Biochem: drugs and diseases

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  1. Diabetic ketoacidosis
    since diabetic pts can't process gluc, FA broken down for E instead. Results in prod of ketone bodies (acetone, acetoacetic acid, B-hydroxybutyric acid). Contains carboxylic acid group which can release H and lower pH resulting in acidosis.
  2. Alzheimer's
    misfolded amyloid-B protein
  3. Amyotrophic lateral sclerosis (Lou Gehrig's disease)
    misfolded superoxide dismutase
  4. Huntington's disease
    Huntingin gene w/ polyglutamine expansion (trinucleotide repeats)
  5. Parkinson's
    misfolded a-synuclein
  6. TSEs
  7. Type II diabetes
    misfolded islet amylodi polypeptide
  8. Hereditary persistence of Fetal Hemoglobin
    fetal hemoglobin is not terminated at birth bc mutations prevent formation of tertiary DNA helix in fetal Hb gene promoter region (would normally block fetal Hb prot synth in adulthood). Hb produced in adulthood. Hogs oxygen bc has fetal Hb has high affinity.

    Resembles B-thalessemia
  9. Sickle cell anemia
    results from diff mutations in beta-globin gene
  10. a-thalessemia
    caused by defective a-globin genes

    *note: a-globin forms oxygen transporting part of Hb
  11. lactose intolerance
    caused by changes in MCM6 gene
  12. Topoisomerase inhibitors
    bind to topo 1 and DNA complex which prevents DNA re-ligation and causes DNA damage...apoptosis.
  13. Campothecin
    topo I inhibitor

    binds to enz and DNA with H bonds; toxicity is result of SSbreaks into DSbreaks during S phase

    used in rx of colon cancers
  14. Topotecan
    topo I inhibitor
  15. Lamellarin D
    topo I inhibitor
  16. Topoisomerase II inhibitors
    anti-cancer therapies against lymphoid, non-lymphoid leukemia, non-Hodgkins, and Hodgkins lymphomas, testicular, and lung cancers

    binds to and inhibits topo II (catenanes), resulting in accumulation of SS or DS DNA breaks, inhib of DNA replication and transcription...apoptosis
  17. Etoposide
    topo II inhibitor
  18. Amsacrine
    topo II inhibitor
  19. Etoposide phosphate
    topo II inhibitor
  20. Doxorubicin
    topo II inhibitor
  21. Arabinosyl cytosine (AraC)
    DNA pol inhibitor

    converted to tri-phosphate form and acts as a chain terminator; incorp into DNA but does not have a reactive 3'OH
  22. Cisplatin
    DNA damaging agent that cross-links strands or alkylates DNA

    Pt-based chemo drug used to treat cancers. Pt complexes react in vivo, binding to guanines and causing crosslinking of DNA....apoptosis
  23. Novobiocin

    acts as topo inhibitor

    rx methicillin resistant MSRA
  24. Naladixic acid

    topo inhibitor

    rx UTI
  25. Ciproflaxin
    antibiotic, fluoroquinolone

    topo inhibitor agains +/- bacteria
  26. Metronidazole
    antibiotic, affects anaerobic microorganisms

    reduced to cytotoxic intermediate that destabilizes DNA helix
  27. Azidodeoxythymidine (AZT)
    antiretroviral drug

    analog of thymidine that has selectivity for HIV infected cells; results in chain termination
  28. Lamivudine

    analog of cytidine

    inhibits both types of rt of HIV and rt of hep B
  29. Efavirenz

    binds w/in a pocket at an allosteric site near pol active site; distorts catalytical site to block further nucleic acid synth
  30. Acyclovir (acycloguanosine)
    blocks HSV replication

    *contains partial nucleoside structure; incorporated into viral DNA, resulting in chain termination
  31. POMA (paraneoplastic neuropathies) and neurodegenerative diseases
    due to mutation in hnRNP-P2, a prot that binds to pre-mRNA
  32. a/B-thalessemia
    results from mutations in poly A signal; reduced globin chain synth
  33. DVT/PE
    from defects in cleavage site on mRNA which results in overproduction of clotting factor...hypercoagulability
  34. SLE
    due to disorder in splicing

    pts have autoantibody that inhibits RNA splciing
  35. breast and ovarian cancer
    due to defect in alternative splicing of BRCA1 gene
  36. APL
    co-repressor not released unless high amts of ATR, no transcription of genes since co-repressor still present
  37. Burkitt lymphoma
    Myc mRNA has longer half-life than usual; results in unneeded transcription of genes and too much cell growth
  38. Actinomycin D and doxorubicin
    in cancer rx

    • inhib RNA pol by intercalating DNA to inhib transC
    • inhib DNA pol

    more toxic to normal cells than other drugs
  39. a-amanitin
    in poisonous mushrooms

    inhib euk RNA pol II and somewhat RNA pol III
  40. Rifampicin and rifamycin B
    bind to bacterial RNA pol and inhib elongation

    rx tuberculosis

    *if attack bacterial RNA pol, then also effective against mit RNA pols
  41. Leukoencephalopathy w/ VWM or CACH disease
    results from mutations in eiF-2B (used to recycle eiF-2 in euk translation initiation)
  42. Cycloheximide

    inhib elongation in euk
  43. Erythromycin

    inhib translocation in prok
  44. Neomycin

    inhib translation in prok
  45. Puromycin

    resembles 3' end of tyrosyl-tRNA; peptide bond can be formed btw its amino group and carbonyl of peptidyl-tRNA in P site; competes for entry into A site

    terminates peptide chain synth in prok and euk
  46. Ricin

    affects translation in euk
  47. Streptomycin

    affects initiation and elongation inprok
  48. Tetracyclins

    affects AA-tRNA binding in prok
  49. Diphtheria
    contagious, preventable by immunization

    caused by corynebacterium diphtheriae-secrets toxin which has enz that can enter cells

    covalently links ADP ribose to EF-2, which inactivates EF-2 and inhib prot synth
  50. I cell disease
    deficiency in GlcNac-1-P-transferase enz; no manose-6-phosphates on lys enz...not delivered to lysosomes from golgi

    results in build-up of inclusion bodies bc lysosomes cannot degrade their stuff
  51. Familial Hyperproinsulinemia
    equal amts of insulin and abnormally processed proinsulin released into circulation; ind are neither hypoglycemic or diabetic

    due to deficiency in processing enz or mut in cleavage site of pro-insulin molecule
  52. DIPF
    nerve gas, irreversible enz inhib

    reacts w/ Ser side chain on acetylcholine esterase (enz in nerve impulses)

    used in identifying function of Ser 195 in chymotrypsin
  53. TPCK
    substrate analog of chymotrypsin

    binds to active site and irreversibly modifies His 57 residue resulting in inhib

    indicates chymotrypsin function of His 57
  54. Selegiline
    inhib of monoamine oxidase

    binds as a substrate to enz and utilizes enz's own catalytic mech to covalently modify active site...suicide inhibitor

    lowers levels of dopamine (parkinson's) and serotonin (depression)
  55. Penicillin
    irreversible suicide inhibitor of glycopeptide transpeptidase (critical for bact cell wall synth)

    contains B-lactam ring which makes it super reactive
  56. Chronic myeloid leukemia (CML)
    due to a chromosomal translocation that fuses gene for Abl kinase to gene for BCR prot

    Rx by Abl kinase inhibitors
Card Set:
Biochem: drugs and diseases
2011-09-04 15:34:55
drugs diseases biochemistry

MS1/Mod 1: Biochemistry, drugs and diseases covered in lecture
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