Biochemistry 6: Lipid Metabolism Flashcards
What is the point of having lipoprotein particles? Why don’t amino acids, or sugars, have their own special transport particles, as well?
Need amphopathic (polar and non polar ends) molecules to allow for transport of nonpolar lipids. Both amino acids and sugars are polar, so themselves would dissolve in the water-containing blood/serum.
What does a lipase do? What is the purpose?
Cleaves triacylglycerol (TAG) to release free fatty acids
Free fatty acids can cross cell membranes, and are what the cells actually use as fuel (TAGs canNOT cross cell membranes)
What would happen if I wanted to get a TAG from my diet to my muscle for oxidation? Where in the muscle would oxidation take place/how would it get there?
TAG packages into chylomicrons → circulate to peripheral tissue → lipoprotein lipase on endothelial surface of muscle cell cleaves TAGs into free fatty acids (FFAs) → FFAs cross cell membrane → within muscle, transported via carnitine shuttle (inhibited by malate, right??) → within mitochondria, oxidation occurs, where acetyl-CoA that comes from the FFA oxidation can feed directly into the TCA cycle
Apo B-48 – use its function to explain what lipoprotein particles it is found on
Mediates chylomicron secretion; found on chylomicrons + chylomicron remnants
Logical, since it would start out on chylomicrons since it is necessary for the chylomicron to form in the first place. Then, it would simply remain on the remnant as the TAGs are cleaved by LPL (lipoprotein lipase)
Apo E – use its function to explain what lipoprotein particles it is found on
Mediates remnant uptake; found on everything but LDL
Logical, since to make it ONTO remnants (IDL, chylomicron remnants), it would have to be on the remnant precursors (VLDL/chylomicrons)
Apo E – what lipoprotein particle is it NOT found on? Why would this make sense?
Not found on LDL
Logical, since LDL has its own receptor (B-100)
Apo E – what lipoprotein particle is it NOT found on? Why would this make sense?
Not found on LDL
Logical, since LDL has its own receptor (B-100)
Apo C-II – use its function to explain what lipoprotein particles it is found on
Activates lipoprotein lipase (LPL); found on chylomicrons + VLDL
Logical, since chylomicrons and VLDL have the highest proportion of triglycerides (TAGs). As such, they would need something on them to activate the LPL of tissues so that they can distribute those fatty acids/TAGs to the peripheral tissues.
Apo A-I – use its function to explain what lipoprotein particles it is found on
Activates lecithin-cholesterol acyltransferase (LCAT); found on HDL, chylomicrons
LCAT esterifies cholesterol, making cholesterol even more non polar. If the cholesterol is esterified → dissolve even better in the non polar inside of the lipoprotein particle → cholesterol storage capacity ↑
Logical that it would be in HDL in particular, since HDL’s role is to scavenge cholesterol from the periphery, so the more capacity the better!
Type I hyperlipidemia – use deficiency to explain what lipids would be elevated
LPL or C-II deficiency → chylomicrons ↑
Logical, since LPL (and C-II, which activates it) degrade triglycerides. Chylomicrons have a large proportion of triglycerides (although honestly I’m not sure why VLDL wouldn’t similarly be elevated…).
Type IIa hyperlipidemia – use deficiency to explain what lipids would be elevated
LDL receptor deficiency → LDL ↑
Type I vs. IIa hyperlipidemia – which gives you pancreatitis? Which gives you atherosclerosis? Why?
Type I – pancreatitis, but no atherosclerosis
Type IIa – atherosclerosis, but no pancreatitis
Pancreatitis: thought to be due to degradation of TAGs by pancreatic lipase → release of free fatty acids within pancreas → inflammation
Atherosclerosis: remember, atherosclerosis is thought to be driven by the “Bad cholesterol” LDL – only IIa has substantially elevated LDL
Type IV hyperlipidemia – use most common cause to explain what lipids would be elevated
Most common cause = overproduction of VLDL (e.g. alcoholism)
Recall from Biochem Mini Lecture #3: EtOH degraded to acetate, with overproduction of NADH. Acetate → acetyl-CoA → fatty acid synthesis ↑; NADH ↑ → glycerol-3-phosphate ↑. Free fatty acids + glycerol-3-phosphate → triglycerides ↑ → VLDL ↑ (logical that it would be VLDL and not chylomicrons, since VLDL contains TAGs synthesized by the liver, whereas chylomicrons are for dietary TAGs)
Abetalipoproteinemia – use defect to explain what you would see on intestinal biopsy. What kind of diarrhea would they have?
Defect in making chylomicrons + VLDL → inability to export lipid as chylomicrons → back-up/accumulation of lipid within enterocytes → malabsorption → steatorrhea
