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Nucleotide Metabolism
NUCLEOTIDE METABOLISM General Overview • Structure of Nucleotides Pentoses Purines and Pyrimidines Nucleosides Nucleotides • De Novo Purine Nucleotide Synthesis PRPP synthesis 5-Phosphoribosylamine synthesis IMP synthesis Inhibitors of purine synthesis Synthesis of AMP and GMP from IMP Synthesis of NDP and NTP from NMP • Salvage pathways for purines • Degradation of purine nucleotides • Pyrimidine synthesis Carbamoyl phosphate synthesisOrotik asit sentezi • Pirimidin nükleotitlerinin yıkımı • Ribonükleotitlerin deoksiribonükleotitlere dönüşümü Basic functions of nucleotides • They are precursors of DNA and RNA. • They are the sources of activated intermediates in lipid and protein synthesis (UDP-glucose→glycogen, S-adenosylmathionine as methyl donor) • They are structural components of coenzymes (NAD(P)+, FAD, and CoA). • They act as second messengers (cAMP, cGMP). • They play important role in carrying energy (ATP, etc). • They play regulatory roles in various pathways by activating or inhibiting key enzymes. Structures of Nucleotides • Nucleotides are composed of 1) A pentose monosaccharide (ribose or deoxyribose) 2) A nitrogenous base (purine or pyrimidine) 3) One, two or three phosphate groups. Pentoses 1.Ribose 2.Deoxyribose •Deoxyribonucleotides contain deoxyribose, while ribonucleotides contain ribose. •Ribose is produced in the pentose phosphate pathway. Ribonucleotide reductase converts ribonucleoside diphosphate deoxyribonucleotide. Nucleotide structure-Base 1.Purine 2.Pyrimidine •Adenine and guanine, which take part in the structure -
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. -
Deoxyribonucleic Acid Synthesis I. Effect of in Vivo Cyclophosphamide
ICANCER RESEARCH 26 Part 1, 1466-1472,July 1966] Deoxyribonucleic Acid Synthesis I. Effect of in Vivo Cyclophosphamide Treatment on the in Vitro Activity of the Deoxyribonucleic Acid Synthetase System of Sensitive and Resistant Plasmacytomas1 ARTHUR J. TOMISEK, MARTHA BRUCE IRICK, AND PAULA WEDELES ALLAN Kettering'-Meyer Laboratory,2 Southern Research Institute, Birmingham, Alabama Summary term DNA-synthetase. In addition to this measurement of over-all DNA synthetase activity, we used the same experiments We have shown that the in vivo treatment of Fortner plasma- to determine the time course of radioactivity distribution among cytomas with Cyclophosphamide can lead to strong inhibitions of both deoxyribonucleic acid nucleotidyl transferase and thymi- the soluble components of the synthetase reaction mixtures. Our data show that the observed decreases in enzyme activity dylatc kinase activities in the soluble cell fractions. However, in are among the possible consequences of growth inhibition in the allowing only 2 hr for the inhibitor to act, the effect observed on tumor. the transferase was an unexplained stimulation rather than an inhibition. We have also provided some evidence that the inhibition of Materials and Methods growth precedes the inhibition of deoxyribonucleic acid nucleo ENZYME PREPARATION.Fortner hamster plasmacytoma tidyl transferase activity. ("sensitive") (3) and ite cyclophosphamide-resistant subline (12) were used for bilateral s.c. implantation into groups of 6-12 Introduction Golden Syrian hamsters, the animals in each experiment being uniform with respect to commercial subline, sex, and approxi Previous studies in this laboratory have shown that several mate age. On the 12th-14th postimplant day the animals were alkylating agents inhibited the in vivo synthesis of DNA by divided into 2 subgroups, to receive daily i.p. -
On-Demand Synthesis of Phosphoramidites
