Drug detoxification Flashcards
Microsomal enzymes
Cytochrome P450
Flavin mono-oxygenase
UDP glucoronysltransferase
Non-microsomal enzyme features
Non-specific (phase I and II reactions)
Non-inducible (synthesised continuously regardless of conditions)
Non-microsomal enzymes examples
Protein oxidase Esterase Amidase Conjugases Alcohol dehydrogenase Aldehyde dehydrogenase
Why are lipophillic drugs not effectively removed by the kidney?
They are passively absorbed due to the fact that they can diffuse through cell membranes easily
What is the aim of drug metabolism in the liver?
Make drugs more polar, so they cannot get across membranes and a thus easily excreted
What is the aim of Phase I reactions?
Make drug more hydrophillic so it can be excreted by the kidneys
How do Phase I reactions achieve their aim?
- They add a hydroxyl group to the drug (-OH)
- or: a reactive site that can be used for conjugation/Phase II reactions is introduced or exposed.
What kind of reactions take place in Phase I?
Oxidation
Reduction
Hydrolysis
Oxidation
- Hydroxylation (add -OH)
- Dealkylation (remove -CH side chains)
- Deamination (remove -NH)
- Hydrogen removal
Reduction
Add hydrogen (saturate unsaturated bonds)
Hydrolysis
- Split amide bonds (peptide bond between COOH and NH)
- Split ester bonds (H from COOH is replaced by hydrocarbon)
Which enzyme normally catalyses Phase I functionalisation reactions
Cytochrome P450
How does Cytochrome P450 work?
- Cytochrome P450 reductase is the enzyme required to transfer electrons from NADPH to CYP450
- It contains flavoprotein which in turn consists of FAD and FMN
-
FAD and FMN - electron donors and acceptors …
- FAD = accepts electrons from NADPH
- FMN = electron donor to CYPs
Overall word equation
NADPH …
NADPH + H+ + O2 + R-H ⇒ NADP+ + H2O + R-OH
What kind of reactions are Phase II reactions?
- Synthetic anabolic reactions
- Synthesis: simple → complex
