Snf Test 4 - Lipoproteins

Front 1

What are the most abundant lipids and their functions in the human body?

Back 1

-Triglycerides: Major energy source for cells
-Phospholipids: Major component of cell membranes
-Cholesterol: Cell growth, cell division, membrane repair, steroid hormone production, bile salts, MAJORITY MADE IN THE LIVER

Front 2

Where is the majority of cholesterol made?

Back 2

In the liver

Front 3

What are triglycerides?

Back 3

3 fatty acids connected to glycerol via ester linkage

High density energy store

Front 4

What are phospholipids?

Back 4

2 fatty acids attached to a glycerol with a phosphate and polar head group

Front 5

What are the sources, biosynthesis and degradation of cholesterol and cholesterol esters?

Back 5

Diet: Only found in animal fat
Biosynthesis: Primarily in the liver from acetyl-CoA; (inhibited by LDL uptake)
Degradation: Only occurs in the liver

Front 6

What is the precentage of fatty acids presents in FREE FORM and what are they derived from?

Back 6

- Only 2-5% of fatty acid is present in FREE FORM (unesterified) - 95% are in the form of fatty acid esters

-Derived from:
*Intracellular hydrolysis of triglycerides in hepatic or adipose cells
*Lipoprotein lipase acting on circulating lipoproteins

Front 7

How are FFA stored and mobilized during feed state and fasting?

Back 7

-During feed state
*Insulin - inhibits hormone sensitive lipase and stimulates triglycerides synthesis, stimulates LPL
*Results in storage of triglycerides

-During Fasting:
*Drop in insulin activates HSL
*Triglycerides hydrolyzed in adipocytes

Front 8

What are lipoproteins?

Back 8

Lipids
Apolipoproteins
Lipids are insoluble
Lipoproteins transport lipids
Spherical soluble particle

Front 9

What are apoproteins?

Back 9

Proteins associated with lipoproteins
Functions:
-Structural
-Binding sites for receptors
-Activators or co-enzymes for lipid metabolism
*Direct the fate of lipoproteins

Front 10

How are lipoproteins classified?

Back 10

Based on buoyant density compared to physiological saline:
*Chylomicron and Chylomicron remnants
*VLDL - Very Low Density Lipoprotein
*IDL - Intermediate Density Lipoprotein
*LDL - Low Density Lipoprotein
*HDL - High Density Lipoprotein (GOOD)

Front 11

What are the characteristics of the larger lipoprotein particles?

Back 11

(Chylomicrons and VLDL)
-High content of triglycerides
-Lower density

Front 12

What are the characteristics of the smaller lipoprotein particles?

Back 12

(LDL and HDL)
-Less triglycerides
-Greater relative mass of protein
-Enriched in cholesterol esters
-Greater density

Front 13

What are characteristics common among all lipoproteins?

Back 13

-Protein content varies (number and kinds)
-Proteins can exchange
-Surface phospholipids and cholesterol can transfer
-Cholesterol esters and trigycerides need CETP (cholesterol ester transfer protein)

Front 14

What are the exception in lipoproteins?

Back 14

apoB 100 and B48 (structural)

Do not co-exist on the same particle
Only one apoB 100 or B48 molecule
Cannot exchange

Front 15

What are the source, function and apoproteins in chylomicrons?

Back 15

Source: Gut
Function: Transport of dietary TG
*FFA --> Adipose/muscle
*CE --> Liver via remnants
Apoproteins: B48, CII, E

Front 16

What is the source, function and apoproteins in VLDL?

Back 16

Source: Gut
Function: Transport of endogenously synthesized TG
*FFA --> Adipose/muscle
*CE --> LDL
Apoproteins: B100, CII, E

Front 17

What is the source, function and apoproteins in LDL?

Back 17

Source: Blood
Function: Delivers cholesterol to peripheral tissues
*CE to liver
*Peripheral Cells
Apoporoteins: B100

Front 18

What is the source, function and apoproteins in HDL?

Back 18

Source: Liver
Function: REVERSE CHOLESTEROL TRANSPORT
*Removes "used cholesterol from tissues
*Donates apolipoproteins to CM and VLDL
Apoproteins: A1, CII, E

Front 19

What is the site of action and function of Apo A1?

Back 19

Site of Action: Blood, plasma membrane

Function: Activates LCAT and CETP; binds to apo A1 receptors on cells requiring cholesterol extraction

Front 20

What is the site of action and function of Apo B48?

Back 20

Site of action: Gut

Function: Export of chylomicrons from intestinal cells

Front 21

What is the site of action and function of Apo B100?

Back 21

Site of Action: Various cells

Function: Ligand for LDL receptor; export of liver VLDL

Front 22

What is the site of action and function of Apo CII?

Back 22

Site of Action: Capillary walls

Function: Activates lipoprotein lipase

Front 23

What is the site of action and function of Apo E?

Back 23

Site of action: Liver

Function: Receptor ligand - clears remnants, IDL, and HDL

Front 24

What are the similarities and differences between apoB100 and apoB48?

Back 24

-Same gene
-ApoB48; 49% of apoB100 in size
-ApoB48 is produced exclusively by the intestine:
*result of tissue-specific expression of an mRNA-editing enzyme activity (editase)
*a substitution of thymidine (T) for cytidine (C) creates a premature stop codon

Front 25

What are chylomicrons?

Back 25

-largest of the lipoproteins
-Most triglyceride-rich
-Least dense
-Relatively short-lived
-Nearly absent in the fasting state

Front 26

What are the characteristics of chylomicrons?

Back 26

-Assembled in intestinal mucosal cells
-Enter the lymphatic system then blood via the thoracic duct
-Contain apoprotein B48; acquire other apoproteins from high density lipoproteins (HDL).
-TRANSPORT DIETARY TG:
*to the adipose tissue (storage)
*to muscles (for energy)

Front 27

How are chylomicrons assembled?

