Nutrition and Cardiovascular Disease, LDL, VLDL, Chylomicrons Flashcards
Chylomicrons are released by the [ ] cells into the [ ] and contain dietary lipids including lipid-soluble vitamins.
Chylomicrons are released by the intestinal mucosal cells into the lymph and contain dietary lipids including lipid-soluble vitamins.
VLDLs are released by the [ ] into the blood and contain [ ] and [ ].
VLDLs are released by the liver into the blood and contain TAGs and cholesteryl esters.
What molecules are cleaved by lipoprotein lipase?
TAGS and VLDL remnants and are named IDL.
What is the function of LDLs?
To deliver cholesteryl esters to cells that need cholesterol. Most LDLs are taken up by the liver to prevent a high LDL blood level that can lead to CVD.
What is the function of HDLs?
They perform the reverse cholesterol transport to the liver and are filled in the blood with cholesteryl esters from cell turnover or from macrophages.
What is needed for the release of chylomicrons into the lymph?
apoB-48
Assembly of apoB-48 with lipids inside the cells needs what molecule?
MTP (microsomal TAG transfer Protein)
What is the difference between apoB100 and apoB48?
Cytidine deaminase forms the stop codon UAA leading to translation of only 48% of the mRNA (apoB-48) as opposed to apoB-100 where 100% of the mRNA is transcribed
How are nascent chylomicrons released into the lymph?
ApoB48 and MTP are needed for the assembly of and release of nascent chylomicrons into the lymph.
Where are lipoprotein lipases found?
Mainly anchored in capillaries of the heart, muscle, and adipose tissue.
Function of lipoprotein lipases:
Cleave TAGs in lipoproteins and generate free fatty acids, glycerol and lipoprotein that is a smaller size (a remnant)
What activates lipoprotein lipase in the blood?
ApoC-II (found in chylomicrons and VLDL)
What activates lipoprotein lipase in fat tissue?
Insulin is needed for activation of lipoprotein lipase which cleaves TAGs in blood and generates free fatty acids which can be stored as TAGs synthesis inside the fat cells.
Where are VLDLs formed?
Hepatocytes and VLDLs contain endogenous lipids
-This is to prevent TAG accumulation in hepatocytes and to provide substrates for lipoprotein lipase resulting in fatty acids for other cells.
What is the purpose of LDL?
To transport cholesteryl esters and deliver cholesterol to cells that need it for their plasma membranes or for steroid hormone synthesis
How do oxLDLs enter macrophages?
Via SR-A receptors which eventually lead to foam cells.
How do IDL form LDL?
TAGs in IDLs are cleaved by hepatic lipase which forms LDL
How are IDLs formed from VLDLs?
TAGs in VLDLs are cleaved by lipoprotein lipase which forms IDL.
Largest liporpotein
Chylomicrons
Ultra-centrifugation separates lipoproteins by:
Size and density: Chylomicrons > VLDL>IDL>LDL>HDL
Protein electrophoresis separates lipoproteins by
Overall charge and apoproteins
Which lipoproteins have the highest percentages of TAGS, cholesterol and proteins?
Chylomicrons
Which lipoprotein has the highest % of cholesterol?
LDL
Which lipoprotein has the highest % of protein?
HDL
Function of ApoB-48
Needed for synthesis and release of chylomicrons into the lymph
Function of ApoB100
Needed for synthesis and release of VLDLs into the blood and is needed for recognition by the LDL-receptor. ApoB-100 oxidation in LDL leads to oxLDL that enter macrophages which can lead to fatty streaks
ApoE function
Needed for recognition by the hepatic remnant receptors and for the uptake of chylomicron remnants and IDLs into the hepatocytes
Function of ApoC-II
Activates lipoprotein lipase which cleaves TAGs in chylomicrons and VLDL
Function of ApoA
Needed for the reverse cholesterol transport of HDL.