ARTICLE https://doi.org/10.1038/s41467-021-22945-z OPEN On-demand synthesis of phosphoramidites Alexander F. Sandahl1, Thuy J. D. Nguyen1, Rikke A. Hansen1, Martin B. Johansen 1, Troels Skrydstrup 1,2 & ✉ Kurt V. Gothelf 1,2 Automated chemical synthesis of oligonucleotides is of fundamental importance for the production of primers for the polymerase chain reaction (PCR), for oligonucleotide-based drugs, and for numerous other medical and biotechnological applications. The highly opti- mised automised chemical oligonucleotide synthesis relies upon phosphoramidites as the 1234567890():,; phosphate precursors and one of the drawbacks of this technology is the poor bench stability of phosphoramidites. Here, we report on the development of an on-demand flow synthesis of phosphoramidites from their corresponding alcohols, which is accomplished with short reaction times, near-quantitative yields and without the need of purification before being submitted directly to automated oligonucleotide synthesis. Sterically hindered as well as redox unstable phosphoramidites are synthesised using this methodology and the sub- sequent couplings are near-quantitative for all substrates. The vision for this technology is direct integration into DNA synthesisers thereby omitting manual synthesis and storage of phosphoramidites. 1 Interdisciplinary Nanoscience Center, iNANO, Aarhus University, Aarhus C, Denmark. 2 Department of Chemistry, Aarhus University, Aarhus C, Denmark. ✉ email: [email protected] NATURE COMMUNICATIONS | (2021) 12:2760 | https://doi.org/10.1038/s41467-021-22945-z | www.nature.com/naturecommunications 1 ARTICLE NATURE COMMUNICATIONS | https://doi.org/10.1038/s41467-021-22945-z ynthetic oligonucleotides are essential for a range of dif- includetheuseofmechanochemistry11 or the use of P(V) chemistry Sferent areas and millions of oligonucleotides are synthesized to form the internucleosidic P–Obond12,13. -
Structure and Function Of
8/5/2019 DNA and RNA The Code of Life The Human Genome Project Gene Expression Genetic code The alphabet of the genetic code contains Genes are DNA sequences that encode proteins (the gene product) only four letters (A,T,G,C). Gene expression refers to the process A number of experiments confirmed that the whereby the information contained in genes genetic code is written in 3-letter words, each begins to have effects in the cell. of which codes for particular amino acid. DNA encodes and transmits the genetic A nucleic acid word (3 nucleotide letters) is information passed down from parents to offspring. referred to as a codon. 1 8/5/2019 Nucleic acids Nucleotides Principle information molecule in the Nucleotides are the unit structure of cell. nucleic acids. Nucleotides composed of 3 All the genetic codes are carried out on components: the nucleic acids. Nitrogenous base (A, C, G, T or U) Pentose sugar Nucleic acid is a linear polymer of Phosphate nucleotides Nucleotides Nitrogenous bases There are four nitrogen bases making up four different nucleotides. There are 2 types: Purines(pyoo r-een): Adenine A Two ring structure Purines Adenine (A) and Guanine (G) Guanine G Pyrimidines(pahy-rim-i-deen,): N base Single ring structure Cytosine (C) and Thymine (T) or Uracil (U). Thymine T Pyrimidines Cytosine C 2 8/5/2019 A NUCLEOTIDE Nucleotide bases 1. Phosphate Group 2.3. 5Nitrogen-Carbon BaseSugar 1. Phosphate Group 2. 5-Carbon Sugar (Dexoyribose or Ribose) 3. (Dexoyribose or Ribose) 1. 3. Nitrogen Base 2. 3. Nucleotides, too O 1. -
Genetic Variation in Phosphodiesterase (PDE) 7B in Chronic Lymphocytic Leukemia: Overview of Genetic Variants of Cyclic Nucleotide Pdes in Human Disease
