Cholesterol Biosynthesis Flashcards
Cholesterol has a crucial role in the structure of ____
Membranes
What is cholesterol a precursor for?
Steroid hormones and bile salts
Why is cholesterol not required in the diet?
Because all cells can synthesize cholesterol from simple precursors
What is Smith-Lemli Opitz Syndrome?
Syndrome with multiple malformations and mental disability associated with defective cholesterol biosynthesis due to defective enzyme in final step of cholesterol synthesis pathway
Although all cells can synthesize cholesterol, where is it primarily made?
The liver
What is the fate of cholesterol produced by the liver?
Small amount incorporated into hepatocyte membranes, most exported
What compound is cholesterol made of?
Acetyl coA (4)
What is the rate limiting step of cholesterol synthesis?
reduction of HMG-CoA to mevalonate by HMG-CoA reductase
What enzymes do statins inhibit?
HMG-CoA Reductase
How is HMG-CoA reductase regualted at the level of the enzyme?
- Cholesterol inhibits the enzyme allosterically via feedback inhibition
- Cholesterol and cholesterol derivatives promote rapid degradation of the enzyme via ubiquitin/proteasome
How is HMG-CoA reductase regulated at the level of the genome?
- Cholesterol can inhibits its own transcription in the nucleus
Describe the hormonal regulation of HMG-CoA reductsae.
- The enzyme is inhibited when it is phosphorylated.
- Glucagon –> stimultes kinase –> phosphorylates HMG-CoA reductase –> inhibited
- Insulin –> stimulates phosphatase –> removes phosphate –> HMG-CoA reductsae active
What enzyme is responsible for esterifying cholesterol?
Acyl-CoA-Cholesterol Acyl Transferase (ACAT)
What happens to newly formed cholesterol in the liver?
It is esterified and packed into VLDL
What is the purpose of esterifying cholesterol?
Makes it less polar so it is able to enter lipid droplet