MEH Alcohol metabolism and oxidative stress Flashcards
Where is most alcohol metabolised in the body?
90% liver
Where does the other 10% go?
Breath
Kidneys
What common molecule does alcohol metabolism form?
Acetyl co A
What is the recommended drinking limits for men and women in UK?
14 units a week over at least 3 days
Why two enzymes are used in alcohol metabolism? Why by produce causes a hangover?
Alcohol dehydrogenase (alcohol to acetyl aldehyde) Aldehyde dehydrogenase (acetyl aldehyde to acetate) Toxic metabolite intermediate acetyl aldehyde responsible for hangover
How is acetate converted to acetyl co A? What happens after that in metabolism?
Bound to co enzyme A
Used in TCA cycle or for fatty acid synthesis
Which metabolite of alcohol can lead to liver damage? What by products of alcohol metabolism can change liver metabolism?
Acetyl aldehyde
NADH and acetyl co A
Alcohol oxidation leads to (increased/decreased) NAD+ and (increased/decreased) acetyl co A?
Alcohol oxidation leads to reduced NAD+ as carrier molecule has taken e-/H+ from oxidation reactions.
Increase in acetyl co A from acetyl aldehyde
What are the the three initial consequences of low NAD+? What is the initial consequence of increased acetyl co A build up?
Reduced NAD+ means less substrate for
- Conversion of lactate to pyruvate
- Metabolism of glycerol
- Fatty acid oxidation
What four consequences can occur as a result of reduced NAD+ for conversion of lactate to pyruvate?
Lactic acidosis
Reduced gluconeogenesis - hypoglycaemia
Urate crystals accumulate in tissues producing gout
Also reduced FA oxidation which adds to fatty liver
How does alcohol excess lead to gout?
Alcohol oxidation causes a decrease in NAD+, so there is less substrate to convert lactate to pyruvate (oxidation), meaning there is a lactate build up. This reduces the kidneys ability to excrete uric acid - uric acid builds up in tissues producing gout
How does alcohol excess lead to hypoglycaemia?
Reduced NAD+ availability due to alcohol oxidation, leads to less substrate for metabolism of glycerol in the liver. So less gluconeogenesis in the liver —> hypoglycaemia
How does alcohol excess lead to lactic acidosis?
Reduced NAD+ due to alcohol oxidation leads to less lactate being converted to pyruvate in the liver. Lactate accumulates –> reduced pH in blood lactic acidosis
What are the three methods that lead to fatty liver in alcohol excess?
Reduced NAD+ due to alcohol oxidation means inadequate NAD+ for fatty acid oxidation –> build up of FA leads to increased TAGs that are stored/deposited in liver.
Also increased acetyl co A from alcohol oxidation from acetyl aldehyde leads to diversion of acetyl co A to form ketone bodies and FA –> increased TAGs
Lower lipoprotein synthesis so fat accumulates as can’t make amino acids/proteins
What can increased acetyl co A from alcohol metabolism lead to?
Increased FA synthesis and ketones —> increased TAG synthesis leading to fatty liver
What is dilsufuram and how is it used?
Is a drug that blocks aldehyde dehydrogenase, so acetyl aldehyde accumulates giving symptoms of hangover.
Is used in conjunct as a therapy for alcoholism