Cholesterol Biosynthesis

Citrate transport system moves acetyl CoA from mitochondria into cytoplasm. Thiolase, HMG CoA synthase, and HMG CoA reductase (rate-limiting) convert it into mevalonate. Mevalonate is then converted into IPP and then cholesterol.

Cholesterol can be esterified and stored in the cell via ACAT, or it can be secreted as a lipoprotein and then converted via LCAT.

Transcriptional Control
If there is a high level of cholesterol, it binds to SCAP and inactivates it. If there is low cholesterol, then SCAP is active. SCAP-SREBP can be transported into the Golgi, where the proteases cleave off the DNA binding domain. That DNA binding domain goes into the nucleus and interacts with SRE. SREBP can then activate the genes for HMG CoA reductase synthesis.

Post-transcriptional control includes proteolysis of the reductase or degradation of the HMG CoA reductase mRNA.

Phosphorylation
Glucagon --> phosphorylation of HMG CoA reductase via kinase like AMPK --> decrease cholesterol synthesis
Insulin --> dephosphorylation of HMG CoA reductase via phosphatase --> increase cholesterol synthesis