Cholesterol II Synthesis II Regulation II Fate

STEPS OF CHOLESTEROL SYNTHESIS
1. Synthesis of HMG CoA
2. Formation of mevalonate
3. Conversion of mevalonate to activated isoprene units
4. Polymerization of six isoprene units to form squalene
5. Cyclization of squalene to form parent steroid nucleus lanosterol and
6. Formation of cholesterol from lanosterol

Regulation of cholesterol synthesis:
Competitive inhibition
Statins (Lovastatin, Mevastatin, Atorvastatin, etc.) are the reversible competitive inhibitors of HMG Co A reductase.
They are used to decrease plasma cholesterol levels in patients with hypercholesterolemia.
Feedback inhibition
HMG Co-A reductase is inhibited by Mevalonate and Cholesterol.
Mevalonate is the immediate product of HMG Co-A reductase catalyzed reaction whereas Cholesterol is the ultimate product of the reaction pathway.
Covalent modification (Role of hormones)
Phosphorylation decreases the activity of the reductase.
Glucagon favors the formation of the inactive (phosphorylated form) form, hence decreases the rate of cholesterol synthesis
In contrast, insulin favors the formation of the active(dephosphorylated) form of HMG Co A reductase and results in an increase in the rate of cholesterol synthesis
Cholesterol synthesis ceases when the ATP level is low
Fate :
Bile acids & Bile salts
Vitamin D3
Steroid hormones