Journal of Human Genetics (2011) 56, 676–681 & 2011 The Japan Society of Human Genetics All rights reserved 1434-5161/11 $32.00 www.nature.com/jhg ORIGINAL ARTICLE Genetic variation in phosphodiesterase (PDE) 7B in chronic lymphocytic leukemia: overview of genetic variants of cyclic nucleotide PDEs in human disease Ana M Peiro´ 1,2, Chih-Min Tang1, Fiona Murray1,3, Lingzhi Zhang1, Loren M Brown1, Daisy Chou1, Laura Rassenti4, Thomas A Kipps3,4 and Paul A Insel1,3,4 Expression of cyclic adenosine monophosphate-specific phosphodiesterase 7B (PDE7B) mRNA is increased in patients with chronic lymphocytic leukemia (CLL), thus suggesting that variation may occur in the PDE7B gene in CLL. As genetic variation in other PDE family members has been shown to associate with numerous clinical disorders (reviewed in this manuscript), we sought to identify single-nucleotide polymorphisms (SNPs) in the PDE7B gene promoter and coding region of 93 control subjects and 154 CLL patients. We found that the PDE7B gene has a 5¢ non-coding region SNP À347C4T that occurs with similar frequency in CLL patients (1.9%) and controls (2.7%). Tested in vitro, À347C4T has less promoter activity than a wild-type construct. The low frequency of this 5¢ untranslated region variant indicates that it does not explain the higher PDE7B expression in patients with CLL but it has the potential to influence other settings that involve a role for PDE7B. Journal of Human Genetics (2011) 56, 676–681; doi:10.1038/jhg.2011.80; published online 28 July 2011 Keywords: cAMP; chronic lymphocytic -
Table S1. List of Genes Up- Or Down-Regulated in H99 When Bound by 18B7
Table S1. List of genes up- or down-regulated in H99 when bound by 18B7. Up-regulated Genes Classification CNF03470: Formate dehydrogenase Metabolism CNC03960: Phosphate transporter, putative Metabolism CND00530: Putative urea transporter Secretion CNA02250: Ammonium transporter MEP1 Secretion CNC06440: Inositol 1-phosphate synthase Metabolism CND03490: Chitin deacetylase-like mannoprotein MP98 Cell wall CNA04560: Hypothetical protein Hypothetical CNF02180: Acetyl-CoA carboxylase, putative Metabolism CNJ00690: Uracil permease, putative Secretion CNF02510: Alcohol dehydrogenase, putative Metabolism CNE04360: Fatty acid synthase, alpha subunit-related Metabolism CNM00180: Cyclohydrolase, putative Metabolism CNL03740: AF540951 catalase isozyme P Stress CNE04370: Fatty acid synthase, beta subunit Metabolism CNA01790: Expressed protein Hypothetical CNA05700: Expressed protein Hypothetical CND03840: Vacuole fusion, non-autophagic-related protein, putative Cell wall CNM00980: Hypothetical protein Hypothetical CNI02420: Uricase (Urate oxidase), putative Metabolism CNJ01090: Xylitol dehydrogenase-related Cell wall CNC03430: Alpha-1,6-mannosyltransferase, putative Cell wall CNF04120: Expressed protein Hypothetical CNB01810: Short chain dehydrogenase, putative Metabolism CNJ01200: Hypothetical protein Hypothetical CNA01160: LSDR putative Metabolism CNH03430: Hypothetical protein Hypothetical CNM02410: Putative proteine disulfate isomerase Housekeeping CNG04200: Alpha-amylase, putative Cell wall CNC00920: NADP-dependent glutamate dehydrogenase Metabolism -
Unless Otherwise Noted, the Content of This Course Material Is Licensed Under a Creative Commons Attribution – Share Alike 3.0 License
Unless otherwise noted, the content of this course material is licensed under a Creative Commons Attribution – Share Alike 3.0 License. Copyright 2007, Robert Lyons. The following information is intended to inform and educate and is not a tool for self-diagnosis or a replacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. You should speak to your physician or make an appointment to be seen if you have questions or concerns about this information or your medical condition. You assume all responsibility for use and potential liability associated with any use of the material. Material contains copyrighted content, used in accordance with U.S. law. Copyright holders of content included in this material should contact [email protected] with any questions, corrections, or clarifications regarding the use of content. The Regents of the University of Michigan do not license the use of third party content posted to this site unless such a license is specifically granted in connection with particular content objects. Users