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UVM CMB Purine and Pyrimidine Biosynth Test

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5 Written Questions

5 Matching Questions

  1. Severe Combined Immunodeficiency Syndrome
  2. Purine Biosynthesis Overview
  3. Importance of adenosine Deaminase
  4. Series of steps for Purine after is PRA
  5. Ribonucleotide Reductase allosteric effects
  1. a Starting point with PRPP, and activated ribose

    Purine ring is built up step by step while attached to ribose sugar

    forming IMP a nucleotide intermediate that can form either AMP or GMP
  2. b ADA deaminates Adenosine to insosine, enabling the salvage pathway of HGPRT to take it to IMP. after the ribose and phosphate are removed by PNP

    if ADA does not work SCIDS develops
  3. c Ribonucleotide Reductase is a heterotatramer with 2 types of subunits

    There are 3 types of binding sites

    C= Catalytic site which binds to substrates A, U, G, CDP

    A= Activity Site, for allosterica regulation, this site regulates whether it is fast or slow. I only binds with ATP or dATP to slow the catalytic rate, high dATP is the stop signal

    S= Specificity Site for Allosteric regulation it binds
    -ATP or dATP to activate reduction of CDP and UDP
    -dTTP to activate reduction of GDP and inhibit production of CDP and UDP
    -dGTP to activate reduction of ADP and inhibit reduction of CDP and UDP
  4. d SCIDS is an Adenosine Deaminase ADA deficiency

    boy in the bubble syndrome, failure of both B and T lymphocytes to proliferate

    all forms inherited, half result from absence of ADA encoded on chromosome 20

    First target for human gene therapy
  5. e PRA adds glycine, enzyme not important

    Methyl group added to N end of glycine with N10 formyl THF

    Glutamine adds N to replace carboxyl oxygen from glycine.

    First 5 point ring closes

    Biotin independent carboxylation with CO2

    Aspartate adds to carboxylated carbon with the N group first

    Fumarate leaves leaving N from Aspartate

    N10 formyl THF methylates lower N

    then there is low energy ring closure

    Makes IMP the base is called hypoxanthine

5 Multiple Choice Questions

  1. high conc of dATP stops the enzyme and other dNTPs are not made
  2. Uses Ribonucleotide Reductase to take A,G,C,UDP to dA,dG,dC,dUDP

    All can form to triphosphate form easily

    Formation of dTMP and dTTP requires Thymidylate Synthetase, which is dependent on THF cycle and dihydrofolate reductase.
  3. some discussed earlier
    araC, triphosphate interferes with DNA synthesis
  4. 6 mercaptopurine
    6 thiaguanine
    These compounds compete with hypoxanthine and guanine for the salvage enzyme HGPRT.
    They are converted by HGPRT into respective ribonucleotides, they inhibit the committed step of de novo purine biosynthesis pathway catalyzed by Gln PRPP amidotransferase, an effect similar to allopurinol
    They are also incorporated into DNA and RNA
  5. UMP plus two ATP becomes UTP

5 True/False Questions

  1. How to take Ribonucleosides from Mono, Di and tri phosphateUses Ribonucleotide Reductase to take A,G,C,UDP to dA,dG,dC,dUDP

    All can form to triphosphate form easily

    Formation of dTMP and dTTP requires Thymidylate Synthetase, which is dependent on THF cycle and dihydrofolate reductase.

          

  2. Tx of Gout with AllopurinolAllopurinol is a suicide inhibitor of xanthine oxidase, because it is similar in configuration to hypoxanthine and it binds tightly to molybdenum in xanthine oxidase.

    Xanthine oxidase takes Hypoxanthine to xanthine and xanthine to uric acid

          

  3. Anti virals, Acyclovir, AraAAcyclovir, used to treat HSV infections, and is converted to triphosphate by enzymes including a viral nucleoside kinase with broad substrate specificity, and interferes with DNA synthesis in infected cells

    AraA tx for herpes related viral encephalitis. this is converted to triphosphates interferes with DNA synthesis, and is deaminated rapidly in vivo by ADA so is sometimes administered with a ADA inhibitor

          

  4. Important Enzymes in Pyrimidine BiosynthFamilial Orotic Aciduria are inherited deficincies in orotate phosphoribosyltrandferase OPRT and or OMP decarboxylase

    These slow the formation of OMP from orotate, and UMP from OMP.

    Signs and symptomes are growth retardation, megaloblastic anemia, crystalline orotate in urine

    Tx effectively by large doses of orally administered uridine

          

  5. Third step in Pyrimidine biosynth DihydroorotaseCTP synthetase takes Nitrogen from Glutamine and ATP and makes CTP the base Cytosine with ribose and three phosphates.

          

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