4: Hsf B5: Lipoproteins

Front 1

What is the ideal healthy fasting level of:

1) Total cholesterol
2) LDL - cholesterol
3) HDL - cholesterol
4) Triglycerides

Back 1

1) <200 mg/dl
2) < 100 mg/dl
3) > 60 mg/dl
4) < 150 mg/dl

Front 2

What are the major energy source for cells?

Back 2

Triglycerides

Front 3

Where is a majority of cholesterol made?

Back 3

Liver

Front 4

What are the three most abundant lipids? What are their functions?

Back 4

1) Triglycerides - major energy source for cells
2) Phospholipids - major component of cell membranes
3) Cholesterol - cell growth/division, membrane repair, steroid hormone production, bile salts. **Majority made in the liver**

Front 5

1) Structure of triglycerides? What kind of energy storage do they provide?
2) Structure of phospholipids?

Back 5

1) 3 fatty acids connected to glycerol via **ester** linkage. High density energy storage.
2) 2 fatty acids, glycerol, phosphate, polar head group

Front 6

1) What does lecithin cholesteral acyltransferase do?
2) What are the sources of cholesterol in the diet? Biosynthesis?
3) Where does degradation of cholesterol occur?

Back 6

1) Converts free cholesterol into cholesterol esterase
2) Diet - animal fat, biosynthesis - primarily in the liver from acetyl-coA (which is inhibited by LDL uptake)
3) **Only in the liver**

Front 7

1) What are the two forms of fatty acid, and what is the % of each?
2) What are free fatty acids derived from?

Back 7

1) *Free unesterified fatty acid form** - 2-5%. 95% in form of fatty acid esters
2) **Hepatic/adipose tissue triglycerides (intracellular hydrolysis), circulating lipoproteins (digested by lipoprotein lipase)**

Front 8

1) What are the two fuels in blood?
2) Oxidation of these fuels are used inversely. Explain.

Back 8

1) Glucose, fatty acids
2) Glucose is oxidized after eating, converted into glycogen. Fatty acids are oxidized during fasting.

Front 9

Explain the storage of FFA during the feed state and the mobilization during fasting.

Back 9

1) Feed state - insulin inhibits hormone sensitive lipase, stimulates triglyceride synthesis, stimulates LPL (receptor mediated lipoprotein uptake). *Result = storage of triglycerides*

2) Fasting - Drop in insulin activates hormone sensitive lipase, which will hydrolyze triglycerides in in adipocytes

Front 10

1) What are lipoproteins made of?
2) What do they do? Are they soluble?
3) Describe the structure of a lipoprotein

Back 10

1) Lipids + apolipoproteins
2) Insoluble, so they transport lipids.
3) Spherical soluble particles with nonpolar lipids in core (TG and cholesterol esters), polar aspect is towards the aqueous phase.

Front 11

What are apoproteins and what are their functions?

Back 11

Proteins associated with lipoproteins for structure, binding sites for receptors, and activators for lipid metabolism. They direct the fate of lipoproteins.

Front 12

What are the five types of lipoproteins? List them in order of increasing density.

Back 12

1) Chylomicron/chylomicron remnant
2) VLDL
3) IDL
4) LDL
5) HDL (good, and smallest)

Front 13

1) What are the larger lipoprotein particles? What is their density like? Content of triglycerides?
2) What are the smaller lipoprotein particles? What is the density like and the triglyceride content? What do they contain a greater mass of and what are they enriched in?

Back 13

1) Chylomicrons and VLDL, higher content of triglycerides and lower density
2) IDL, HDL - greater density, less triglyceride content. Most protein, most cholesterol esters.

Front 14

What is the alpha band? Pre-beta band? Beta band?

Back 14

Alpha - HDL. Pre-beta - VLDL. Beta - LDL.

Front 15

1) What factors on a lipoprotein are variable and can exchange?
2) What factors need a transfer protein?
3) What is the exception?

Back 15

1) Proteins can exchange, surface phospholipids and cholesterol can transfer
2) Cholesterol ester/triglycerides need CETP (cholesterol ester transfer protein)
3) Exception: apoB 100 and B48 (structural), can't coexist on same particle and can't exchange. Only one apoB 100 or one B48 on one particle.

Front 16

Source, apoproteins, and function of:

1) Chylomicrons
2) VLDL
3) LDL
4) HDL

Back 16

1) Gut, B48/CII/E, transports *dietary TG*. FFA -> adipose/muscle, CE -> liver via remants
2) Liver, B100/CII/E, transports endogenously *endogenously synthesized TG*. FFA -> adipose, muscle. CE -> LDL
3) Blood, B100, delivers cholesterol to peripheral muscle. CE -> liver, peripheral cells
4) Liver, A1/CII/E, **reverse cholesterol transport**. Removes "used" cholesterol from tissues, donates apolipoproteins to CM and VLDL.

