Cholesterol Regulation
Cholesterol Synthesis
Cholesterol Regulation
- 1)HMG-CoA Reductase
- Choesterol feedback inhibits
- Genetic regulation – reductase mRNA
- Cholesterol LOW
- SCAP facilitates proteolytic cleavage of SREBP
- SREBP goes to the cytoplasm
- SREBP goes to nucleus
- SREBP + SRE – INC transcription
- Cholesterol HIGH
- SCAP does not facilitate the cleavage of SREBP
- SREBP in nucleus is degraded
- 2)Rate of Translation
- INH Mevalonate derived intermediates – step 3,4,5a products
- INH dietary cholesterol
- 3)Rate of HMG-CoA Reductase degradation
- Membrane domain changes conformation to enable proteolysis
- 4)Phosphorylation
- INH AMP activated protein kinase
Terminology:
- Sterol regulatory element binding protein (SREBP)
- (SREBP) transcription factor binds to the DNA sequence SRE
- Normally bound to ER
- Sterol Regulatory Element (SRE): transcription factor
- Gene that encodes the MMG-CoA reductase
- SREBP-Cleavage Activating Protein (SCAP)
