L25 - liver metabolism

remove of substance or termination of it’s biological action

• metabolism • excretion

anabolism (build up) and catabolism (breakdown)

• kidneys excrete urine • the faecal route

• liver • kidneys • lungs

hepatic artery and portal vein

• into bile • but most is reabsorbed into SI

liver enzymes to form polar molecules with can be excreted in urine

• catabolism: oxidation, reduction, hydrolysis • products can be “still” or “even more” reactive • new functional groups (e.g OH) to provide point of conjugation • reaction done by haptic microsomal enzymes on SER inside hepatocytes • microsomal enzymes apart of cytochrome P450 family

• family of haem enzymes • diff members of family have diff letters + numbers • differ in a.a sequence, substrate specificity, susceptibility to inducers + inhibitors • species + inter individual variation

• P450 contains fe3+ • this combines with drug • receives electron from NADPH P450 reductase • iron reduced to fe2+ • combines with O2, a proton, an electron to form FEOOH-DH • this combines with H+ to form h2o and FeO3+DH • this extract H+ ion to release DOH and regenerated P450

• anabolic • involve conjugation (attachment of substituent group) • inactive product • carrier out by liver • hydrophilic conjugates secreted into bile, delivered to SI • where conjugation removed • molecule is reabsorbed - enterohepatic recirculation

• food + drugs entering gut absorbed into SI and pass into blood • blood carried to liver by hepatic portal vein • hepatic microsomal enzymes metabolise food + drugs before they enter systemic circulation

pro drugs - drugs which become active once metabolised by microsomal enzymes

platelet function, it is inflammatory

toxic

• single nucleotide polymorphisms (SNPs) • giving rise to different polymorphic forms which metabolise at different rates

drug becomes toxic or less effective

become active faster:??? not sure if this is right answer

• inducers: brussel sprouts, smoking, wort • inhibitors: grapefruit juice

• drugs can increase activity of CYP enzymes • affecting the metabolism of other compounds/drug

glucuronyl transferase given to premature babies to increase conjugation + remove bilirubin

co administered drugs can be metabolised too quickly reducing effect, toxic metabolites can be increased

highly hepatotoxic