nucleotide.txt

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Author:
soren101
ID:
29104
Filename:
nucleotide.txt
Updated:
2010-08-22 16:10:07
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nucleotide
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Description:
nucleotide pathways
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  1. CARBAMOYL PHOSPHATE SYNTHETASE II
    Pyrimidine de novo pathway enzyme

    2 ATP + CO2 + Gln --> Carbamoyl Phosphate

    UTP inhibits
  2. ASPARTATE TRANSCARBAMOYLASE
    Pyrimidine de novo pathway enzyme

    CARBAMOYL PHOSPHATE + ASP --> CARBAMOYL ASPARTATE
  3. OROTATE PHOSPHORIBOSYL TRANSFERASE
    Pyrimidine de novo pathway

    OROTATE + PRPP --> OROTIDINE 5'-MONOPHOSPHATE (OMP)

    Part of a protein with 2 active enzymatic properties, including OMP DECARBOXYLASE

    OROTINE ACIDURIA: Block in UTP & CTP production
  4. OMP DECARBOXYLASE
    Pyrimidine de novo pathway enzyme

    OROTIDINE 5'-MONOPHOSPHATE (OMP) --> URIDINE 5'-MONOPHOSPHATE (UMP)

    Ihibited by UMP, CMP
  5. CTP SYNTHETASE
    Pyrimidine de novo pathway enzyme

    UTP + GLUTAMINE --> CTP

    Inhibited by CTP
  6. PRPP SYNTHETASE
    Important enzyme linking sugar to nucleotide metabolism

    RIBOSE 5-PHOSPHATE + ATP --> 5-PHOSPHORIBOSYL-1-PYROPHOSPHATE
  7. PYRIMIDINE METABOLISM LIMITATIONS
    Brain and bone marrow have NO de novo pathway

    Rely on salvage pathway
  8. PYRIMIDINE PHOSPHORIBOSLY TRANSFERASE
    Pyrimidine salvage pathway enzyme

    PYRIMIDINE BASE + PRPP --> PYRIMIDINE 5'-MONOPHOSPHATE
  9. MAJOR DIFFERENCE BETWEEN PYRIMIDINE/PURINE PATHWAYS
    Purine ring is built piece-meal onto the ribose 5'-phosphate, whereas pyrimidine built THEN added to ribose 5'-phosphate after completion
  10. AMIDOPHOSPHORIBOSYL TRANSFERASE
    First enzyme in Purine de novo pathway

    PRPP --> 5-phosphoribosylamine

    IMP, AMP, GMP inhibits: ALL MUST BE PRESENT

    PRPP upregulates PRPP Synthetase
  11. HGPRT
    Purine salvage pathway enzyme

    HYPOXANTHINE OR GUANINE + PRPP --> IMP OR GMP + PPi

    GOUT: Deficiency leads to increase in free purines; leads to increased uric acid production

    PRPP increases leading to upregulated de novo synthesis; leads to increased uric acid production
  12. APRT
    Purine salvage pathway enzyme

    ADENINE + PRPP --> AMP + PPi
  13. IMP
    Important intermediate in purine de novo synthesis

    ATP required for GMP synthesis; GTP required for AMP synthesis
  14. RIBONUCLEOTIDE REDUCTASE
    Converts ribonucleoSIDES to deoxyribonucleosides

    Ribonucleosides MUST be in Diphosphate form (ADP, GDP, CDP, UDP)

    dATP and dGTP inhibit
  15. THYMIDYLATE SYNTHASE
    Synthesis of deoxythymidine monophosphate

    dUDP + METHYLENE THF --> dTDP + DHF

    THF must be regenerated by DIHYDROFOLATE REDUCTASE
  16. THIOREDOXIN REDUCTASE
    Key enzyme in deoxyribonucleoside conversion

    OXIDIZED THIOREDOXIN --> REDUCED THIOREDOXIN
  17. ADENOSINE DEAMINASE (ADA)
    Degrades purines

    AMP --> HYPOXANTHINE

    Leads to increase in uric acid production
  18. XANTHINE OXIDASE (XO)
    Final enzyme in purine degredation pathway that produces uric acid

    HYPOXANTHINE --> XANTHINE --> URIC ACID

    Allopurinol inhibits: think GOUT; Hyperuricemia
  19. GOUT SYMPTOMS
    Acute arthritic inflammatory attacks in joints, causing pain and destruction of connective tissue

