catabolized inordinately to uric acid. The data provide evidence for cyclic interconversion of adenine and hypoxanthine derivatives. Cleavage of inosinic acid to hypoxanthine via inosine does […] Find the latest version: https://jci.me/106316/pdf Mechanism of Excessive Purine Biosynthesis in Hypoxanthine-Guanine Phosphoribosyltransferase Deficiency LEIF B. -
Non-Utilization of Radioactive Lodinated Uracil, Uridine, and Orotic Acid by Animal Tissues in Vivo W
Non-utilization of Radioactive lodinated Uracil, Uridine, and Orotic Acid by Animal Tissues in Vivo W. H. PRUSOFF,WL. HOLMES,tANDA. D. WELCH Department of Pharmacology, School of Medicine, Western Reserve University, Cleveland, Ohio) Adenine (1, 6), guanine (1, 3, 5), cytidine (13), lometric localization of brain tumors. Further desoxycytidine (18), thymidine (18), and orotic more, an I'3-labeled oxazine dye had a significant acid (2), can be utilized by certain mammalian or effect in prolonging the life of mice bearing trans ganisms for the synthesis of nucleic acids ; and the planted tumors (19). If an effective and easily syn rate of incorporation of many of these compounds thesized radioactive iodine-labeled compound into the nucleic acids of rapidly growing tissues, could be found, the possibility might be afforded of such as regenerating liver or neoplastic tissues, is the comparable use of compounds labeled with greater than into those of resting tissues (10, 21). eka-iodine (astatine2@), a potent emitter of alpha Although 8-azaguanine is not a naturally occur particles, although this element is prepared with ring compound, evidence that it can be incorpo difficulty and has the inconveniently short half rated to a small extent into mammalian nucleic life of 7.5 hours (12). acids has been presented (16). This analog of gua Three P3-labeled pyrimidines, iodouridine-5- nine markedly inhibited the growth of Tetrahy I'S', iodouracil-5-I'31, and iodoorotic acid-5-P31, mena geleii, a guanine-requiring protozoan, and of were synthesized, and their incorporation into nor certain experimental tumors. Kidder et al.