Alcohol Metabolism Flashcards
Ethanol oxidation pathway
Ethanol–> acetaldehyde via alcohol dehydrogenase, occurs in cytosol; acetaldehyde to acetate via aldehyde dehydrogenase in the mito; acetate to acetyl-CoA via A-CoA synthetase also in the mito
what are the main concerns with alcohol liver disease?
increased production of acetaldehyde and ROS
main damages causes by acetaldehyde
binds to reactive groups (SH, NH2) of proteins and other biomolecules–> decreased protein synth, decreased secretion of serum proteins and VLDL, accumulation of proteins and lipids causing swelling and cell damage;
main damages caused by free rads
lipid peroxidation; GSH is bound by acetaldehyde and oxidizes it–>no defense mech
effects of induction of CYP2E1
- increases ethanol clearance from the blood
- increases production of acetaldehyde
- increases risk for hepatic injury
- acetald. could enter blood and damage other tissues
- CYPs could generate free rads, increasing hepatic injury and leading to cirrhosis
why does too much alcohol cause hypoglycemia?
gluconeogenesis is inhibited because the excess production of NADH favours: pyruvate-->lactate amino acids--> pyruvate --> lactate OAA-->malate glycerol --> Glycerol 3 P
what are the acute effects of alcohol metabolism in the liver
effects on FA metabolism; alcohol-induced ketaoacidosis; lactic acidosis; hypoglycemia in fasting individuals;
how does ethanol induce ketoacidosis
increases A-CoA (because NADH inhibits CAC, and OAA is low since its conversion to malate is favoured)–>increases ketone bodies
what are alcohol’s effects of FA metabolism?
increases in FA–>inhibits beta oxidation, FAs increase in the liver; increase in Glycerol 3 P–>increases TAGs
how does alcohol cause lactic acidosis?
pyruvate to lactate is favoured; lactate + H –> lactic acid–>lactic acidosis–>bad for gout patients!
what are the factors that affect the metabolim of ethanol?
genotype; drinking history; sex; quantity
