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5 Written questions

5 Matching questions

  1. Ribonucleotide Reductase allosteric effects
  2. 7th step addition of two phosphates to UMP
  3. Folate antagonists as Antibiotics, Trimethoprim
  4. how 5 fluorouracil FUra works
  5. Pyrimidine Synthesis Differences from Purines
  1. a Unbranched pathway
    Pyrimidine ring synthesized first then attached to ribose phosphate
  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 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 UMP plus two ATP becomes UTP
  5. e is 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 Multiple choice questions

  1. some discussed earlier
    araC, triphosphate interferes with DNA synthesis
  2. 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
  3. serum urate decraeases
    serum hypoxanthine and xanthine increase, these are more soluble and easily excreted
    Decreases total rate of purine biosynthesis
  4. Thymidylate Synthetase uses N5N10 Methylene THF as a methyl transfer group to turn dUMP to dTMP, then becomes DHF which must be recycled
  5. 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 True/False questions

  1. Sites of feedback regulation of Purine biosynthesisCTP inhibits two enzymes

    CTPS which forms CTP from UTP is inhibited by CTP, also it requires GTP so low GTP will slow CTP formation

    CPS II is the first reaction which forms carbamoyl P, and is inhibited by CTP

          

  2. Purine Biosynthesis OverviewStarting 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. Nucleoside PhosphorylasesClinical 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

          

  4. Origins of Pyrimidine Ring AtomsFamilial 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. Severe Combined Immunodeficiency SyndromeSigns and Symptoms young with hematuria, megaloblastic anemia, hyperuricemia, crystals in urine, mental retardation, decreased gross motor function, and self mutilation, gout in early 20s

    is a Rare X linked disorder 1/400000 males, milder form = 8% kelly-seegmiller syndrome

    Cause = near total deficiency of HGPRT about 2% of activity

    biochemical consequenses
    Overproduction or urate
    Elevated PRPP concentrations
    Marked increase in rate of de novo purine biosynth

          

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