Choolesterol Synthesis

The first cholesterol promoter is the dietary cholesterol. When intracellular cholesterol concentration decreases the (sterol regulatory element-binding proteins)SREBP and (SREBP cleavage-activating protein)SCAP is escorted to the Golgi complex .There, two proteolytic cleavages of SREBP release a regulatory fragment which enters the nucleus and activates transcription of its target genes, including HMG-CoA reductase ,LDL receptor protein and a number of other proteins needed for lipid synthesis.(3)
The second promoter of cholesterol synthesis is the hormone insulin. Insulin promotes dephosphorylation (activation of HMG-CoA reductase) which promotes cholesterol synthesis in which insulin binds to its receptor protein in the liver cell membrane and stimulate irs-1 formation.irs-1 activates HMG-CoA reductase enzyme increasing rate of cholesterol synthesis.(4)

FACTORS
When intracellular cholesterol level increases, the proteolytic of SREBP (sterol regulatory element-binding proteins) is blocked and the SREBP in the nucleus is rapidly degraded which suppresses the expression of the HMG-CoA reductase gene along with 20 other genes involved in its biosynthesis and uptake including the gene encoding the LDL receptors. This is called feedback mechanism. (3)

Lastly, is the hormonal regulation of cholesterol synthesis.In hormonal regulation of cholesterol synthesis glucagon binds to receptors in liver cell membrane and stimulate cAMP formation.cAmp activates protein kinase which inactivates the rate limiting HMG-CoA reductase enzyme thus decreasing cholesterol