Back 27

-Size of particle depends on the amount of triglyceride available
-Enter secretory vesicles
-Picks up apo A, C and E in plasma
-TG composition closely resembles dietary intake

Front 28

What do Very Low Density Lipoproteins (VLDL) contain and transport?

Back 28

Contain:
-Nascent VLDL contain apo B100
-Contain mostly TG but with a significant amount of cholesterol and cholesterol ester

Transport:
-Endogenously synthesized TG to the extra hepatic tissues (storage or energy)

Front 29

What are the characteristics of VLDLs?

Back 29

-Large lipoproteins
-Triglyceride-rich particles
-Produced by the liver
-Acted upon by LPL to liberate FFA
-Lipolysis creates smaller, more cholesterol ester-rich VLDL remnants
-apoB100 as the major structural apoprotein

Front 30

How are VLDLs assembled?

Back 30

-Occurs in the liver:
*hepatocytes, uptake plasma lipoproteins
*hepatocytes secrete VLDL
-Three sources of the fatty acids
*plasma FFA that dissociate from albumin
*from triglyceride-rich lipoproteins that have undergone receptor-mediated endocytosis
*synthesized in the liver de novo
-ER/Golgi same as for chylomicrons
-particles enter secretory vesicles for release in the space of Disse

Front 31

What are Intermediate-density lipoproteins (IDLs)?

Back 31

-50% of small VLDL are lipolytically converted to IDL
-Contain apoB100
-Enriched in cholesterol esters

Front 32

What are the characteristics of low-density lipoproteins (LDLs)?

Back 32

-Cholesterol-rich
-95% of protein is apoB100
-70% of the cholesterol in plasma
-From lipolysis of VLDL
-Deliver cholesterol to extra hepatic tissue***
-High level of plasma LDL or apoB100 is the best single predictor of increased risk for atherosclerosis

Front 33

How are IDLs and LDLs formed?

Back 33

-50% of small VLDL are converted to IDL and LDL
-Are VLDL remnants!!!!*****
-Delipidation:
*Become depleted in triglycerides
*Become enriched in cholesterol esters

Front 34

What are the 3 pathways of lipoprotein metabolism?

Back 34

1. Exogenous/chylomicron pathway (dietary fat)
2. Endogenous pathway (lipids synthesized by the liver)
3. HDL metabolism (apoproteins transfer, cholesteryl ester transfer, REVERSE CHOLESTEROL TRANSPORT)

Front 35

What is the site of action, activator and function of Lipoprotein lipase (LPL)?

Back 35

Site of action: capillary walls

Activator: apo CII

Function: excises FFA from TAGs in chylomicrons and VLDLs for adipose and muscle

Front 36

What are the functions of HDLs?

Back 36

-HDL carries "used" cholesterol back to the liver
-Donates some CE to circulating VLDL for redistribution to tissues
-HDL taken up by liver and degraded
-Cholesterol is excreted as bile salts or repackaged in VLDL
-Cholesterol synthesis in the liver is regulated by the cholesterol arriving through HDL (and dietary cholesterol returned by chylomicron remnants).

Front 37

How do statins influence HDL and LDL levels?

Back 37

HDL: raised

LDL: Lowered

Front 38

How are lipoproteins cleared?

Back 38

-irreversible removal from plasma
-relatively rapid
-Plasma half life:
*Large VLDL - minutes
*Small VLDL and IDL - 1-2 hours
*LDL - 2-3 days (loss of apoE; loss of affinity for LDL receptors); allows to gain access to tissues

-Enrichment of apoE is important - increases affinity for lipoprotein receptors

Front 39

How is LDL cleared?

Back 39

-40% of plasma LDL is cleared by the liver
-60% of plasma LDL is cleared by extrahepatic tissues
-LDL cholesterol is preferentially used (as opposed to de novo cholesterol syn.)
-70% of LDL clearance is mediated by LDL receptorsl remainder by scavenger receptors

Front 40

What is the LDL Receptor Pathway?

Back 40

-Found in clathrin coated pits (endocytosis)
-Receptor is recycled
-The LDL is degraded releasing lipid cargo
-Cholesterol uptake down regulates the cells own production of cholesterol and down regulates LDL receptor synthesis
-Mutations in LDL receptors causes increased plasma LDL levels (ie increased cholesterol levels) accelerates progress of athersclerosis (Familial hyperlipedimias)

Front 41

What is corneal arcus?

Back 41

Associated with hyperlipoproteinemia types 2 and 3. In males <40 yrs, predictive of increased risk of coronary artery disease

Front 42

Where is tendon xanthoma found?

Back 42

Found in type 2a hyperlipoproteinemia

Front 43

What are the mechanisms of Atherogenesis?

Back 43

-accumulation of lipoprotein due to shif of equilibrium
-Common cause of accelerated atherosclerosis is a deficiency of LDL receptors
-Inherited defect or high cholesterol, high saturated fat diet

Front 44

What occurs as a result of the formation of oxidized LDL?

Back 44

1. Uptake of oxidized LDL by "scaventer receptors" on macrophages that invade artery walls

2. Elicits CE deposition in artery walls

3. Atherosclerosis/CAD can develop

Front 45

How is arterial plaque formed?

Back 45

-Oxidized LDL stimulates endothelial cells, releasing chemokins and cytokines
*recruits monocytes into the arterial wall
-macrophages become enlarged and full of lipid: foam cells
-Foam cells form the "fatty streak", part of the atherogenic plaque
-Elevated LDL
*Increased residence time in plasma
*Increased modification/oxidation of LDL