Alcohol metabolism Flashcards
what are the 2 primary pathways of ethanol metabolism?
alcohol dehydrogenase pathway
MEOS- microsomal ethanol oxidizing system
where is the alcohol dehydrogenase step located?
cytoplasm
where is the acetylaldehyde dehydrogenase step located?
mitochondria
what are the 2 steps of the alcohol dehydrogenase pathway?
alcohol dehydrogenase
acetylaldehyde dehydrogenase
in the alcohol dehydrogenase pathway, the liver converts ethanol to?
acetylaldehyde and then to acetate
both acetylaldehyde and acetate produce what?
2 NADH
what are toxic levels of alcohol?
50-100mg/dl
when alcohol dehydrogenase becomes saturated what happens?
we turn to the 2nd pathway MEOS
what is the microsomal ethanol oxidizing system associated with in the cell?
endoplasmic reticulum
what enzymes are associated with the MEOS?
cytochrome P450 system
when ethanol converts into acetylaldehyde it requires?
NADPH
In the MEOS when ethanol is converted into acetylaldehyde, what is produced and what can’t be produced?
free radicals are produced
NADH can not be produced
some enzymes of MEOS are “inducible” what does this mean?
ethanol in high concentrations can induce the synthesis of these enzymes resulting in hepatocytes being able to metabolize ethanol more effectively
what do we convert acetylaldehyde to acetate, what pathway is used?
same as ADH pathway but with acetaldehyde dehydrogenase
acetaldehyde is 30x more toxic than ethanol and both ADH and MEOS produce it. What happens when toxicity happens
attaches covalently to proteins creating protein adducts; if protein is an enzyme it may be impaired
what causes perivenular fibrosis?
acetaldehyde toxicity
acetate increases acetyl CoA which increases ketogenesis which also increases
acidity, FA synthesis and increased acetaldehyde because ADH is inhibited
MEOS needs NADPH but MEOS creates free radicals so NADPH can’t be used for?
regeneration with glutathione which leads to oxidative stress
both alcohol metabolism pathways produce NADH, accumulation of NADH alters?
energy metabolism of the liver; shift toward reduction reactions
more NADH =
less fat burning
more fat synthesis and TAG
Kreb’s inhibition
more lactic acid
lipids accumulate in most tissues where ethanol is metabolized leading to?
fatty liver fatty myocardium fatty renal tubules increased lipid synthesis decreased lipid removal
what are the metabolic effects of alcohol metabolism?
krebs inhibited decreased fat burning fat accumulation lactate accumulation decreased GNG, increased ketogenesis decreased retinoic acid
why does ethanol metabolism effect Vit A absorption?
vit A needs to be converted into retinoic acid and the same enzymes needed for this conversion are what are used for ethanol metabolism
ethanol is competitive inhibitor
which enzyme in ethanol metabolism can become saturated?
alcohol dehydrogenase
