Lipoproteins & Cholesterol Homeostasis Flashcards
lipoproteins shuttle ____, ____ (so we don’t form plaques)
LDL levels are now determined by ____
TAG’s
cholesterol esters
ELISAs
Normal Levels
Glucose = ____
Total serum cholesterol = ____
Serum TAG = ____
Serum HDL = ____
< 100 mg/dL
200 mg/dL
150 mg/dL
> 40 mg/dL
Cholesterol and TAG Rich Lipoproteins
- Body balance of circulating lipoproteins.
- Relationship between intracellular cholesterol and circulating cholesterol levels.
- Role of LDL in formation of ____ and ____
- Role of HDL in ____ transport
fatty streaks
atheroscleoritc plaque
reverse cholesterol
Cholesterol and TAG Rich Lipoproteins
relationship bt plasma cholesterol and coronary heart disease mortality rates are NOT ____
as plasma cholesterol elvels increase, you see a ____ in mortality
linear
substantial rise
Consequences of elevated plasma cholesterol
elevated plasma cholesterol >
elevated ____ > fatty streaks (yellow steaks) > form the basis for the recruitment of additional ____ and proliferation of ____ > formation of a ____ (all that is remaining of the lumen of the endothelium)
LDL
cholesterol
smooth muscles
thrombis
Lipoproteins
Common Features Synthesized in the \_\_\_\_ or \_\_\_\_. Exchange \_\_\_\_ and \_\_\_\_ while in circulation. Nascent or immature vs. mature forms vs remnants
intestines
liver
lipids
proteins
Lipoproteins
three forms: nascent (immature) form, mature form, remnant form (as it loses ____)
largest = ____ (TAG rich; L/P ratio is very lipid rich) (from ____ TAG/cholesterol)
smallest = ____ (can take cholesterol into itself and remove from the ____)
VLDL = ____ synthesized TAG/cholesterol
lipid chylomicron dietary HDL plasma membrane de-novo
Apo-proteins
Role of Apo-proteins Increase \_\_\_\_ Maintain \_\_\_\_ May act as \_\_\_\_ May serve as ligands for \_\_\_\_
hydrophilicity
structure
enzyme activators
endocytosis
Apo-proteins
apo-proteins will determine ____ of individual lipoproteins
ApoA-1 > specific for ____
ApoB-48 > ____ (not the ligand for the ____ receptor)
ApoB-100 > ____ (ligand for the ____ receptor)
ApoC-2 > activates ____
ApoeE > involved with ____, involved with clearance > the ____ protein; allows the lipoproteins to be exited through the live
primary functions HDL chylomicron LDL VLDL LDL lipoprotein lipase all "exit"
The fate of a chylomicron
ApoE
• Chylomicrons- Carry ____ after re-esterification and packaging with ____.
dietary FA
apoB48
The fate of a chylomicron
in core: ____ and ____ (everything in core has FA); ____ is the outer monolayer
as passes through circulation; ApoC2 activates ____; TAG core of chylo is digest (FA used by ____ for energy; or into ____ and stored as TAG)
glycerol backbone > ____; used in syntehsis of phospholipds and TAGs
once TAG core depleted > becomes a ____ at this point; the ____ allows the remnant to bind to receptor on liver, be taken up and whatever is remaining will be broken down in ____ (free FA, cholesterol)
TAG
cholesterol ester
cholesterol
lipoprotein lipase
muscle
adipocytes
liver
remnant
ApoE
receptor-mediated endocytosis
Cholesterol and TAG Transport
• LDL is made from ____ through an ____ in the circulation
• ____ is the ligand for the LDL receptor.
• LDL has a long ____ and ____ concentration in plasma, hence it carries most ____ as cholesterol and Chol. Esters.
VLDL IDL ApoB100 residence time high plasma cholesterol
Cholesterol and TAG Transport
chylo - ____ FA
VLDL - ____ FA from liver; synthesized in the liver, contain an ____; which activate LPL > get a free FA that is used for energy in muscle or stored in adipocytes
VLDL > becomes an ____; half of the IDL is taken up by liver via ____; the other half is going to have that TAG-core cleaved even further > now becomes an ____ (the core is diminished even further; ____)
LDL: deliver choelsterol to ____ (40% to peripheral; 60% taken up by liver via ____)
LDL = ____ cholestroal; the longer it circulates (longer the residence time) > the more likely that the LDL will become ____; when it’s oxidized; it’s taken up by ____ (which makes ____) and stimulates ____ [this is the absolute worst type of lipoprotein]
dietary
newly synthesized
ApoC2
IDL
ApoE
LDL
hepatic TAG lipase
peripheral tissues
ApoB100
bad oxidized macrophages foam cells artherosclerotic plaque formation
High Density Lipoproteins (HDL)
HDL- synthesized in ____; little bit in ____
Transfers Apo E and Apo CII to ____ and ____
Exchanges cholesterol esters for TAG of ____ in a reaction catalyzed by ____
liver gut chlyomicrons VLDL VLDL CTEP (cholesterol ester transfer protein)
High Density Lipoproteins (HDL)
Why is CETP beneficial?
