Week 3 - Cholesterol Metabolism - Skildum Flashcards
What are the 4 stages of cholesterol synthesis?
- Three acetyl CoAs make mevalonate (six carbons)
(rate-limiting step, important) - Mevalonate converted to isoprenes (5 carbons)
- Six isoprenes condense to form squalene (30 carbons)
- Squalene is cyclized and converted to cholesterol (27 carbons)
Where is the main source of cholesterol synthesis?
What are the 2 ways it can be exported?
The Liver!
Cholesterol esters or bile acids
What is the rate-limiting step in bile acid synthesis?
How is it regulated?
The hydroxylation of cholesterol to t-alpha-hydroxycholesterol.
Bile acids inhibit this enzyme
How are bile acid conjugates made? What is the advantage of their creation?
The side chains of bile acids bind to taurine or glycine to form bile acid conjugates.
Conjugates are better detergents than normal bile salts.
How much cholesterol is lost from the body and how?
During recycling about 5% is lost out the feces, the other 95% is sent back t the liver to be reprocessed
What happens to TAGs between getting incorporated into bile salts and getting into the blood stream?
- Lipase slices off two fatty acids to make monoacylglycerol and two free FAs.
- The FA’s and MAGs enter the endothelial cell
- They are recombined into TAGs
- The TAGs enter chylomicrons
- Chylomicrons enter the lymph and then blood
What is the main job of HDL?
- To maintain the homeostasis of other particles.
- Transfers cholesterol esters, proteins, triglycerides and phospholipids among lipoproteins and cells
What does HDL do facilitate the creation of mature chyomicrons?
HDL transfers ApoC to nascent chylomicrons. ApoC activates lipoprotein lipase (LPL)
What does HDL do facilitate the creation of mature chyomicrons VLDL?
HDL transfers ApoC and ApoE to nascent VLDL. ApoC activates lipoprotein lipase (LPL)
What is the function of the LDL receptor? How can disease stem from problems with it?
The LDL receptor is the receptor on peripheral cells, they use it to bring in LDL to get cholesterol, AAs, FAs, glycerol etc…
When its not working, there will be A LOT of cholesterol hanging around in the blood stream. Macrophages will be taking it out of the blood stream. But when they get overwhelmed the can turn into foam cells. Foam cells can build up and form plaques. They can get nasty and clog stuff up.
Explain congenital adrenal hyperplasia:
Problems with Cyp21 (One of the steroid hormone biosynthesis genes)
These patients have low cortisol and aldosterone and high androgens
This increase of androgens causes females with the problem to be masculinized.
Where do steroid hormones like cortisol bind to influence a cell?
They diffuse through the membrane and bind to ligand-binding domains on the steroid receptor. The receptor can then bind to DNA and recruit transcription factors and polymerase.
What is Vitamin D’s function and how is it formed?
Requires reactions in the skin (UV), liver and then kidney.
