session 6-drug metabolism,paracetemol,alcohol and extra ROS Flashcards
what does NAPQI conjugate with and therefore depleting its levels in hepatocytes?
glutathione
what else does NAPQI do apart from conjugate with glutathione?
causes covalent binding in hepatic proteins, resulting in destruction of liver cells and liver failure occurs…eventually causing death
what is the antidote used to treat an overdose of paracetamol and what does it do?
acetylcysteine replenishes glutathione levels
what is the degradation pathway of alcohol and what enzymes are involved?
alcohol (ethanol)———->acetaldehyde————->acetate
alcohol dehydrogenase aldehyde dehydrogenase
-acetate is the converted into acetyl coA which enters metabolic pathway.
(REMEMBER: dehydrogenase=loss of hydrogen from alcohol. This must mean that NAD+/NADH is involved to pick up the hydrogen)
why does lactic acidosis occur?
- increased NADH levels due to alcohol metabolism
- meaning insufficient NAD+ available for various processes such as fatty acid oxidation and conversion of lactate to pyruvate
- levels of lactate build up in blood (lowers PH)
if paracetamol is taken in toxic dosages, which toxic metabolite accumulates?
NAPQI
what effect does increased levels of lactate have on the kidneys?
- reduces its ability to excrete uric acid
- crystals of urate accumulates in tissues causing GOUT
how does fasting hypoglycaemia become apparent in an alcoholic?
-low NAD+ combined with the livers inability to use lactate and glycerol means that gluconeogenesis cannot occur
what effect does increased levels of lactate have on the kidneys?
- reduces its ability to excrete uric acid
- crystals of urate accumulates in tissues causing GOUT
how does fasting hypoglycaemia become apparent in an alcoholic?
-low NAD+ combined with the livers inability to use lactate and glycerol means that gluconeogenesis cannot occur
what is the consequence on the liver, if acetyl CoA cannot be oxidised in the TCA cycle due to low NAD+/NADH ratio (i.e.low NAD+ levels compared to NADH)?
- acetyl CoA goes into fatty acid and ketone body synthesis
- fatty acids converted to TAGs but cannot be transported due to lack of lipoproteins
- FATTY liver produced
how can you test for liver cell damage?
-increased levels of enzymes in the blood e.g. transaminases
a damaged liver causes a build up in bilirubin levels. What does this lead to? (medical name and following clinical condition)
- hyperbilirubinaemia
- jaundice
what direct effects does alcohol have on the GI tract?
- diarrhoea
- impaired absorption of nutrients
- thiamine deficiency
what syndrome does thiamine deficiency cause?
-Wernicke Korsakoff=mental confusion and unsteady gait (walking)
