42-PLASMA LIPOPROTEINS – Dr. Groseclose Flashcards
List the 5 classes of plasma lipoproteins and describe the origin and function of each.
1) Chylomicrons synthesized from dietary fat ingested by the intestine, as the largest and least dense, chylomicrons are absorbed by peripheral endothelial cells. Have apo B-48.
2) VLDL synthesized in the liver and modified during circulation by removal of a lipid. Have apo B-100, apo E and apo C-11.
3) IDL are VLDL particles depleted of their lipids. Apo C-11 is depleted.
4) LDL is a product of the removal of lipid from IDL. Endocytosed by tissue with LDL receptors by recognition of apo B-100.
5) HDL synthesized in plasma from components of other lipoproteins. Can remove cholesterol from plasma by recognition of apo A-1 by enzyme LCAT. Has special scavenger receptor class B type 1 (SR-B1) that allows cholesterol to be removed and HDL to be re-released into the plasma.
Name the enzymes and proteins that are important for the metabolism of plasma lipoproteins and describe the role of each. Which apoprotein(s), if any, mediates the interaction of these enzymes with lipoproteins?
1) Lipoprotein lipase interacts with chylomicron and VLDL via apo C-II to breakdown triacylglycerols to give 3 fatty acids + glycerol (good for storage)
2) Hepatic lipase breaks triglycerols (or phospholipids) into 2 fatty acids + 2-monoacylglycerol (all are absorbed).
3) Lecithin:Cholesterol Acyltransferase (LCAT), made in the liver, esterifies lecithin to 3’ OH of cholesterol to make lysolecithin and cholesteryl ester (the most hydrophobic type of compound).
4) ATP binding Cassette transporters (ABCA1, ABCGs): mediates transport of cholesterol, phospholipids and other metabolites from cells TO lipid-depleted HDL apilipoproteins. !!Essential for, and is the rate-limiting step of, the formation of HDL.!!
Important Proteins: active in transport
1) Cholesteryl Ester Transfer Protein (CETP): Mediates the exchange of cholesterol esters with other particles (like triacylglycerols.
2) Phospholipid Transport Protein (PTP)
Note: LCAT is activated by apo A1
Describe the structure of a generalized lipoprotein and list the contents of core and coat.
Lipoproteins consist of triglycerides, cholesterol, cholesterol esters, phospholipids and proteins. The core consists of cholesterol ester and triacylglycerols surrounded by a phospholipid coat with unesterified cholesterol on the very outside. The coat consists of the (apo)proteins that mediate the interaction of the coat with other enzymes/receptors.
What are the meanings of the terms “good cholesterol” and “bad cholesterol” and to which plasma lipoproteins do they refer?
HDL is “good cholesterol” in that it participates in reverse transport of cholesterol from the tissues into the liver for disposal or reuse. HDL is not only dependent on it’s concentration in circulating blood also on it’s biological ‘quality’.
LDL is “bad cholesterol” in that increased levels of LDL are associated with heart disease.
Contrast the functions of the LDL receptor and scavenger receptor B1 (SR-B1).
The SR-B1 receptor holds onto HDL as cholesterol esters are removed (selective uptake) from the core and then releases the cholesterol-free HDL back into the plasma. Not involved in endocytosis.\
The LDL receptor recognizes apo E and thus internalizes lipoprotein cholesterol to cells via receptor-mediated endocytosis.
What apolipoprotein is condsidered a part of the coat that surrounds LDL?
Apolipoprotein B-100
What is special about hepatic lipase?
It is exclusive of its enzymic activity and the body of it’s protein tends to mediate the interactions of lipoportein particles with receptors
What is lipoprotein(a), and why is it of special medical interest?
Lp(a) is a varient of LDL with an additional protein, apo(a), linked by a sulfhydryl bond to apoB-100.
It is of special medical interest because it has been shown that lp(a) in plasma is an independent risk factor for atherosclerosis and consequent heart attack and stroke. [in short it’s presence shows a higher likelihood for heart attack and stroke]
The ability of apo(a) to interfere with fibrinolysis, therefore it might prevent the dissolution of clots.
Name and describe the lipids that are associated with plasma lipoproteins
- LDL is associated with Apolipoprotein B-100
- HDL is associated with Apolipoproteins A-I, A-II, and E
- VLDL is associated with Apolipoproteins B-100, C-II and E
- IDL is associated with Apolipoproteins B-100, C-II and E
- Chylomicron is associated with apolipoproteins B-48, C-II and E
- Remnant chylomicrons are associated with only B-48 and E (having C-II stripped)
- Lp(a) has apolipoprotein(a) linked to apolipoprotein-B100 via sulfhydryl bond
Describe the endogenous and exogenous pathways of lipid transport
Exogenous pathway: (How dietary fat gets into the system). Dietary fat enters to the intestines where it is broken down by bile acids and cholesterol into Chylomicrons (which has ApoE, C-II, and B48) . These traverse through capillaries, where it is actded on by lipoprotein lipase to produce fatty acids that will be used by adipose tissue and muscle. The Chylomicron remants (now only with APoE and B-48) are taken up by the liver.
Endogeous pathway: VLDL is released by the the liver (containing ApoE, C-II, and B-100). These travel through the capillaries and are acted on by lipoprotein lipase to produce free fatty acids that will be used by adipose tissue, and muscle. The remainder, now called IDL (which has ApoE and B-100) are either taken up by LDL receptors, or covered into LDL (which only has ApoB-100), and then taken up by LDL receptors in the liver or extrahepatic tissue. If taken up by the extrhepatic tissue, HDL is formed (having ApoA-I and A-II), where it goes around the system picking up cholesterol and being acted on by Plasma LCAT to form IDL.
Describe the synthesis and metabolism of HDL. Discuss the functions of HDL, and the ways in which it interacts with other plasma components (e.g., lipoproteins, etc.) and tissues.
HDL is synthesized in the liver as apoA-I and A-II containing particle that when released from the liver into the blood acquires cholesterol from peripheral tissues via ABCs (A1). It picks up and gives off C-II and E from the plasma.
HDL as an unesterified cholesterol is esterified by LCAT, forming HDL3. It can act as a reservoir for apo C-II and E, donating them to VLDL and chylomicrons as they are encountered in circulation.
When it acquires more cholesterol esters, it is transformed from HDL 3 to HDL2.
What is Apolipoprotein M good for?
Apoprotein M mediates sphingosine-1-phosphate, which protects the endothelium