    Uric acid stones in kidney, causing nephropathy

    focal urate deposits that are visible (tophi)
  20. GOUT CAUSES
    Rapid tissue turnover (cancer)

    Purine rich diet

    High PRPP SYNTHASE activity leading to upregulated de novo pathway --> uric acid

    Low HGPRT activity leads to less salvaging of purine bases, which get degraded into uric acid

    High PRPP leads to increased de novo pathway --> uric acid

    Low IMP and GMP from salvage pathway --> less feedback inhibition of de novo pathway --> uric acid
  21. GOUT TREATMENTS
    COLCHICINE: pain from acute attack, swelling, inflammation

    PROBENECIDE: increases uric acid excretion from kidneys, works only if renal excretion is low

    ALLOPURINOL: inhibits XO, leads to increased hypoxanthine/xanthine which is very soluble
  22. LESCH-NYHAN DISEASE SYMPTOMS
    Mental retardation

    Severe plasticity

    Severe self-mutilation

    Hyperuricemia -- associated with high morbidity/mortality
  23. LESCH-NYHAN CAUSES
    Complete deficiency in HGPRT

    Deficient dopaminergic neurons -- purines required for synthesis of neurotransmitters

    Can use Allopurinol to treat
  24. SEVERE COMBINED IMMUNODEFICIENCY DISEASE (SCID) SYMPTOMS
    Loss of immune response due to loss of T/B lymphocytes (lymphocytopenia)

    Decreased circulating immunoglobulins

    Chronic infection
  25. SCID CAUSES
    Low ADA leading to increased adenosine and deoxyadenosine

    Low ribonucleotide reductase --> increased nucleosides which are toxic to lymphocytes, inhibition of DNA synthesis
  26. SCID TREATMENTS
    Isolation

    Blood transfusion

    Bone marrow transplant

    Enzyme replacement therapy

    Gene therapy
  27. HEREDITARY OROTIC ACIDURIA SYMPTOMS
    Severe anemia

    Accumulation of orotate or orotidine in serum and excretion of orotate in urine

    Immunodeficiency

    Poor postnatal growth
  28. HEREDITARY OROTIC ACIDURIA CAUSES and TREATMENTS
    Pyrimidine biosynthesis deficit

    Deficient orotate phosphoribosyl transferase and/or orotidylate decarboxylase --> block in UTP and CTP production

    Give uridine or Cytidine (nucleoSIDES) --> inhibits carbamoyl phosphate synthetase II which lowers de novo orotate and improves anemia
  29. 5-FLUOROURACIL (5-FU)
    Anti-cancer drug

    inhibits thymidylate synthesis

    slows DNA replication
  30. HYDROXYUREA (HU)
    Anti-cancer drug

    Inhibits ribonucleatide reductase

    slows DNA replication
  31. 6-MERCAPTOPURINE (6-MP)
    Anti-cancer drug

    Inhibits de novo purine biosynthesis

    Slows DNA replication
  32. METHOTREXATE (MTX)
    Anti-cancer drug

    Inhibits dihydrofolate reductase

    Slows DNA replication
  33. MYCOPHENOLIC ACID
    Prevents graft rejection (purine inhibitor)

    inhibits inosine monophosphate dehydrogenase in rapidly proliferating T/B cells
  34. SULFA DRUGS
    Sulfonamides target bacteria

    Inhibit folic acid synthesis and thus purine synthesis
  35. WHAT INHIBITS THYMIDYLATE SYNTHASE?
    5-FLUOROURACIL (5-FU)


    INHIBITS PRODUCTION OF dTDP
  36. WHAT INHIBITS RIBONYCLEOTIDE REDUCTASE?
    HYDROXYUREA (HU)
  37. WHAT INHIBITS PURINE de novo SYNTHESIS
    6-MERCAPTOPURINE
  38. WHAT INHIBITS DIHYDROFOLATE REDUCTASE?
    METHOTREXATE (MTX)

    INHIBITS dTDP SPECIFICALLY
  39. PURINE DEGRADATION PATHWAY
  40. PYRIMIDINE de novo PATHWAY (PIC)
  41. PURINE de novo PATHWAY (PIC)
  42. DISEASES ASSOCIATED WITH DNA TRANSCRIPTION (PIC)

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