Cytochrome P450

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Author:
kohaa
ID:
196520
Filename:
Cytochrome P450
Updated:
2013-01-30 00:47:45
Tags:
ETX 103A
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Description:
Mono/dioxygenase, superoxide/hydrogen peroxide removal, P450 action and isozyme, and polymorphism.
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  1. Cytochrome P450 is a ____________ enzyme
    Mono-oxygenase
  2. Mono-oxygenase
    Incorporates one O from O2 into substrate.
  3. Dioxygenase
    Why important?
    Incorporates both O from O2 into substrate. Microbes utilize this enzyme for energy (bioremediation).
  4. Oxygenases _______ oxygen to be more ________ by adding ______.

    Many rxn's favorable w/ O but slow bc _____________.
    Activate, reactive, electron.

    High activation energy.
  5. O2 + 1 electron + 1 electron + 1 electron + 1 electron
    O2 -> superoxide -> hydrogen peroxide -> hydroxyl radical -> water
  6. Superoxide spontaneously -> _______ sped up by ________.
    Hydrogen peroxide, superoxide dismutase.
  7. H2O2 removed by ________ and ________

    reactions?
    Catalase and glutathione peroxidase

    H2O2 -> O2 + H2O

    H202 + 2GSH -> 2H2O + GSSG
  8. Lacking superoxide dismutase, catalase, and glutathione peroxidase causes:
    Werner's disease, Lou Gehrig's disease, periodontal disease
  9. Cytochrome P450 has a ___________ group attached to _______
    heme prosthetic group, cysteine.
  10. 1. Fe(III) -> ________
    2.
    3.
    4.
    5.
    6.
    7.
    • 1. Fe(III)RH substrate binds
    • 2. Reduced by P450 reductase Fe(II)RH
    • 3. O2 binds Fe(III)O2(-)-RH
    • 4. Reduced by P450 reductase Fe(III)O2(-2)-RH
    • 5. +2H to reduce O to water and form fleeting hydroxyl [Fe(III)R. +.OH]
    • 6. Fe(III)R-OH
    • 7. FE(III) + R-OH + H2O
  11. Step 5 to Step 6 in cytochrome P450
    Hydroxylation at RH

    Epoxide formation if double bond
  12. P450 special features (4)
    • 1. Substrate binds before electron accepted to prevent damage.
    • 2. Fe(II)O2 slowly oxidizes to form superoxide.
    • 3. CO has higher affinity and disrupts cycle.
    • 4. P45O reduced with first electron may reduce substrate which may form damaging molecule.
  13. Experiment that showed cytochrome P450 was not a ______________- by pretreating substrates by _________ and ____________.
    Single, phenobarbital, 3-methylcholanthrene.
  14. Liver has ____ more activity than kindey/lungs and _____ than skin.
    7, 50
  15. P450 under _________ control
    Hormonal
  16. Why are some agents target specific (rat vs human example)
    Rat liver dominates biotransformation so it is a major target. Human less prevalent bc most pass liver.
  17. Arochlor
    Induce wide spectrum of isozyme. A mixture of polychlorinated biphenyls mimicking PB + 3MC
  18. 3-methycholanthrene
    Binds to water soluble cytoplasmic protein, enters nucleus, binds DNA and stimulates aryl hydrocarbon hydroxylase.

    3 isozyme responsible (1A1, 1A2, 1B1)
  19. CYP1A1 induction of AhR by 3-MC ligand
    Related structures also bind receptor (polycyclic aromatics).

    TCDD effective at 30,000 lower conc. than 3-MC and longer lived because 3-MC metabolized quickly.
  20. LAST PARAGRAPH
    DO IT

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