- Alcohol is metabolized in the liver by alcohol dehydrogenase and acetaldehyde dehydrogenase. When too much alcohol is consumed, these enzymes can become saturated, leading to a buildup of the toxic acetaldehyde. - Acetaldehyde can damage biomolecules and tissues like neurons. It is also responsible for many of alcohol's effects. A buildup can cause nausea and vomiting and Asian flush syndrome in some people. - Consuming too much alcohol increases fatty acid biosynthesis and cholesterol synthesis, which can lead to fatty liver disease. It also increases NADH levels and decreases NAD+, altering metabolism and potentially causing issues like lactic acidosis, hypoglycemia, and fatty deposits in tissues.

2. • Alcohol, ie. Ethanol is a drug. It has high
energy content, yielding about 7.1 kcal/g on
oxidation.
• Liver is the major site of ethanol oxidation.
• 5% alcohol absorbed in mouth and esophagus
and 95% in portal circulation and from here,
goes to the liver, where alcohol gets
metabolized.

4. • Alcohol dehydrogenase (cytoplasmic enzyme) has
higher affinity for alcohol, means km value low.
• So, if a person drinks too much alcohol, all the
enzymes gets saturated and ethanol is not
converted to acetyl coA and there is
accumulation of acetylaldehyde.
• Now, acetylaldehyde gets out from the cytoplasm
into blood and from blood, they enter into tissues
of any kind, especially neurons.
• Effect of alcohol is mainly based on the action of
acetylaldehyde.

5. • Acetylaldehyde is toxic molecule and damage
most of the biomolecules in our body, i.e.
DNA/RNA/ proteins.
• And when acetylaldehyde is converted into
acetyl- coA and also NAD is converted into
NADH+H, alters all the metabolism in cells and
shortage of NAD.
• Some of the acetate is converted into the acetyl-
coA with the help of enzyme acetyl-coA
synthetase and some of the acetate in blood goes
to the peripheral tissues where it is converted
into acetyl-coA.

6. • And this acetyl-coA is used for energy
purpose/ fatty acid biosynthesis/ cholesterol
synthesis.
• If a person takes too much alcohol, fatty acid
biosynthesis and cholesterol synthesis
increases and it gives rise to fatty liver disease.
• If there is deficient of enzyme acetylaldehyde
dehyrogenase, there is accumulation of
acetylaldehyde, which can be toxic and give
rise to nausea and vomiting and called as
Asian flush syndrome.
• Mostly seen in Chinese and Korean.

7. • Excess intake of alcohol leads to excessive
production of NADH, with a concomitancy
decrease in NAD+, produces metabolic
changes as follows:
1. Increased lactic acid production also can
result in hyperlactacidemia. The
hyperlactacidemia reduces the capacity of
the kidney to excrete uric acid, leading to
secondary hyperuricemia and causes
aggravation of gout.

8. • The increased availability of NADH favors the
reduction of pyruvate to lactate and oxaloacetate
to malate and decreasing its availability for
gluconeogensis and decreased synthesis of
glucose. This can lead to hypoglycemia.
• The increased ratio of NADH/NAD also inhibit
oxidation of fatty acids and citric acid cycle and
promotes lipogenesis and cholesterol synthesis
from acetyl-coA.
• Accumulation of lipid in most tissues results in
fatty liver, fatty renal tubules.
• The drug called disulfiram, going to inhibit the
activity of acetylaldehyde dehydrogenase