Card Set Information
Mono/dioxygenase, superoxide/hydrogen peroxide removal, P450 action and isozyme, and polymorphism.
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]
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.