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Cytochrome P450 is a ____________ enzyme
Incorporates one O from O2 into substrate.
Incorporates both O from O2 into substrate. Microbes utilize this enzyme for energy (bioremediation).
Oxygenases _______ oxygen to be more ________ by adding ______.
Many rxn's favorable w/ O but slow bc _____________.
Activate, reactive, electron.
High activation energy.
O2 + 1 electron + 1 electron + 1 electron + 1 electron
O2 -> superoxide -> hydrogen peroxide -> hydroxyl radical -> water
Superoxide spontaneously -> _______ sped up by ________.
Hydrogen peroxide, superoxide dismutase.
H2O2 removed by ________ and ________
Catalase and glutathione peroxidase
H2O2 -> O2 + H2O
H202 + 2GSH -> 2H2O + GSSG
Lacking superoxide dismutase, catalase, and glutathione peroxidase causes:
Werner's disease, Lou Gehrig's disease, periodontal disease
Cytochrome P450 has a ___________ group attached to _______
heme prosthetic group, cysteine.
1. Fe(III) -> ________
- 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
Step 5 to Step 6 in cytochrome P450
Hydroxylation at RH
Epoxide formation if double bond
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.
Experiment that showed cytochrome P450 was not a ______________- by pretreating substrates by _________ and ____________.
Single, phenobarbital, 3-methylcholanthrene.
Liver has ____ more activity than kindey/lungs and _____ than skin.
P450 under _________ control
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.
Induce wide spectrum of isozyme. A mixture of polychlorinated biphenyls mimicking PB + 3MC
Binds to water soluble cytoplasmic protein, enters nucleus, binds DNA and stimulates aryl hydrocarbon hydroxylase.
3 isozyme responsible (1A1, 1A2, 1B1)
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.