Liver Detoxification Flashcards
Phase 1 of Biotransformation reactions
Functionalization
Non-synthetic, add or expose functional groups
-OH, -SH, -NH2, -COOH
Phase 2 of Biotransformation reactions
Conjugation
Biosynthetic
Conjugation with endogenous molecules, glucuronic acid, sulphate, glutathione.
Covalent bonds formed.
Are glucuronides hydrophilic?
Yes, they are polar molecules
Where does most detoxification take place
The liver
Functions of liver in detoxification
Inactivation and facilitated elimination of drugs and other xenobiotics
Formation of active metabolites with similar activity
Activation of pro-drugs
Toxification of less toxic xenobiotics
The endoplasmic reticulum lining
Is phospholipid
Cytochrome P450 enzymes
Oxidise the substrate and reduce oxygen.
At least 10 main groups.
All are present in the smooth endoplasmic reticulum.
Cytochrome reductases subunit which uses NADPH
Are inducible - certain drugs, dietary components and some environmental toxins cause increased enzyme activity
Generate a reactive free radical compouns
What is a cytochrome?
Redox-active proteins containing a haem, with a central Fe atom at its core, as a cofactor.
Involved in electron transport chain and redox catalysis.
Classified according to type of haem and mode of binding.
Which cytochrome p-450 isoform is involved in metabolism of about 50% of all prescribed drugs?
CYP3A4
(paracetamol, codeine, diazepam, many more!)
Cytochrome P450 reductase
Membrane-bound enzyme required for electron transfer from NADPH to cytochrome P450 and other heme proteins including heme oxygenase in endoplasmic reticulum
The 3 stages of biotransformation and clearance
Phase 1 - Oxidation
Phase 2 - Conjugation
Phase 3 - Elimination
Phase 1 - Oxidation
Cytochrome P450 enzymes promote oxidation and reduction.
Increases water solubility and polarity enabling excretion via urine/ bile
Phase 2 - Conjugation
Involves conjugation with various groups, decreases toxicity of substance
Phase 3 - Elimination
