The regulatory enzyme in the biosynthetic pathway of cholesterol is
|A||Hydroxymethylglutaryl Co. A synthetase|
|B||Hydroxy methyl glutaryl Co-A reductase|
Cholesterol synthesis: -
a. Cholesterol is derived about equally from diet and Biosynthesis 50%
b. Synthesis: - 500mg/day, 10% of total in Liver, 15% in gut and rest are in skin. The microsomal
c. endoplasmic reticulum and cytosol fraction of the cell is responsible for synthesis.
d. Acetyl-CoA is the source of all ‘C’-atoms in cholesterol
e. Synthesis in 5-stages
[I] 1st →Acetyl CoA Forms HMG-CoA and Mevalonate:
* HMG —CoA reductase
a. is a microsomal enzyme, rate limiting step in the pathway of cholesterol synthesis
b. it activity is decreased by fasting, LDL cholesterol, Mevastatin, Lovastatin, Mevalonate.
c. Insulin and thyroid hormones increase its activity.
d. Glycogen and glucocorticoids decrease its activity
e. The Enzyme is in active form when dephosphorylated and in inactive form when phosphorylated.
[II] 2nd→Mevalonate forms active Isoprenoid units: - By means of a decarboxylation, the active isoprenoid units, Isopentenyldiphosphate, is formed
[III] 3rd→ Six — Isoprenoid units form squalene
[IV] 4th→Squalene is converted into Lanosterol
[V] 5th→Lanosterol is converted into cholesterol
** Farnesylpyrophosphate, that gives rise to squalene, also gives rises other imp. isoprenoidseg. Dolichol, Ubiquinone.