of content are responsible for their compliance with applicable law. Mention of specific products in this recording solely represents the opinion of the speaker and does not represent an endorsement by the University of Michigan. Viewer discretion advised: Material may contain medical images that may be disturbing to some viewers. Formation of PRPP: Phosphoribose pyrophosphate PRPP Use in Purine Biosynthesis: The First Purine: Inosine Monophosphate (folates are involved in this synthesis) Conversion to Adenosine: Conversion to Guanosine: Nucleoside Monophosphate Kinases AMP + ATP <--> 2ADP (adenylate kinase) GMP + ATP <---> GDP + ADP (guanylate kinase) • similar enzymes specific for each nucleotide • no specificity for ribonucleotide vs. -
SUPPY Liglucosexlmtdh
US 20100314248A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2010/0314248 A1 Worden et al. (43) Pub. Date: Dec. 16, 2010 (54) RENEWABLE BOELECTRONIC INTERFACE Publication Classification FOR ELECTROBOCATALYTC REACTOR (51) Int. Cl. (76) Inventors: Robert M. Worden, Holt, MI (US); C25B II/06 (2006.01) Brian L. Hassler, Lake Orion, MI C25B II/2 (2006.01) (US); Lawrence T. Drzal, Okemos, GOIN 27/327 (2006.01) MI (US); Ilsoon Lee, Okemo s, MI BSD L/04 (2006.01) (US) C25B 9/00 (2006.01) (52) U.S. Cl. ............... 204/403.14; 204/290.11; 204/400; Correspondence Address: 204/290.07; 427/458; 204/252: 977/734; PRICE HENEVELD COOPER DEWITT & LIT 977/742 TON, LLP 695 KENMOOR, S.E., PO BOX 2567 (57) ABSTRACT GRAND RAPIDS, MI 495.01 (US) An inexpensive, easily renewable bioelectronic device useful for bioreactors, biosensors, and biofuel cells includes an elec (21) Appl. No.: 12/766,169 trically conductive carbon electrode and a bioelectronic inter face bonded to a surface of the electrically conductive carbon (22) Filed: Apr. 23, 2010 electrode, wherein the bioelectronic interface includes cata lytically active material that is electrostatically bound directly Related U.S. Application Data or indirectly to the electrically conductive carbon electrode to (60) Provisional application No. 61/172,337, filed on Apr. facilitate easy removal upon a change in pH, thereby allowing 24, 2009. easy regeneration of the bioelectronic interface. 7\ POWER 1 - SUPPY|- LIGLUCOSEXLMtDH?till pi 6.0 - esses&aaaas-exx-xx-xx-xx-xxxxixax-e- Patent Application Publication Dec. 16, 2010 Sheet 1 of 18 US 2010/0314248 A1 Potential (nV) Patent Application Publication Dec. -
Central Nervous System Dysfunction and Erythrocyte Guanosine Triphosphate Depletion in Purine Nucleoside Phosphorylase Deficiency
Arch Dis Child: first published as 10.1136/adc.62.4.385 on 1 April 1987. Downloaded from Archives of Disease in Childhood, 1987, 62, 385-391 Central nervous system dysfunction and erythrocyte guanosine triphosphate depletion in purine nucleoside phosphorylase deficiency H A SIMMONDS, L D FAIRBANKS, G S MORRIS, G MORGAN, A R WATSON, P TIMMS, AND B SINGH Purine Laboratory, Guy's Hospital, London, Department of Immunology, Institute of Child Health, London, Department of Paediatrics, City Hospital, Nottingham, Department of Paediatrics and Chemical Pathology, National Guard King Khalid Hospital, Jeddah, Saudi Arabia SUMMARY Developmental retardation was a prominent clinical feature in six infants from three kindreds deficient in the enzyme purine nucleoside phosphorylase (PNP) and was present before development of T cell immunodeficiency. Guanosine triphosphate (GTP) depletion was noted in the erythrocytes of all surviving homozygotes and was of equivalent magnitude to that found in the Lesch-Nyhan syndrome (complete hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency). The similarity between the neurological complications in both disorders that the two major clinical consequences of complete PNP deficiency have differing indicates copyright. aetiologies: (1) neurological effects resulting from deficiency of the PNP enzyme products, which are the substrates for HGPRT, leading to functional deficiency of this enzyme. (2) immunodeficiency caused by accumulation of the PNP enzyme substrates, one of which, deoxyguanosine, is toxic to T cells. These studies show the need to consider PNP deficiency (suggested by the finding of hypouricaemia) in patients with neurological dysfunction, as well as in T cell immunodeficiency. http://adc.bmj.com/ They suggest an important role for GTP in normal central nervous system function. -
