Lipoproteins

Question 1

What do the lipoprotein complexes include? What happens when lipid deposition occurs?

Answer 1

Chylomicrons, VLDLs, intermediate density lipoproteins, HDLs; plaque formation and narrowing of blood vessels, or atherosclerosis

Question 2

What do lipoproteins contain? What is in the inside vs. the outside?

Answer 2

Have an: 1. inner hydrophobic core with TAGs and cholesterol esters and 2. outer shell with amphipathic phospholipids and FA chains facing innter core and polar head groups facing outside; unesterified cholesterol, and apolipoproteins

Question 3

How do you obtain TAG and cholesterol carried by lipoproteins?

Answer 3

Obtain them from the diet or de novo (exogenous vs. endogenous)

Question 4

What is the relationship of large chylomicrons and the smallest HDLs relative to size and density? What are two techniques to separate lipoprotein particles?

Answer 4

Chylomicrons are largest, then VLDL, then LDL, then HDLs, and with smaller size means greater density (protein:lipid ratio); use electrophoretic mobility or based on density (ultracentrifugation)

Question 5

What are some apolipoprotein functions? How would you divide apolipoproteins?

Answer 5

1. recgonition sites for cell surface receptors 2. activators for enzymes involved in lipoprotein metabolism 3. required structural components of the lipoprotein; classes (letters) and subclasses (Roman numerals)

Question 6

What is the most abundant apo-LP in HDL? What synthesizes it? what are a couple functions? What is it a ligand for?

Answer 6

Apo A-1; made in the liver and intestine; it activates LCAT and it is involved in reverse cholesterol transfer; ABCA1 and SR-B1

Question 7

Which apo-LP is associated with HDL and made in the liver?

Answer 7

Apo A-II

Question 8

Which apo-LP deals with VLDL assembly? What other function does this have?

Answer 8

Apo B-100; it is made in the liver, and is also involved in LDLR binding

Question 9

Which is the only apo-LP made in the intestine? What is it relative to Apo B-100? What is it key in the formation of?

Answer 9

Apo B-48, and it is 48% of apoB100; Chylomicron formation and secretion

Question 10

What do each of the ApoC apo-LPs do? Where are they made?

Answer 10

Each of the ApoC’s interferes with recognition of apoE by LP receptors or they displace apoE from lipoproteins; ApoC-I activates LCAT, ApoC-II activates LPL, ApoC-III inhibits LPL; made in the liver

Question 11

What is recognized by the LDLR and LRP (remnant) receptors? How many isoforms does it exist as? What are its primary responsibilities in terms of clearance?

Answer 11

Apo E; LRP responsible for uptake of chylomicrons and VLDL, along with IDL; need apoE to clear LPs after meal and clearance of VLDL and IDL before conversion to LDL; 3 isoforms, with E3 most common

Question 12

At the start of chylomicron metabolism, what protein is required? What is loaded into what?

Answer 12

REquires microsomal trigylceride transfer protein (MTP); loads Apo B-48 with lipid

Question 13

Where was this chylomicron made? Where does it go, and what happens upon exit from the plasma membrane? In the blood, what does the chylomicron pick up?

Answer 13

Made in the SER; it was transferred to the Golgi and packaged in secretory vesicles; it will enter the lymphatics, then the blood, and will then get Apo C-II and Apo E

Question 14

What does apo C-II activate? When activated, what does this enzyme do? What do the products of this enzyme action do?

Answer 14

Activates Lipoprotein lipase, which attaches to capillary walls; it hydrolyzes TAG to FA’s and glycerol; FA’s stored or used for energy, glycerol used by liver for lipid syntehsis or gluconeogenesis

Question 15

Once LPL acts, what happens to the particle? Where does Apo C-II go?

Answer 15

Particle decreases in size, increases in density; Apo C-II goes to HDL and makes chylomicron remnant

Question 16

What happens to the chylomicron remnant? What process takes it in? What happens once inside the cell?

Answer 16

Taken up by liver by Apo-E binding to lipoprotein receptors; endocytosis; lysosomal hydrolytic enzymes degrade remnant components and receptors are recycled

Question 17

What is the structure of LPL? What is the pathology of LPL deficiency? When is LPL expression increased/decreased in adipose tissue and muscle?

