Alcohol Metabolism Flashcards
Where is alcohol metabolised?
The Liver
How is alcohol (Ethanol) metabolised in the liver?
Alcohol oxidised to Acetaldehyde
Acetaldehyde oxidised to Acetate
Acetate then converted into Acetyl CoA
What enzyme oxidises the alcohol/ethanol to Acetaldehyde?
What is the reducing agent that is produced from this reaction?
Acetaldehyde
NAD+ is reduced to NADH
What enzyme oxidises Acetaldehyde to Acetate?
What reducing agent is produced from this reaction?
Aldehyde dehydrogenase
NAD+ is reduced to NADH
What is the toxic intermediate of alcohol metabolism?
Acetaldehyde
This spins the compound that causes the hangover effect
Why is Aldehyde dehydrogenase important in Alcohol metabolism?
It has a low Km so quickly metabolises Acetaldehyde so it doesn’t accumulate and cause LIVER DAMAGE
How does chronic excess alcohol consumption cause changes in liver metabolism?
NAD+ depletes and Excess NADH accumulates
Excess Acetyl CoA
What are the 4 things that chronic excess alcohol consumption can cause?
Lactic acidosis
Gout (Urate crystals accumulate)
Hypoglycaemia
Fatty liver
What are the 2 key changes that occurs as a result of excess chronic alcohol consumption that leads to the 4 problems that chronic alcohol consumption causes?
Decrease in NAD+/NADH ratio
Increased levels of Acetyl CoA
How does chronic alcohol consumption cause lactic acidosis?
Lots of alcohol oxidation causes NAD+ to be depleted
Low NAD+:NADH ratio
Enzyme lactate dehydrogenase needs NAD+ to oxidise lactate back to pyruvate
Lactate accumulates in blood
Causes lactic acidosis
How does excess chronic alcohol consumption cause Gout?
Decreased NAD+/NADH ratio
Lactate can’t be oxidised to Pyruvate by lactate dehydrogenase
Lactate accumulates
Lactate inhibits kidneys ability to excrete uric acid
Urate Crystals accumulate in tissues
Produces gout
How does excess chronic alcohol consumption cause Hypoglycaemia?
Decreased NAD+/NADH ratio
NAD+ needed in Glycerol metabolism (converting Glycerol phosphate to DHAP) so less Glyceraldehyde 3-P produced
Less conversion of lactate into pyruvate
This means less GLUCONEOGENESIS
HYPOGLYCAEMIA
How does excess Chronic alcohol consumption cause a fatty liver?
Increased amount of Acetyl CoA
Increased synthesis of fatty acids and ketone bodies
Increased synthesis of TAGs in liver
Also lack of NAD+ also contributes, B oxidation of fatty acids can’t happen so fatty acids accumulate
What is the name of the drug used to treat alcohol dependance?
Disulfiram
How does Disulfiram treat alcohol dependence?
Inhibits enzyme Aldehyde dehydrogenase
Acetaldehyde accumulates causing hangover effect
Patients will then associate drinking with the awful hangover effect discouraging drinking
