Biochemistry - Fatty Acid Transport and Catabolism Flashcards
In which organs are HDL synthesized?
Liver and intestine - released as a “nascent HDL disc”
Which apoprotein is present on VLDL?
B100
What is the composition of TAGs vs. CEs in VLDL?
TAGs»_space; CEs
What does HDL transfer to VLDL upon entering the bloodstream?
Apo CII and E
What receptor does VLDL bind to on cells that need FFAs?
LPL
When a VLDL transitions to become an IDL, what two things happen?
- TAGs = CEs
2. Loss of Apo CII
After VLDL becomes an IDL, what two things can happen to it in a liver cell?
- If body cells have enough FAs, IDL will bind to LDL-R, get entocytosed, and reused for synthesis or more VLDLs.
- Bind to hepatocyte TAG lipase (HTGL) receptor, TAGs go into liver cell for hydrolysis, IDL loses Apo-E and becomes a LDL.
What is the defect in people with familial hypercholesterolemia?
Defective or too few LDL-receptors - unable to take in cholesterol from LDL. LDL gets oxidized, invades blood vessel endothelium.
What macrophage receptors bind oxidized LDL in the intima of blood vessels? What does this result in?
Scavenger receptors bind, macrophage eats LDL, which eventually results in a foam cell. Foam cells stimulate metalloproteases for angiogenesis and they also release growth factors and cytokines.
What HDL apoprotein activates lecitin cholesterol acyl transferase (LCAT)?
Apo A-I
What does LCAT do?
Allows HDL to take cholesterol from cells that have too much:
Transfers a FA from lecithin to the excess cholesterol to make a cholesterol ester, which is then transferred to HDL, which travels back to the liver for endocytosis and degradation.
Which enzyme is used to transfer CEs from HDL to IDL and TAGs from IDL to HDL? Why is this done?
Cholesterol ester transfer protein. It generates LDL that can deliver cholesterol to cells that need it.
What is the half life of VLDL?
~3 hours
What is considered a normal cholesterol level?
~200 mg/dl
What are normal HDL and LDL cholesterol levels?
HDL: 40 mg/dl, LDL: 120 mg/dl
What are the relative sizes of chylomicrons, VLDL, LDL, and HDL?
Chylomicrons > VLDL > LDL > HDL
What are the relative densities of chylomicrons, VLDL, LDL, IDL and HDL?
HDL > LDL> IDL > VLDL > Chylomicrons
20% of previous cases of sudden infant death syndrome (SIDS) is thought to have been due to a deficiency of what enzymes involved in FA metabolism?
The FA coA dehydrogenases (VLCAD, LCAD, MCAD, and SCAD)
How does glucagon affect TAG catabolism in apipose cells?
Glucagon (and epi) phosphorylate protein kinase A, which activates TAG lipase (aka hormone sensitive lipase), which breaks TAGs into FFAs.
What problem does the carnitine cycle solve?
It gets fatty acids into the mitochondrial matrix so they can be used in ATP synthesis.
What do unsaturated FAs require for catabolism? Is as much energy gained as a saturated FA?
They require two extra steps by a reductase and an isomerase. This skips out on gaining FADH2 so two fewer ATP are made from them.
What is Refsum’s disease?
Inability to do alpha-oxidation.
Why is alpha-oxidation done?
It is done for branched FAs because beta-oxidation is not possible if the beta carbon has branching.
What enzymes are involved in the carnitine cycle?
- CATI combines FA-coA and carnitine to generate coA and FA-carnitine. FA-carnitine enters the mitochondrial matrix.
- CATII (in the matrix) regenerates FA-coA and unbound carnitine. Carnitine exits the matrix to be re-used in the cycle.
