liver detox Flashcards
phase 1 detox enzymes
- CYP450
- epoxide hydrolase
- esterases
where is CYPs found
- ALL CELLS except RBC, skeletal muscles
- in endoplasmic reticulum & mitochondria
reactions catalysed by CYP450
- aliphatic hydroxylation
- aromatic hydroxylation
- epoxidation
typical hydroxylation reaction
O2 + XH + NADPH + H+ –> XOH + H2O + NADP
typical epoxidation reaction
O2 + X + NADPH + H+ –> XO + H2O + NADP
adverse effect of epoxides
- highly reactive -> some can form DNA adducts -> DNA mutation -> CANCER
what enzymes in phase 1 cleaves ester bonds and what functional group is formed
esterases, form OH group
requirement for substrates undergoing phase 2 reaction
- presence of functional group (if not must undergo phase 1 first)
types of phase 2 reactions
- Glucuronidation (UGTs)
- Sulphation (SULTs)
- Glutathione conjugation (GSTs)
- Acetylation (NATs)
- Amino-acid conjugation (glycine conjugation)
important reactions of glucuronidation (transfer of glucuronide group from UDP-glucuronic acid to another molecule)
bilirubin + UDP-glucuronic acid -> conj bilirubin + UDP + H2O
what catalyses synthesis of PAPS
- sulphate conjugation -> enzyme SULFOTRANSFERASES
- present in cytosol & golgi membrane
what is glutathione conjugation
- (epoxides/ double bonds) + glutathione -> glutathione conjugate
- then further metabolised to N-acetylcysteine conjugate (mercapturic acid) -> EXCRETED
what undergoes N-acetylation + enzyme that catalyses reaction
- substrates with NH groups
- catalyzed by N-acetyl transferases
what reaction happens in N-acetylation
- X-NH2 + acetyl-coA -> X-NH-COCH3 + coenzyme A
what catalyses glycine conjugation + what functional groups undergo such reactions
- glycine N-acyltransferease
- substrates contain -COOH
