Question

Briefly describe the regulation of cholesterol synthesis via short term (hormonal) controls

Answer 1

The principal site of cholesterol biosynthesis is liver.The amount of cholesterol that is synthesized in the liver is regulated by dietary cholesterol levels.When dietary intake of cholesterol is high synthesis is decreased and when dietary intake is low synthesis is increased.The other sites of cholesterol synthesis are adrenal cortex,skin,gonads and intestine.Enzymes of cholesterol synthesis are situated in microsomes and cytosol.Regulation of cholesterol synthesis is controlled by HMG-CoA reductase.HMG-CoA reductase is regulated by phosphorylation and dephosphorylation also.

Cholesterol is synthesized from acetyl CoA.Synthesize occurs in 5 steps.

1-Synthesis of HMG CoA.Two molecules of acetyl CoA condense to form acetoacetyl CoA.This condense with one more acetyl CoA to form HMG CoA.HMG CoA is present both in mitochondria and cytosol.

2-Formation of mevalonate.HMG CoA reductase is a rate limiting enzyme.HMG CoA is reduced to mevalonate,reducing equivalents are supplied by NADPH (Nicotinamide adenine dinucleotide phosphate).

3-Production of isoprenoid units.Mevalonate is phosphorylated by ATP and decarboxylated to form isoprenoid units.

4-Synthesis of squalene.6 isoprenoid side units condense to form squalene.NADPH is also required.Cyclization of squalene forms lanosterol.This requires NADPH and molecular O2.

5-Conversion of squalene to cholesterol.Conversion of lanosterol to cholesterol takes place by removal of extramethyl groups and shift of double bond.

The phosphorylation of HMG-CoA reductase which is triggered by glucogon through AMPK decreases the activity of enzyme ,while dephosphorylation is induced by insulin through PP2A.

This is the brief discription of regulation of cholesterol biosynthesis.