Answer 17

It is an anti-parallel homodimer with an N terminal with a lipid to bind to C-terminal domain; familial LPL deficiency and risk of pancreatitis; in the fed state, one expects LPL expression to increase in adipose tissue and decrease in muscle, the reverse with fasting

Question 18

Where are VLDLs made? What do they do? What can be seen as VLDL is converted to LDL in the blod?

Answer 18

In the liver; they carry lipids from the liver to the peripheral tissues; you can see IDL or VLDL remnants during the transition

Question 19

If a patient is homozygous for E2, what’s the problem?

Answer 19

Can’t clear chylomicrons or IDL because of poor binding to receptors of Apo E-2 (familial type III hyperlipoproteinemia)

Question 20

What’s the pathology with the E-4 isoform?

Answer 20

Increased susceptability and decreased age of onset for late-onset Alzheimer’s

Question 21

What does Cholesterol Ester Transfer Protein do? What determines the rate of exchange?

Answer 21

Catalyze excahnge of TAG from VLDL with cholesterol ester from HDL; need more TAG containing lipoprotein particles

Question 22

What do LDL particles do? What receptors do they bind? What assists with entrance of LDL? What is a deficiency of the LDL recpetor related with?

Answer 22

Their function is to take cholesterol to the peripheral tissues and return it to the liver; bind LDL receptors that recognize apo B-100 and apo E; need clathrin to help form a coated vesicle; elevated plasma LDL-cholesterol and type II hyperlipidemia)

Question 23

What happens when the coated receptor enters the tissue? What drops pH of the endosome? What happens to the receptor and the endosome? What deals with the LDL?

Answer 23

Lose the clathrin and fuse with other vesicles to form endosomes; need an ATP dependent proton pump; this uncouples recpetor and LDL particle and separate into compartment for Uncoupling receptor and ligand (CURL); lysosomal hydrolases deal with the LDL to release amino acids, fatty acids, cholesterol, and phospholipids

Question 24

What happens with an oversupply of cholesterol in the liver regarding HMG CoA reductase and liver LDL receptor expression? What happens with ACAT?

Answer 24

In both cases, you would decrease the expression; ACAT activity increases

Question 25

What hapens if the cholesterol is not needed immediately for synthetic or structural purpose?

Answer 25

Esterify by Acyl CoA:cholesterol acyl transferase (ACAT); youget a cholesterol ester

Question 26

What are the six components of the LDL receptor?

Answer 26

LDL binding region; epidermal growth factor-like domain and a trasducin beta subunit-like domain forming a propeller (this is what causes release of LDL from receptor); N-linked and O-linked oligo domains; transmembrane domain; intracellular domain to associate with the clatrhin coated pit for endocytosis

Question 27

How do you form HDLs? What are some qualities and functions?

Answer 27

You need addition of lipids to apo A-1; it serves as a supplier of apo C-II and Apo E and take up cholesterol from peripheral tissues and returns it to the liver as cholesterol esters; also big one is reverse cholesterol transport

Question 28

What happens as HDL picks up cholesterol esters?

Answer 28

HDL converts from discoidal nascent HDL to cholesterol poor HDL3 and then CE-rich HDL2 particle that carries CE to the liver.

Question 29

What is activated by Apo A-I and produces cholesterol esters and lysophosphatidyl choline?

Answer 29

Lecithin:cholesterol acyl transferase

Question 30

What is reverse cholesterol transport? How does cholesterol leave the peripheral tissues, and how do cholesterol esters enter the liver?

Answer 30

Transfer of cholesterol from peripheral cells to HDL and from HDL to liver; efflux of cholesterol from peripheral tissues is catalyzed by ABCA1, and uptake of CE’s involve scavenger receptor class B type 1 that bind HDL on the hepatocyte surface

Question 31

What degrades TAG and phospholipids? What else does this do?

Answer 31

Hepatic lipase; participate in conversion of HDL2 to HDL3

Question 32

What receptor enables macrophages to chew up large amounts of oxidized LDL? Are they regulated by intracellular cholesterol concentrations? What do they form and participate in?

Answer 32

Scavenger receptor, specifically A; no they are not, so they can become foam cells and form fatty streaks to participate in plaque formation

Question 33

What cells migrate to contribute to plaque formation and thinning of the fibrous cap? What does this ultimately lead to?

Answer 33

Vascular smooth muscle cells migrate from the tunica media to the intima and can promote cap rupture; thrombus and possible MI