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UVM CMB Purine and Pyrimidine Biosynth Test

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5 Written Questions

5 Matching Questions

  1. Anti Leukemics
  2. Importance of adenosine Deaminase
  3. Ribonucleotide Reductase allosteric effects
  4. Why IMP to AMP uses GTP
  5. Fifth step in Pyrimidine biosynth OPRT
  1. a 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
  2. b this is a way to use biofeedback high GTP means AMP should be formed Low GTP means GMP should be formed
  3. c OPRT takes orotate and PRPP and adds ribose P to make OMP
  4. d 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. e 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

5 Multiple Choice Questions

  1. Committed Step, and an allosteric enzyme

    Using Aspartate Transcarbamoylase, ATCase takes Carbamoyl Phosphate to N-carbamoyl aspartate adding aspartate
  2. using Carbamoyl phosphate synthetase II, CPS II takes CO2 and Glutamine to Carbamoyl phosphate using 2 ATP

    In mitochondria CPS I uses NH4+ as a nitrogen source, this is part of the urea cycle
  3. some discussed earlier
    araC, triphosphate interferes with DNA synthesis
  4. AZT, DDC, ddI
    Used to treat HIV and AIDS
    Triphosphates inhibit retroviral reverse transcriptase
  5. CTP synthetase takes Nitrogen from Glutamine and ATP and makes CTP the base Cytosine with ribose and three phosphates.

5 True/False Questions

  1. Tx of Gout with AllopurinolClinical use of nucleotide analogs usually is restricted to bases and nucleoside since phosphorylated nucleotides are poorly transported into cells

    They rely on tricking cellular or viral enzymes into phosphorylating nucleosides into metabolically active nucleotide forms, or converting bases into nucleotides vis salvage pathways

          

  2. How Methotrexate Mtx anti folate worksrather than directly inhibiting Thymidylate Synthetase TS is inhibits the cyclical production of the methyl donor N5N10 methylene THF

    It does this by inhibiting the enzyme DHFR dihydrofolate reductase. Stopping the reduction of Dihydrofolate to THF, which is a needed substrate for N5N10 methylene THF

          

  3. Other drugs related to nucleotides and nucleotide metabolismAntivirals, acyclovir, Arabinosyladenine araA, for HSV and herpes related viral encephalitis
    Anti retrovirals, AZT, DDC, ddI for HIV
    Anti neoplastics, arabinosylcytosine araC
    Anti Leukemics, 6 mercaptopurin, 6 thiaguanine

          

  4. Folate antagonists as Antibiotics, Trimethoprimis a selective inhibitor of bacterial DHFR, and is often administered with sulfamethoxazole, an inhibitor of THF biosynthesis from folic acid

    This works because folic acid is biosynthesized in bacteria, but is a component of diet in humans

          

  5. De nove purine biosynthesis is expensive, how much and what do we doFor AMP 8 high energy phosphates, 2 Gln, 1 Gly, 2 Asp

    For GMP 7 high energy phosphates, 3 Gln, 1 Gly, 1 Asp

    Thus we Regulate and use salvage pathways to recycle purines

          

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