L22 Cholesterol Flashcards
Hyper-chylomicronemia can be caused by… (select all that apply)
A. apoA-I deficiency
B. ApoE deficiency
C. Lipoprotein lipase deficiency
D. ABCA1 mutations
E. ApoC-III mutations
C, E since they would result in NO chylomicron breakdown
B would result in increased chylomicron remnants since they will not be taken up by the liver
A, D concern HDL, not chylomicrons
Abnormally high [LDL] in plasma can be caused by loss of function of… (select all that apply)
A. Lipoprotein lipase
B. LDL-R
C. ApoB-100
D. Pancreatic lipase
E. ABCA1
B, C since without either LDL-R or ApoB-100, LDL cannot be taken up by the liver or peripheral tissues
E is related to HCL not LDL
D is in the GIT so there’s no effect
A is related to chylomicrons
Low HDL concentrations may result from mutations in… (select all that apply)
A. LDL-R
B. lipoprotein lipase
C. LCAT
D. ABCA1
E. apoA-I
C, D, E: LCAT is needed for HDL maturation (pre-HDL -> HDL), ABCA1 and apoA-I are needed for HDL precursor (pre-HDL)
What does ABCA1 do?
It is a floppase that transport cholesterol from the inner leaflet to the outer leaflet so that it can interact with apoA-I (and pre-HDL)
What does LCAT do?
It turns pre-HDL into HDL (maturation)
What does CETP do?
It transports cholesterol ( cholesteryl ester) from HDL into VLDL and TAG from VLDL into HDL
What happens if SRB1 is non-functional?
HDL cargo cannot be transferred to the liver
What happens if you have LDLR-deficiency?
Too much LDL -> high CVD risk
What happens if you have ABCA-1 deficiency?
Too little HDL -> high CVD risk
What is good and bad cholesterol?
There is no good or bad cholesterol: too much LDL or too little HDL both cause high CVD risk
HDL vs LDL: what do they do?
HDL removes excess cholesterol
LDL carries cholesterol to cells
Where does NADPH come from?
PPP cycle
TF: cholesterol synthesis requires NADH
F, it requires NADPH
TF: cholesterol can be synthesized by isoprenoids
True
What is the key regulatory enzyme in cholesterol synthesis and what does it produce?
HMG-CoA reductase, mevalonate
TF: cholesterol can be synthesized from acetyl-CoA
True
How much ATP and NADPH is required for the synthesis of 1 cholesterol molecule in the mevalonate pathway
36 ATP and 16 NADPH
What is farnesyl pyrophosphate?
It is a cholesterol precursor (right before squalene) that acts as a lipid anchor meaning it anchors the protein to the membrane (non-raft)
What are the 2 ways cholesterol is regulated through homeostasis?
Body: diet + synthesis vs excretion
Cell: uptake from circulation vs efflux from cell
LDLR vs ABCA1: which one is involved in uptake of cholesterol and which one is involved in efflux of cholesterol?
LDLR = uptake: cholesterol from LDL is absorbed into cell
ABCA1 = efflux: cholesterol is transformed into preHDL (then to HDL)
What is cholesterol excreted as?
Build acids and biliary cholesterol
What are the 2 ways to regulate cholesterol synthesis via HMG-CoA reductase?
- Energy state
- Gene regulation ‘ sensing [cholesterol]
What is the melavonate pathway
It is the pathway for cholesterol and other isoprenoid synthesis (aka HMG-CoA reductase pathway or isoprenoid pathway)
In what state is HMG-CoA reductase in when high [AMG]/[ATP]
High [amg/atp] describes a low energy state. The lack of atp means cholesterol synthesis cannot occur so hmg-coa reductase is off/inactive and phosphorylated
