metabolism of lipoproteins

Explain lipoproteins and how triglycerides and cholesterol are transported in plasma

lipoproteins are like the bubble that they travel in. There are phospholipids (the little head with the tails) making a “shell” and the core/inside is where the TGs and cholesterol are

explain the TGs, cholesterol, and proteins in relation to their densities.

the more triglycerides a lipoprotein has the ___ its density

TGs and cholesterol: low density

proteins: high density

the more triglycerides or cholesterol a lipoprotein has the lower its density

What are the two main functions of a lipoprotein?

• solubilize the insoluble lipids for transport in the blood

• transport both dietary lipids and endogenously synthesized lipids

____ transports dietary lipids and fat-soluble vitamins from the intestine to the liver and other tissues

chylomicrons

____ transport endogenous synthesized lipids from liver to other tissues

VLDLs

____ deliver cholesterol from the liver to tissues with more cholesterol needs (like adrenals, sex glands, etc.)

LDLs

_____ transport cholesterol from peripheral tissues back to the liver

HDLs

Put the classes of lipoproteins in order from biggest to smallest and least dense to densest

chylomicron (largest and least dense)

VLDLs (very low density)

IDLs (intermediate density)

LDL (low density)

HDL (smallest and most dense)

short version: chylomicron → VLDL → IDL → LDL → HDL

What is an apoprotein and what are its 3 functions? (ex: apoB-48, apoB-100, etc.)

an apoprotein is the protein part of a lipoprotein

functions: structural components, regulate enzyme activity, and act as ligands for receptors

Which pathway?

distributes dietary triglycerides and cholesterol to the liver and peripheral tissues

chylomicron/chylomicron remnant pathway

Which pathway?

transports triglycerides and cholesterol out of the liver to the peripheral tissues

VLDL, IDL, LDL pathway

Which pathway?

transports cholesterol form peripheral tissues back to the liver

nascent/mature HDL pathway

After they are synthesized, ___ are secreted into the lymphatic system and enter the blood through the thoracic duct

chylomicrons

Which apoprotein is specific to chylomicrons?

ApoB-48

lipids are loaded onto ApoB-48 by ____ in the synthesis of chylomicrons.

a deficiency of this can lead to _____

microsomal triglyceride transfer protein (MTP)

MTP deficiency → abetalipoproteinemia

Which apoprotein is produced by the RNA editing of theApoB-100 gene. What is the edit?

apoB-48

a C is edited to a U to create a stop codon

What enzyme hydrolyzes the TGs that are in the chylomicrons? What does this enzyme do?

lipoprotein lipase

allows the TGs to be released as free fatty acids in the tissues

What apoproteins are transferred from HDLs to the nascent chylomicrons to form mature chylomicrons?

ApoC-II and ApoE

Which apoprotein stimulates lipoprotein lipase (LPL) that allows the TGs to be released from the chylomicron as free fatty acids?

ApoC-II

insulin stimulates _____ in adipose tissues after a balanced meal to ____

insulin stimulates lipoprotein lipase (LPL) which allows the dietary TGs in the chylomicrons to be released at free fatty acids in the tissues

LPL (lipoprotein lipase) is activated by ____

ApoC-II

After LPL (lipoprotein lipase) allows the TGs to be released form the chylomicron, what happens to the empty chylomicron?

it becomes a chylomicron remnant

Chylomicron remnants ____ in size and ____ in density because _____.

they decrease in size and increase in density because they have released their TGs

After a chylomicron releases its TGs and becomes a chylomicron remnant, what else happens?

the ApoC-II that attached to it to make it mature leaves and goes back to the HDLs

What happens to the chylomicron remnants?

they get taken up by hepatocytes (endocytosed) and then fuse with lysosomes and get hydrolyzed

pancreatic failure (less digestive enzymes made), lack of bile salts, and intestinal disease can all lead to what?

fat malabsorption (dietary lipids- chylomicrons)

steatorrhea with bulky fatty appearing stools is a result of what?

fat malabsorption (dietary lipids- chylomicrons)

Fat malabsorption and a defect in the chylomicron pathway can have what effect on vitamins?

we get a decrease in fat soluble vitamin absorption (D,E,A,K) 

Apo(a)/Lp(a) is structurally similar to _____

plasminogen

high levels of ___ are associated with increased risk of coronary heart disease (explain)

What is linked to these high levels?

Lp(a); because it has apo(a) which is structurally similar to plasminogen, this slows the breakdown of clots because it competes with plasminogen for binding of fibrin

high dietary trans fats are associated with increased levels of Lp(a)

____ reduces Lp(a) and LDL and raises HDL

niacin

HDLs bind the ____ receptor on hepatocytes and ___ happens

scavenger receptor (SR-B1) and they transfer cholesterol and cholesterol esters into the liver cell (hepatocyte), they have no endocytosis, then then HDL dissociates after it “drops the kids off” and re-enters the circulation

To become a mature VLDL, what apoproteins are involved?

they accept apoE and apoC-II from HDL

_____ is the structural apoprotein for VLDL

ApoB-100 (no change from C to U to make stop codon)

What enzyme is responsible for digesting the TGs of VLDL?

lipoprotein lipase (LPL)

VLDL becomes _____ or _____ after losing its TGs

VLDL remnant or IDL

IDL is taken up the liver hepatocytes via _____

apoE receptor 

IDL can be further metabolized and become _____

LDL

LDL binds to the LDL receptor via ______

apoB-100

excess and oxidized LDL can _____ the uptake by the liver and is taken up by _____

can saturate the uptake by the liver and is taken up by macrophages

Excess LDL is taken up by macrophages and forms ____ then _____ leading to ____

foam cells then plaques that lead to atherosclerosis 

inside the cell, free cholesterol can be re-esterified via ____

ACAT (acyl CoA cholesterol acyltransferase

_____ cannot release cholesterol from the _____ so the cholesterol builds up in the ____ and leads to cell death that can result in early death of the pt

build up in the lysosome (because it cant get released form the lysosome)

Niemann-Pick type C disease

Explain the shape difference between a nascent HDL particle (immature) and a mature HDL particle

nascent: disk shaped

mature: globular shaped

mature HDL is also called ___ and they accumulate ___ as they mature

HDL3

accumulate cholesterol

HDL can be synthesized in the ___ and ____

liver and intestines

____ plays a major role in reverse cholesterol transport (this transport is vasculo-protective)

HDL

cells/tissues get rid of their cholesterol by _______

reverse cholesterol transport

with reverse cholesterol transport, ____ flips cholesterol from the inner leaflet of the plasma membrane to the outer leaflet so HDL can come by and pick it up

ABC1 (aka ABCA1)

What two enzymes are required for HDL to pick up cholesterol from the extrahepatic cells/tissues

LCAT (lecithin cholesterol acyl transferase) and CETP (cholesterol ester transfer protein)

LCAT is activated by _____

apoA-I

What traps cholesterol in the HDL?

LCAT

What transfers cholesterol esters to VLDL in exchange for triglyceride and phospholipids in reverse cholesterol transport?

CETP (cholesterol ester transfer proteins)