Regulation of Cholesterol Synthesis Flashcards
What is the major cholesterol regulatory mechanism?
regulation of HMG CoA reductase(HMGR)
The 4 main mechanisms of HMGR regulation
- Sterol-dependent regulation
- Sterol-independent regulation
- Hormonal regulation
- Medication(statins)
What do low levels of cholesterol cause w.r.t sterol-dependent regulation?
transcription factor, sterol regulatory element binding protein (SREBP) to be cleaved from the ER membrane
it travels to the nucleus and binds to the DNA at the sterol regulatory element(SRE) and this causes an upregulation of the production of HMGR
What do high levels of cholesterol do w.r.t to sterol-dependent regulation?
it prevents the cleavage of active SREBP
The major way of cholesterol biosynthesis regulation is ………………
sterol-dependent regulation
When is HMGR most active?
in its unmodified form
What happens when there are low ATP levels in the cell ?
leads to high AMP levels
What happens due to high AMP levels w.r.t sterol-independent regulation?
AMP activates certain protein kinases which in turn phosphorylate HMGR reducing its activity leading to a decrease in cholesterol synthesis
After eating, insulin is released. What does this do to HMGR expression?
causes the upregulation of HMGR expression
Which 2 hormones cause the down-regulation of HMGR expression?
glucagon and epinephrine
Which 2 hormones cause the down-regulation of HMGR expression?
glucagon and epinephrine
Why does release in insulin cause the upregulation of HMGR expression?
because after eating, the body needs to produce lipoproteins to help digest fats and cholesterol is a component of lipoproteins
What kind of inhibitors are statins to HMGR and why?
competitive inhibitors because they resemble HMGR
What disease are statins used to treat?
hyperlipidemia(high fat level)
How do statins play a role in cholesterol biosynthesis regulation?
they block cholesterol synthesis in the liver and induce cholesterol uptake from the blood (reverse cholesterol pathway)
