Question

describe the mechanisms controlling cholesterol synthesis.

Answer 1

Mechanisms Controlling cholesterol synthesis:

Regulation of HMGR activity is the primary means for Controlling the level of cholesterol synthesis. The four distinct mechanisms control the cholesterol synthesis. They are

1. Feed back inhibition

2. Competitive inhibition

3. Covalent modification (Role of hormones)

4. Sterol mediated regulation of transcription

1.Feed back inhibition:

*HMG Co A reductase is inhibited by Mevalonate and cholesterol. (HMG Co A reductase (3- hydroxy-3-methyl-glutaryl-coenzyme A reductase) which is termed as HMGR.

* Mevalonate is immediate product of HMG Co A reductase which is catalyzed reaction. When comes to cholesterol it is the best product of reaction pathway.

2. Competitive inhibition:

Statins are the reversible competitive inhibitors of HMG Co A reductase which are used to decrease plasma cholesterol levels in the patients of hypercholesterolemia(presence of high levels of cholesterol in blood).

Example for statins are lovastatin, mevastatin etc.,

3. Covalent modification:

The activity of reductase is decreases by Phosphorylation.

Glucagon( it is the peptide hormone produced by alpha cells of pancreas. It works to raise the concentration of glucose and fat in blood stream).

Glucagon favours the inactive which is in Phosphorylation form formation which helps in decreasing the rate of cholesterol synthesis.

Cholesterol synthesis ceases when the level of ATP is low.

The dephosphorylated form of HMG Co A reductase increase the rate of cholesterol synthesis which is favoured by insulin.

4. Sterol mediated regulation of transcription:

The synthesis of cholesterol is also regulated by amount of cholesterol taken up by cells during lipoprotein metabolism.

The rate of synthesis of reductase mRNA is controlled by this method.

Chylomicrons remnants by liver cells which is internalized and peripheral tissue which provides cholesterol which helps in decrease in the transcription of HMG Co A reductase Gene, which leads to decrease in conrollCont of cholesterol synthesis.