M104 Alcohol metabolism symposia Flashcards
Approximately what percentage of ingested ethanol is lost through breath/urine?
10%
the rest is metabolised
Is ethanol commonly found in adipose tissue?
no, very little
Where does the metabolism of ingested ethanol occur?
liver (nearly all)
brain, pancreas and stomach
What is the role of alcohol dehydrogenase?
it converts ethanol to acetaldehyde
Where does the conversion of ethanol to acetaldehyde occur?
in the cytosol of hepatic cells
What is the role of aldehyde dehydrogenase?
to convert acetaldehyde into acetate
Where does the conversion of acetaldehyde into acetate occur?
in the hepatic mitochondria
What happens to the acetate and some of the acetaldehyde in the hepatic mitochondria?
they are released into the circulation
What substances are responsible for the conversion of
ethanol to acetaldehyde?
Cytochrome P450 complexes, particularly CYP2E1 in the mitochondria
catalases (peroxisomes)
Why do chronic drinkers build up tolerance?
bc CYPs are inducible, so the more a person drinks, the more CYP2E1 is expressed and allows more metabolism of the alcohol
What is the CYP2E1 complex involved in?
paracetamol metabolism - converts paracetamol to a toxic intermediate, NAPQI
Why are chronic drinkers more susceptible to the effects of paracetamol toxicity?
bc CYP2E1 is expressed more in chronic drinkers, and it converts paracetamol to a toxic intermediate
NAPQI
What is responsible for people’s bodies having different capacities for processing alcohol?
bc people have different concentrations of alcohol dehydrogenase, which is the first enzyme catalysing the conversion of ethanol to acetaldehyde
What is an example of a group of people that process alcohol differently to others?
individuals of Asian descent who have the B2 ADH isoform metabolise alcohol 20% faster than those who possess the B1 isoforms, which is present in Northern Europeans
What is the isoform responsible for some Asian people metabolising alcohol differently to northern EU’s?
the B2 ADH isoform
What is the role of polymorphisms?
they affect how efficiently acetaldehyde is able to be cleared
Why might some people with certain polymorphisms have different tolerances to the effects of alcohol?
certain polymorphisms will result in the build up of acetaldehyde is responsible for some of the toxic effects of alcohol
What are some of the toxic effects of alcohol?
nausea, vomiting and headaches
What is an effect on the body caused by acetaldehyde build up?
flushing
What might be an effect in people who have less efficient ALD enzymes?
they may have a distaste for alcohol
What is the effect of the alcohol dehydrogenase and aldehyde dehydrogenase reactions on the redox state?
NAD is reduced to NADH
What ratios are increased when the amount of NADH and alcohol metabolised increases?
the lactate : pyruvate ratio
the beta-hydroxybutyrate : acetoacetate ratio
What is the relationship between the metabolism of alcohol and the amount of NADH produced?
the more metabolised alcohol there is, the higher proportion of NADH there is
Why does an increase in metabolised alcohol result in a higher proportion of NADH?
the conversion of ethanol to acetaldehyde and the conversion of acetaldehyde to acetate are coupled to the reduction of the cellular NAD+ to generate NADH
What processes are decreased when the amount of NADH and alcohol metabolised increases?
Glycolysis
Citric acid cycle – ketogenesis
FA oxidation
Gluconeogenesis
What happens when the amount of NADH and alcohol metabolised increases?
the redox potential of the cells is changed
What toxic effect is caused by alcohol on a cellular level?
oxidant stress
What are the effects of oxidant stress on a cellular level?
acute tissue damage and fibrosis is associated with lipid peroxidation
the FRs attack cellular and mitochondrial DNA, causing deletion mutations and genomic instability
What does the metabolic pathway of methanol have in common with that of ethanol?
it uses the same enzymes but it generates different intermediates
What are the stages of the metabolic pathway of methanol?
methanol (+ alcohol dehydrogenase) < formaldehyde (+ aldehyde dehydrogenase) < formic acid (+ folate) < CO2 + H2O