T13 - Lipoprotein Metabolism

Question 1

Give an example of a hydrophilic amphipath. (2)

Answer 1

fatty acids

phospholipids

Question 2

Give an example of a hydrophobic amphipath.

Answer 2

cholesterol

Question 3

What is the composition of mixed micelles?

Answer 3

phospholipids

long chain fatty acids

MAGs

bile acids

Question 4

Describe the relative orientations of the components of mixed micelles.

Answer 4

hydrophobic portions of PLs, fatty acids, and MAGs oriented toward center and surrounded by amphipathic bile acids

Question 5

Describe the common, generic structure of all lipoproteins.

Answer 5

hydrophobic TG + CE core

trace quantities of fat-soluble vitamins

surface with amphipathic molecules (unCE + PLs) + amphipathic apolipoproteins

Question 6

What are the two criteria by which lipoproteins are classified?

Answer 6

classification based on relative size and density

Question 7

What is the density of plasma?

Answer 7

1.006 g/mL — slightly higher than water because of presence of proteins

Question 8

List the relative densities of cholesterol, CE, PL, protein, and TG.

Answer 8

cholesterol/CE/PL = 1.000

TG = 0.900

protein = 1.200

Question 9

What are the six major classes of lipoproteins?

Answer 9

HDL

LDL

VLDL

CM

IDL

CMr

Question 10

Describe HDL.

Answer 10

small particles that are rich in protein + CE and poor in TG

Question 11

Describe LDL.

Answer 11

less protein but mostly CE and slightly higher TG

Question 12

Describe VLDL. (2)

Answer 12

large amounts of TG, some CE, and little protein

density below plasma density

Question 13

Describe CM.

Answer 13

even more TG relative to CE (>10:1 ratio) and very little protein

Question 14

Describe IDL.

Answer 14

have similar amounts of TG and CE

Question 16

How are IDLs produced?

Answer 16

produced from metabolism of VLDL particles

Question 17

Describe CMr.

Answer 17

remnants of chylomicrons rich in CE and TG

Question 18

What is the alternative pathway for hepatic CM uptake if hepatic LDL receptors are nonfunctional?

Answer 18

LRP mechanism — CMr can still be cleared normally even in patients without functional LDLR (i.e. familial hypercholesterolemia)

Question 19

What is the principal function of chylomicrons?

Answer 19

to deliver TG to peripheral tissues

Question 20

What are the physical characteristics of VLDL? (3)

Answer 20

TG-rich but lower TG:cholesterol ratio (5:1) than that present in CMs (20:1)

VLDLs smaller than CMs (80 nm vs. 500 nm)

VLDL contains 1 copy of ApoB-100 but multiple copies of ApoAI, ApoCII, and ApoE

Question 21

Where does VLDL synthesis occur?

Answer 21

ER of hepatocytes

Question 22

Describe the steps of VLDL synthesis. (3)

Answer 22

made in ER → undergoes lipidation → secreted into blood → acquires multiple copies of ApoE + ApoCII from HDL

Question 23

Which ApoB variant does VLDL contain?

Answer 23

ApoB-100 (remember, because VLDL is made in the liver, it can only have the B-100 variant)

Question 24

What protein/enzyme does VLDL encounter as it circulates through the body?

Answer 24

encounters lipoprotein lipase (just like CMs do) and undergo breakdown such that most of the VLDL’s TGs are delivered to peripheral tissue

Question 25

What does VLDL become after interaction with lipoprotein lipase?

Answer 25

becomes a VLDL remnant = intermediate density lipoprotein (IDL)

Question 26

How are VLDL remnants cleared?

Answer 26

through two pathways: 1) 50% of the time, cleared by LDLR-mediated endocytosis in the liver 2) the other 50% of the time, VLDL remnant further metabolized into LDL, which contains a single ApoB-100

Question 27

What enzyme is responsible for the conversion of IDL to LDL?

Answer 27

hepatic lipase

Question 28

Hepatic lipase is responsible for what activity?

Answer 28

conversion of IDL into LDL i.e. conversion of VLDL into LDL

Question 29

Where does the formation of LDL from VLDL occur?

Answer 29

vascular space

Question 30

How is LDL cleared from circulation?

Answer 30

in liver or peripheral tissue via LDLR-mediated endocytosis

Question 31

What structure on LDL serves as the ligand for LDLR-mediated endocytosis?

Answer 31

ApoB-100

Question 32

Differentiate between the rate of clearance of LDL and VLDLr.

Answer 32

VLDLr uses ApoE for uptake LDL uses ApoB-100 for uptake ApoB-100 has lower affinity than ApoE for LDLR therefore, VLDLr cleared faster than LDL

Question 33

(T/F) All LDL is cleared by the liver.

Answer 33

**False.** 20% of the LDL is taken up by extrahepatic tissues.

Question 34

What are the values of VLDLr and LDL in a normal individual?

Answer 34

VLDLr = 10/20 mg/dl (cleared rapidly) LDL = 90-100 mg/dl

Question 35

What is the principal composition of HDL?

Answer 35

high amounts of ApoAI with smaller amounts of ApoCII and ApoE (basically, mostly protein)

Question 36

Where is HDL synthesized?

Answer 36

in the liver and small intestines

Question 37

How is HDL initially synthesized?

Answer 37

as disc-like particles w/ unesterified cholesterol, phospholipids, and ApoA-I

Question 38

Describe the steps of HDL particle formation.

Answer 38

disc-like particle forms → unesterified cholesterol esterified to long-chain fatty acid via LCAT enzyme → esterified cholesterol forms HDL core

Question 39

Which enzyme is responsible for HDL particle formation?

Answer 39

lecithin-cholesterol acyltransferase (LCAT)

Question 40

(T/F) Cells in the body are capable of degrading sterols.

Answer 40

**False.** No cells in the body can degrade sterols.

Question 41

What is the only cell type that does NOT continuously synthesize cholesterol from acetyl CoA?

Answer 41

RBCs

Question 42

What are the two mechanisms by which HDL particles pick up cholesterol in peripheral tissue and deliver it back to the liver?

Answer 42

(1) **CETP**: cholesteryl esters in HDL transferred to CM/VLDL/LDL (all ApoB lipoproteins) via enzyme cholesterol ester transfer protein (CETP) and cleared by the liver via LDLR-mediated endocytosis (2) **SR-BI**: ApoAI interacts with SR-BI (a.k.a. SCAR-B1) on hepatocyte which allows direct transfer of cholesterol esters from HDL to hepatocyte cytosol

Question 43

How is cholesterol excreted by the liver and small intestines? (2)

Answer 43

some of the cholesterol that returns to the liver is converted to bile acid and secreted into bile alternatively, cholesterol is secreted directly into bile by ABCG5/ABCG8

Question 44

Describe the levels of CM, VLDL, HDL and LDL in fasting individuals.

Answer 44

in fasting individuals: CM and VLDL low HDL and LDL high

Question 45

A mutation in CETP would have what effect on HDL levels?

Answer 45

mutation in CETP → high HDL levels

Question 46

An increase in triglyceride levels has what effect on HDL levels?

Answer 46

increase in triglycerides → lower HDL levels

Question 47

Why are levels of CM and VLDL so low in fasting blood samples?

Answer 47

CM and VLDL are low in fasting blood because they’ve been taken up/cleared by the liver

Question 48

What is the effect of having a non-functional LDL receptor for the clearance of exogenously-derived lipoprotein particles?

Answer 48

No effect. LRP is a form of redundancy that can clear LDLs. LRP binds ApoE instead of ApoB. LRP, unlike LDL receptors, is not regulated and is constitutively on.