Alcohol i.e. Ethanol,
once absorbed by the body is taken up mostly by the liver and is oxidised to
Acetaldehyde in three different compartments in the cell, by different
enzymes as follows:
Part of liver cell
Conversions aiding the oxidation of EtOH
H2O2 is reduced to H2O
CYP2E1 : MEOS (Microsomal Ethanol Oxidizing System)
NADPH is converted to NADP+
Alcohol Dehydrogenase (ADH)
NAD+ is converted to NADH
This acetaldehyde produced is then converted into Acetate in the mitochondria of the same cell:
When excess alcohol is metabolised, as we can see from the above
reactions, the amount of NADH increases
in the body, which affects various other pathways.
Higher amounts of NADH, inhibits gluconeogenesis by preventing the conversion
of lactate to pyruvate, and instead facilitates the opposite reaction, forming lactate from pyruvate. Higher
amounts of lactic acid in the body leads to Lactic Acidosis and inhibited gluconeogenesis leads to hypoglycaemia.
The conversion of Alanine to pyruvate by a transamination reaction is
also enhanced by increased NADH. This further adds to the pool of increased
Pyruvate and hence lactic acid in the body.
Excess NADH also has an inhibitory effect on the TCA cycle,
leading to altered energy metabolism.
Muscle wasting occurs to compensate for this lack of
energy, which produces Oxaloacetate from
Aspartate. Oxaloacetate is converted
to Malate in presence of excess NADH, which in turn is converted to Pyruvate, and eventually lactate, again leading to
Also, increased levels of
NADH promotes fatty acid biosynthesis,
while inhibiting their ?-oxidation,
which results in steatosis or fatty
This is how ethanol metabolism
leads to perturbations in the metabolic homeostasis of our body.