Biochemistry Flashcards
Where does the body derive most of its cholesterol and fatty acids?
Primarily the Liver, and secondarily the diet
How would you arrange the following fatty acids in a lipoprotein and why?
TAG, Cholesterolesters, Leithin, cholesterol
According to hydrophobicity: From center outward I would have- cholesterolester, TAG, cholesterol, and Leithin
Why is lipoprotein lipase located on endothelial cells; why not in the lipoproteins themselves?
It’s tethered to them so it can “catch” lipoproteins in the blood and then break them up so they can diffuse into the endothelial cells. If they were in the lipoproteins they would end up breaking the fats apart and they would prematurly diffuse out of the lipoprotein.
By what mechanism and by what molecules are TAG and cholesterolesters broken down in the small intestine?
oxidation
cholesterolesterase and pancreatic lipase
How do apo proteins facilitate fatty acid and cholesterol transport? Which proteins are on chylomicrons, VLDLs and HDLs?
They provide a surface upon which these hydrophobic molecules can aggregate
chylomicrons B48 (subset B100)
VLDL B100
HDL A1
Whats so special about acyl-CoA in fatty acid synthesis? How is it formed?
Acyl-CoA is an activated fatty acid and facilitates the formation of cholesterolesters, and TAG. Both cholesterol and glycerol attack the high energy sulfur bond of the activated fatty acid acyl-CoA; to form their product and recycle Coenzyme A in the process.
Its formed when ATP and a fatty acid come together (releasing pyrophosphate), and are then attacked by a high energy sulfur bond from Coenzyme A. The Coenzyme A then becomes acyl-CoA because of the addition of this fat.
What’s the name of the enzyme that facilitates cholesterol becoming cholesterolester (by attacking acyl-CoA)?
Acyl-CoA cholesterol transferase.
Explain L-CAT and P-CAT.
Lecithin and phosphatidycholine are the same molecule they both help to transfer an activated fatty acid to cholesterol to make a cholesterol ester, and are found in HDL among other places.
Lecithin-cholesterol acyl transferase
Phosphatidycholine acyl transferase
Where are B48, 100, and A1 expressed?
B48 intestines and marks lipoproteins containing mostly dietary lipids-chylomicrons (produced in enterocytes)
B100 in the liver and marks lipoproteins containing mostly endogenous (de novo) lipids-VLDL (liver)
A1 both the intestines and liver marks HDL and reverse cholesterol transport
What role does cholesterolester transfer protein play in lipid metabolism?
It transfers cholesterolester from HDL to VLDL, and TAG from VLDL to HDL.
This is the reason for the inverse relationship between TAG and HDL. Increasing TAG will increase VLDL and more of these will bump into HDL and steal its cholesterolester until the levels of HDL decrease and are eliminated by the kidney.
How does the experimental drug torcetrapib work?
Inhibits CETP increasing HDL-C (cholesterol) levels
What’s the name of the rate limiting molecule in cholesterol synthesis?
Mevalonic acid
If you decided a cholesterol lowering drug to block isoprenoids would you have to worry about myalgias?
Yes isoprenoids make polyprenoids which make ubiquinone (ETC). If ubiquinone is decreased energy metabolism will decrease affecting muscle.