Effect of Cytidine on Membrane Phospholipid Synthesis in Rat Striatal Slices
Journal of Neurochemi,enry Raven Press, Ltd ., New York © 1995 International Society for Neurochemistry Effect of Cytidine on Membrane Phospholipid Synthesis in Rat Striatal Slices Vahide Savci and Richard J . Wurtman Delzcartrnent of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, U .S .A . Abstract : Using rat striatal slices, we examined the effect cell culture systems and in vivo experiments, exoge- of cytidine on the conversion of [ 3H]choline to [ 3H]- nous cytidine has been shown to be taken up into cells phosphatidylcholine ([ 3 H]PC), and on net syntheses of and converted sequentially to CMP, CDP, and CTP PC, phosphatidylethanolamine (PE), and phosphatidyl- (Plagemann, 1971a,b ; Trovarelli et al ., 1982 ; 1984 ; serine, when media did or did not also contain choline, Lopez G.-Coviella and Wurtman, 1992) . CTP is re- ethanolamine, or serine . Incubation of striatal slices with quired to form key intermediates in the biosynthesis cytidine (50-500 NM) caused dose-dependent increases in intracellular cytidine and cytidine triphosphate (CTP) of both phosphatidylcholine (PC) and phosphati- levels and in the rate of incorporation of [ 3H]choline into dylethanolamine (PE) (quantitatively the most sig- 3 membrane [ H] PC . In pulse-chase experiments, cytidine nificant phospholipids of eukaryotic cells) via the Ken- (200 N,M) also increased significantly the conversion of nedy pathway (Kennedy and Weiss, 1956 ; Pelech and [ 3H]choline to [ 3 H]PC during the chase period . When Vance, 1984 ; Vance, 1985) and also in the biosynthe- slices were incubated with this concentration of cytidine sis of phosphatidylinositol (Vance, 1985 ; Majerus, for 1 h, small (7%) but significant elevations were ob- 1992 ; Pike, 1992) . -
Standard Abbreviations
Journal of CancerJCP Prevention Standard Abbreviations Journal of Cancer Prevention provides a list of standard abbreviations. Standard Abbreviations are defined as those that may be used without explanation (e.g., DNA). Abbreviations not on the Standard Abbreviations list should be spelled out at first mention in both the abstract and the text. Abbreviations should not be used in titles; however, running titles may carry abbreviations for brevity. ▌Abbreviations monophosphate ADP, dADP adenosine diphosphate, deoxyadenosine IR infrared diphosphate ITP, dITP inosine triphosphate, deoxyinosine AMP, dAMP adenosine monophosphate, deoxyadenosine triphosphate monophosphate LOH loss of heterozygosity ANOVA analysis of variance MDR multiple drug resistance AP-1 activator protein-1 MHC major histocompatibility complex ATP, dATP adenosine triphosphate, deoxyadenosine MRI magnetic resonance imaging trip hosphate mRNA messenger RNA bp base pair(s) MTS 3-(4,5-dimethylthiazol-2-yl)-5-(3- CDP, dCDP cytidine diphosphate, deoxycytidine diphosphate carboxymethoxyphenyl)-2-(4-sulfophenyl)- CMP, dCMP cytidine monophosphate, deoxycytidine mono- 2H-tetrazolium phosphate mTOR mammalian target of rapamycin CNBr cyanogen bromide MTT 3-(4,5-Dimethylthiazol-2-yl)-2,5- cDNA complementary DNA diphenyltetrazolium bromide CoA coenzyme A NAD, NADH nicotinamide adenine dinucleotide, reduced COOH a functional group consisting of a carbonyl and nicotinamide adenine dinucleotide a hydroxyl, which has the formula –C(=O)OH, NADP, NADPH nicotinamide adnine dinucleotide