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5 Written questions

5 Matching questions

  1. Defects in Pyrimidine Biosynthesis
  2. Deoxyribonucleotide dNTP biosynthesis
  3. Third step in Pyrimidine biosynth Dihydroorotase
  4. Results of tx with allopurinal
  5. How to take Ribonucleosides from Mono, Di and tri phosphate
  1. a Ring closure no ATP

    Forms Di hydroorotase

    after NAD+ forms to orotate
  2. b serum urate decraeases
    serum hypoxanthine and xanthine increase, these are more soluble and easily excreted
    Decreases total rate of purine biosynthesis
  3. c 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.
  4. d Adenylate Kinase takes ATP and AMP to 2 ADPs

    nucleoside monophosphate kinases take G,C,UMPs plus ATP to ADP plus G,C,UDPs

    nucleoside diphosphate kinases take G,C,UDPs plus ATP to ADP plus G,C,UTPs

    oxidative phosphorylation takes ADP plus Pi to ATP
  5. e Familial 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 Multiple choice questions

  1. the base on IMP
  2. 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
  3. 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. Elevated 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
  5. 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 True/False questions

  1. Other drugs related to nucleotides and nucleotide metabolismammonia toxicity
    Ornithine transcarbamoylase def
    in both cases carbamoyl P accumulated in liver mitochondria, which enters cytoplasm, which drives overproduction of orotate via the pyrimidine biosynthesis pathway.

          

  2. Ribonucleotid Reductase relates to SCIDS byhigh conc of dATP stops the enzyme and other dNTPs are not made

          

  3. Purine biosynthesis IMP to AMPIMP uses NAD+ and H20 to oxidize and add carboxyl O to bottom left carbon making base xanthine

    Glutamine and ATP needed to replace carboxyl O with N. Forming GMP

          

  4. Lesch-Nyhan Syndromethe base on IMP

          

  5. Fifth step in Pyrimidine biosynth OPRTusing 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