The diagram shows the pathway for ethanol catabolism in liver. Acetate can be co
ID: 63440 • Letter: T
Question
The diagram shows the pathway for ethanol catabolism in liver. Acetate can be converted to acetyl-CoA for further metabolism by the citric acid cycle.
(a) Ethanol intoxication is often accompanied by lactate acidosis (that is, the accumulation of lactic acid in the bloodstream. Why does ethanol consumption cause the accumulation of lactate?
(b) Methanol is highly toxic because it is catabolized by the pathway shown to formate, which is an inhibitor of mitochondrial respiration. Methanol poisoning can be prevented by administration of an intoxicating dose of ethanol. How does ethanol work as an antidote for methanol poisoning?
Explanation / Answer
Answer a) It is clearly depicted from the given pathway (figure) that NADH is released during the process of ethanol catabolism. Thus, during ethanol intoxification, high concentration of NADH is formed which inhibits gluconeogenesis by preventing the oxidation step of lactate to pyruvate. As a consequences lactate accumulation occurs resulting to lactic acidosis.
Answer b) Alcohol dehydrogenase (ADH) plays a major role in Methanol toxicity. this particular enzyme oxidises methanol to formaldehyde which subsequently oxidised to formic acid, the major toxic metabolite of methanol. Therefore the best way to overcome the toxicity is by targeting the ADH enzyme. Ethanol is competitive substarte for ADH (enzyme have affinity 10-20 times more for ethanol than methanol) and this delays the methanol metabolism til methanol is eleminated from the body by dialysis.