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5 Written Questions

5 Matching Questions

  1. Why allopurinal decreases rate of purine biosynthesis
  2. Prokaryotic Regulation of Pyrimidine Biosynth
  3. how 5 fluorouracil FUra works
  4. Biochemical Consequenses of ADA deficiency
  5. How Methotrexate Mtx anti folate works
  1. a rather 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
  2. b it is similar to dUMP and acts as a suicide inhibitor or thymidylate synthetase TS. This kill rapidly dividing cells Tumors and immune cells
  3. c It lowers the PRPP pool by binding and using HGPRT to form an allopurinol ribonucleotide

    This inhibits the action of glutamine PRPP amidotransferase

    and Thus there is less flux through the de novo purine pathway
  4. d CTP inhibits the action of ATCase the committed step and addition of aspartate to carbamoyl P

    and UMP inhibits the action of CPSII the first step and formation of Carbamoyl p
  5. e ADA deficiency causes abnormal build up of Deoxyadenosine containing nucleotides including dATP

    dATP feedback inhibits ribonucleotide reductase, allosterically choking off production of other dNTPs

    Lack of dNTPs prevents DNA synthesis preventing proliferation of lymphocytes.

5 Multiple Choice Questions

  1. ATP and GTP allosterically inhibit formation of PRPP from pentose phosphate pathway

    IMP, AMP and GMP allosterically inhibit PRPP amidotransferase, the committed step of the pathway with adds a N from Glutamine to PRPP

    AMP and GMP allosterically inhibit the first step in their own formation from IMP

    ATP and GTP are require for each others formation a non-allosteric type of biofeedback
  2. Removes CO2 and forms Uracil base on ribose P, UMP from OMP
  3. 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
  4. Purine biosynthesis regulation and secondary causes

    Increased activity of PRPP synthetase increases conc of PRPP

    Increased activity of PRPP amido transferase

    also Partial loss of activity of HGPRT salvage enzyme
  5. Used for salvage

    Hypoxanthine Guanine PRT or HGPRT catalyzes 2 rxns

    PRPP and hypoxanthine to IMP plus PPi

    or PRPP plus Guanine to GMP plus PPi

    Adenine PRT , APRT

    PRPP plus adenine to AMP plus PPi.

5 True/False Questions

  1. GoutElevated levels of Uric Acid, chronic elevation of blood uric acid, hyperuricemia from xanthine overproduction and formation of uric acid

    Also called Gouty arthritis and uric acid nephrophathy

    Uric acid has limited water solubility and precipitates under acidic conditions like collecting ducts eg kidney stones, a can lead to sodium urate that is most likely to precipitate at neutral pH synovial fluid of jointe eg gouty arthritis

          

  2. Other drugs related to nucleotides and nucleotide metabolismUses 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. Important Enzymes in Pyrimidine BiosynthOPRT takes orotate and PRPP and adds ribose P to make OMP

          

  4. Why IMP to GMP uses ATPthis is a way to use biofeedback high ATP means GMP should be formed Low ATP means ATP should be formed

          

  5. Anti Leukemics6 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

          

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