Front 17

1) Where do apo100 and apoB48 come from?
2) How does the size of apoB48 compare to apoB100?
3) What produces B48, and what is it produced as a result of?

Back 17

1) Same gene
2) B48 is 48% of B100 in size
3) **Intestine exclusively produces it in response to editase, a mRNA editing enzyme. Results in sub of T for C to create premature stop codon

Front 18

What are the largest, most triglyceride-rich and least dense lipoproteins? How long do they last and what state are they nearly absent in?

Back 18

Chylomicrons. Short-lived, nearly absent in fasting state

Front 19

Chylomicrons:

1) Where are they assembled and where do they go after they're assembled?
2) What apoprotein do they have? Where do they acquire their other apoproteins?
3) What is the main function?

Back 19

1) Intestinal mucosa -> lymphatics -> blood via thoracic duct
2) B48, acquire others through HDL
3) **Transport dietary triglycerides** to adipose tissue for storage, muscles for energy

Front 20

Chylomicrons:

1) What does the size of the particle depend on?
2) What other proteins does it pick up and where?
3) What does TG composition resemble?
4) How is it assembled? How do they get out of the small intestine after they're synthesized?

Back 20

1) Amount of available triglyceride
2) Apo A, C, E in plasma
3) Dietary intake
4) Monoglycerides and fatty acids passively absorbed, repackaged into triglyceride in the SER, golgi adds phopholipids and cholesterol to make chylomicrons. Out through secretory vesicles

Front 21

VLDL:

1) What is the makeup of the main lipoproteins in it?
2) What is its function?
3) What are they produced by?
4) What acts upon them to liberate FFA?
5) What is the major structural apoprotein?
6) What does lipolysis of VLDL create?

Back 21

1) Mostly TG with lots cholesterol ester and cholesterol
2) Transport *endogenously* synthesized TG to extra hepatic tissues (storage or energy)
3) Liver
4) LPL liberates FFA from VLDL
5) Apo100
6) Smaller VLDL remnants that are **more cholesteral ester rich**

Front 22

1) Describe VLDL assembly
2) What are the three sources of fatty acids for VLDL
3) Where is VLDL released after it's manufactured?

Back 22

1) Hepatocytes uptake plasma lipoproteins and secrete VLDL
2) Plasma FFA from albumin, triglyceride rich lipoproteins that have undergone receptor-mediated endocytosis, synthesized de novo in liver
3) Space of Disse

Front 23

IDL:

1) Where are they made from?
2) What is the main structural apoprotein?
3) What are they enriched with?

Back 23

1) 50% of VLDL -> IDL
2) ApoB100
3) Cholesterol esters

Front 24

LDL:

1) Main function?
2) What lipoproteins are they rich in?
3) 95% of protein is what apoprotein?
4) 70% of the cholesterol in plasma is from what?

Back 24

1) **Deliver CHOLESTEROL to extrahepatic tissue**
2) Cholesterol
3) B100
4)** Lipolysis of VLDL**

Front 25

What is the best single predictor of increased rick for atherosclerosis?

Back 25

High plasma LDL or apoB100

Front 26

1) 50% of small VLDL is converted to?
2) IDL and LDL are mostly made from?
3) What happens during delipidation?

Back 26

1) IDL and LDL
2) VLDL remnants
3) Become depleted in triglycerides, enriched in cholesterol esters

Front 27

1) What happens in the endogenous pathway of lipoprotein metabolism?
2) What happens in the exogenous pathway of lipoprotein metabolism?
3) What happens during HDL metabolism?

Back 27

1) Lipids synthesized by liver
2) Chylomicron pathway - dietary fat
3) Apoprotein transfer, cholesterol ester transfer, **reverse cholesterol transport)**

Front 28

Lipoprotein lipase:

1) What is the site of action?
2) What is the activator?
3) Function?

Back 28

1) Capillary walls
2) Apo CII
3) Gets FFA from triacylglycerols in chylomicrons, VLDLs for adipose and muscle

Front 29

ACAT:

1) What is it?
2) Where is its site of action?
3) What is its activator?
4) What does it do?

Back 29

1) Acyl-CoA:cholesterol acyltransferase
2) Inside cells
3) Free cholesterol
4) Cholesterol ester storage

Front 30

LCAT:

1) What is it?
2) Site of action?
3) Activator?
4) Function?

Back 30

1) Lectin:cholesterol acyltransferase
2) Blood
3) Apo A1
4) Cholesterol extraction from cells -> HDL carries CE for liver clearance by bile acids

Front 31

CETP:

1) Site of action
2) Activator
3) Function

Back 31

1) Plasma membrane
2) Apo A1 (cholesterol induced)
3) Flips cholesterol and lecithin to outer layer of lipid bilayer for LCAT action in blood

Front 32

Describe the exogenous pathway of lipid transport, starting with the assembly of chylmicrons.