• Catalyzes the transfer of ____ to VLDL which can now become a ____ (via lipoprotein lipase) which is taken up by the liver, hydrolyzed, and converted to ____.
allows HDL to pick up more ____ (and reverse chol trasnport)
decreasing TAG rich of core of VLDL; TAG-rich core is now depelted and can return to ____
(CETP and LPL have ____)
cholesterol esters
VLDL remnant
bile acids
cholesterol
IDL
similar functions
High Density Lipoproteins (HDL)- exchange of apo-proteins
HDL deliver ____ and ____ to nascent chylomicrons and nascent VLDL
After apo-CII activates Lipoprotein Lipase- it is ____ from the mature chylomicron
or the mature VLDL and returns back to ____
HDL in BS > flat structure > lipid ____ structures
give Apo-C2 and ApoE to chylomicrons or to nascent VLDL’s (once it is within, it is now ____)
ApoCII ApoE removed HDL poor activated
Role of HDL-Reverse Cholesterol Transport
 HDL picks up cholesterol from the ____ and converts it to cholesterol esters with ____.
LCAT is activated by ____.
The cholesterol esters are delivered back to the ____ were they are utilized in bile acid formation or repackaged
____, scavenger receptor on liver binds HDL
cell surface LCAT ApoA1 liver SRB1
Role of HDL-Reverse Cholesterol Transport
HDL can now take up cholesterol from the outer monolayer from msot cells; once it takes up cholesterol > it must ____ it (bc it esterifies within the core) > now a chol ester (using LCAT)
circulating HDL can go to liver > through a scavenger receptor (SRB1) > aren’t ____, the HDL can dump the lipid into the liver (SRB1 high ____ little ____)
esterify
endocytosed
capacity
specificity
Regulation of Inter and Intra cellular cholesterol
Intracellular cholesterol levels through a balance between ____ and ____ of LDL particles by the LDL receptor.
intracellular cholesterol regualtes ____ cholesterol (the ones associated with LDL’S); this balance leads to an increased ____ of the LDL (of intracellular cholesterol and circulating LDL’s)
LDL-____ (mecahnism in peripheral cells)
cholesterol synthesis
receptor mediated endocytosis
extracellular
residence time
receptor-mediated endocytosis
Relationship Between Serum and Intracellular Cholesterol Levels
1. Regulation of cholesterol biosynthesis. A. At level of \_\_\_\_ \_\_\_\_ dependent \_\_\_\_ expression Degradation of HMGCoA reductase by \_\_\_\_
- Regulation of LDL receptor number.
At level of ____ as cholesterol levels increase ____ of LDL receptor expression.
inside the cell: ____
regulated by number of LDLR’s on the cell surace (____ of the cell; regulates how much is taken up)
HMGCoA Reductase
hormone
gene
proteolysis
gene expression
down-regulate
HMG CoA Reductase
outside
Regulation of Inter and Intra cellular cholesterol
1. When cells require cholesterol take up ____ via LDL-receptor
- LDL-Receptor complex is ____- and intracellular cholesterol increases
- Cholesterol is stored as a ____ (via ACAT).
- Increase intracellular cholesterol inhibits
– ____ and down regulates ____ either via recycling or at level of synthesis. Will also decrease ____ levels - As cholesterol levels inside cell decrease, cholesterol synthesis is ____ and LDL-receptor expression and cells surface localization ____
LDL endocytosed cholesterol ester cholesterol biosynthesis LDL-receptor on cell surface HMG CoA Reductase stimulated increases
Esterification of intracellular cholesterol
The fatty acyl chain that is attached to the cholesterol is often ____
or ____
palmitate
oleate
When you just have bad genes…
familial hyperalphlipoporteinemia > increases your ____ > ____, longer life
____ classes of mutations of LDL receptor
LDL receptor has a ligand binding domain; EGF precursor homology (maintains ____); cytoplasmic domain (helps in ____)
mutations in any one of these regions > various levels of ____ (depending on whether you’re homo/hetero for that mutation)
genetic predispositions to ____ circulating LDL’s
HDL beneficial 4 structure RM endocytosis
hypercholesteroemia
increased
Familial hypercholesterolemia: half the normal amount of LDL receptor isn’t enough!
- ____ inherited disease due to mutations in LDL receptor gene
- ____ have elevated cholesterol and early onset of cardiovascular disease (age 30-40)
- ____ have very high cholesterol and often suffer heart attacks in childhood
dominantly
heterozygotes
homozygotes
