Question

Significance of the rate limiting step of cholesterol biosynthesis

Answer 1

Explanation:

Cholesterol levels in the body come from two sources, dietary intake and biosynthesis. The majority of cholesterol utilized by healthy adults is synthesized in the liver, which produces ~70% of the total daily cholesterol requirement (~1 gram). The other 30% comes from dietary intake.

Biosynthesis of cholesterol generally takes place in the endoplasmic reticulum of hepatic cells and begins with acetyl- CoA, which is mainly derived from an oxidation reaction in the mitochondria. However, acetyl-CoA can also be derived from the cytoplasmic oxidation of ethanol by acetyl-CoA synthetase. Acetyl-CoA and acetoacetyl-CoA are converted to 3-hydroxy- 3-methylglutaryl

Answer 2

Explanation:

Acetoacetyl-CoA condenses with another Acetyl-CoA molecule to form 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA). HMG-CoA is reduced to mevalonate by NADPH. This is the rate limiting step in cholesterol synthesis, which is why this enzyme is a good target for pharmaceuticals (statins).