NADH is generated in the first two reactions of alcohol metabolism as outlined above. It is necessary for NADH to then be reoxidised to NAD+ so that it can be involved in further oxidation reactions in the cytosol:
The cytosolic NADH is reoxidised by the mitochondrial electron transport system, so substrate shuttles need to be used to transport the H atoms to the mitochondria.
Under some conditions, the rate of transfer of H atoms by these shuttles is less than the rate of NADH generation, so that the concentration of NAD + becomes greatly reduced. This low concentration of NAD + also restricts the conversion of lactate to pyruvate in the liver. This is one element by which alcohol increases the concentration of lactate in the blood.
The low NAD+ level limits the rate of ethanol oxidation by alcohol dehydrogenase (the first step in alcohol metabolism). Alcohol decreases the ratio of NAD + to NADH within the hepatocyte while it is being oxidised.
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