Back 32

1) ApoB48 aids with chylomicron assembly
2) Chylomicrons -> lymph system -> capillaries
3) Pick up apo CII, E from HDL
4) LPL removes FFA, carries it to tissues. Chylomicron remnants take cholesterol to liver.
5) Chylmicron remnants lose CII to HDL.
6) Liver: apoE receptor takes up remnants to deliver cholesterol

Front 33

Describe the endogenous pathway of lipid transport

Back 33

1) B100 helps assemble VLDL
2) VLDL acquires CII/E from HDL
3) LPL hydrolyzes triacylglycerols, FFA -> nonhepatic tissue, LDL -> tissues
4) CII/E released to HDL (so LDL isn't taken into liver right away). apoB100 binds, takes LDL to receptor in cell to deliver cholesterol
6) HDL scavengers cholesterol
7) ApoE of HDL binds liver receptor
8) Cholesterol uptake in liver, secreted as bile acids

Front 34

1) Function of HDL
2) What organ takes it up and degrades it
3) What happens to the cholesterol is carries?

Back 34

1) Carried "used" cholesterol back to the liver
2) Liver takes up HDL and degrades it
3) Excreted as bile salts or repackaged in VLDL

Front 35

What is cholesterol synthesis in the liver regulated by?

Back 35

Cholesterol arriving from HDL and dietary cholesterol from chylomicron remnants

Front 36

How do statins affect HDL and LDL?

Back 36

Raise HDL, lower LDL

Front 37

1) What is lipoprotein clearance?
2) How long does it take to remove a) large VLDL b) small VLDL and IDL 3) LDL

Back 37

1) Irreversible removal from plasma
2) a) minutes b) 1-2 hours c) 2-3 days (loss of apoE, and affinity for LDL receptors allows it to gain access to the tissues)

Front 38

What does LDL need to lose to gain access to the tissues?

Back 38

ApoE, loss of affinity for LDL receptors

Front 39

Why is enrichment of ApoE important?

Back 39

It increases the affinity for lipoprotein receptors

Front 40

What three things deliver cholesterol to the liver to clear it, and what receptors do they bind to?

Back 40

1) Chylomicron remnant -> E receptor
2) Mature HDL -> E receptor
3) LDL -> B100 receptor

Front 41

1) What two things clear plasma LDL?
2) What is preferentially used as opposed to de novo cholesterol synthesis?
3) 70% of LDL clearance is mediated by what receptors?

Back 41

1) 40% liver, 60% extrahepatic tissues
2) LDL cholesterol
3) LDL receptors, 30% by scavenger receptors

Front 42

1) Where is the LDL receptor found?
2) What happens after LDL is taken into cell?
3) What does LDL cholesterol uptake regulate?
4) What happens to mutations in LDL receptors? What disease process does it accelerate?

Back 42

1) Clathrin coated pits
2) Degraded, releasing lipid cargo
3) Downregulates cell production of cholesterol, downregulates LDL receptor synthesis
4) Causes increased plasma LDL levels (increased cholesterol levels), accelerates atherosclerosis (familial hyperlipidemia)

Front 43

What is corneal arcus associated with?

Back 43

Hyperlipoproteinemia types 2, 3. In males <40 yrs, predictive of increased risk of coronary artery disease

Front 44

What is tendon xanthoma typically found in?

Back 44

Type 2a hyperlipoproteinemia

Front 45

1) What is the normal physiology of atherogenesis?
2) What goes wrong to cause atherosclerosis?
3) What causes it?

Back 45

1) Lipoproteins continually enter arterial wall, acted on by LPL. Equilibrium exists between entry of plasma proteins, lipoproteins into the artery wall and exit to plasma/catabolism by arterial cells
2) Equilibrium shifts to accumulation of lipoprotein, mostly b/c deficiency of LDL receptors.
3) Inherited, or diet in high cholesterol, high saturated fat diet

Front 46

What is the consequence of oxidized LDL formation?

Back 46

1) Uptake by scavenger receptors on macrophages that are on arterial walls -> foam cells
2) Elicits cholesterol deposition in artery walls
3) Atherosclerosis develops

Front 47

Describe the formation of arterial plaque.

What does LDL do to become oxidized?

Back 47

1) Oxidized LDL stimulates endothelial cells, releasing chemokines and cytokines to recruit monocytes into arterial wall.
2) Macrophages become full of lipid, enlarged - foam cells
3) Foam cells form fatty streak - part of atherogenic plaque

Increased residence time in plasma, increased modification/oxidation of LDL as a result