ApoB48 deficiency leads to:
Low levels of chylomicrons as the assembly and release needs apoB48
ApoB100 deficiency leads to:
Low levels of VLDLs, IDL,s and LDLs as the assembly and release of VLDLs needs apoB100
ApoE deficiency leads to :
high levels of chylomicron remnants and IDLs as the hepatic remnant receptors needs apoE for endocytosis
ApoC-II deficiency leads to:
High levels of chylomicrons and VLDLs as apoC-II is needed for activation of lipoprotein lipase
Apo A deficiency leads to:
Early degradation and very low HDL
What molecule releases free cholesterol into the blood from membranes undergoing turnover and from dying cells?
Cholesterol ABC transporters
How are cholesteryl esters formed from HDL?
Using Lecithin-cholesterol-acyl-transferase (LCAT), an enzyme synthesized in the liver and released into the blood.
LCAT needs activation by:
and uses a [ ] from phosphatidylcholine (PC) of the HDL membrane to form cholesteryl esters (CE) in the blood.
apoA-1, and uses a fatty acid from phosphatidylcholine of the HDL membrane to form cholesteryl esters in the blood.
Action of cholesteryl ester transfer protein (CETP)
CETP is a protein that forms a hydrophobic channel and connects HDL and VLDL for exchange of nonpolar lipids
Treatment for hypercholesterolemia
1) Stimulated LDL-R synthesis at low hepatic free cholesterol. Use of statin drugs that competitively inhibit HMG CoA reductase.
2) Treatment with PCSK9-inhibitor drugs when statins do not work.
What is the normal function of PCSK9?
It prevents the recycling of the LDL-receptor and leads to its degradation in lysosomes
What is lipoprotein(a)?
Very similar to LDL but it has apo(a) linked to apoB-100 by a disulfide bond. It is also a structural analog to plasminogen and may compete for the binding to fibrin. It may reduce the removal of blood clots, which could trigger MI or stroke.
Does Lp(a) reduce or increase blood clot removal?
Reduce
HDL is a [ ]-lipoprotein
alpha-lipoprotein
LDL is a [ ]-lipoprotein
beta-lipoprotein
VLDL is a [ ]-lipoprotein
pre-beta-lipoprotein
Cox-1 is a [ ] enzyme
Cox-1 is a constitutive enzyme
Cox-2 is a [ ] enzyme
Cox-2 in an inducible enzyme (inflammation)
Leukotriene A4 is produced in:
Leukocytes, platelets, mast cells, and heart and lung vascular tissues
Function of Prostacyclin
PGI2: Produced by COX-2 primarily in endothelium of vessels for vasodilation and inhibition of platelet aggregation
Celecoxib acts to:
Selectively inhibits COX-2
Function of prostaglandin F2alpha
PGF2alpha: produced by most tissues, vasoconstriction and bronchoconstriction, contraction of smooth muscle, stimulates uterine contractions
Function of thromboxane A2
Produced by COX-1 primarily in platelets.
-Promotes platelet aggregation
-Vasoconstriction and bronchoconstriction
-Mobilizes intracellular calcium
-Contraction of smooth muscle
PGE2
Mediator of inflammation; Released from activated macrophages. Cause local vasodilation (redness); pain; fever (signs of inflammatory response)
-Protects gastric mucosa
Which two molecules induces labor in pregnant uterus?
PGE2 and PGF2-alpha
Cortisol inhibits which molecule?
Phospholipase A2: release of arachidonic acid from membrane phospholipids
and also
COX-2: anti-inflammatory agent
The cysteinyl leuotrienes
LTC4, LTD4, LTE4
Major site of synthesis for PGE2
Activated macrophages
Major site of synthesis for PGF2-alpha
Uterine tissues
Major site of synthesis for Prostacyclin
Endothelium of blood vessels
Major site of synthesis for platelets:
Thromboxane A2
Major site of synthesis for mast cells:
Cysteinyl leukotrienes: LTC4: LTD4: LTE4
Major mediator of inflammation; Vasodilation (redness); Pain; Swelling
PGE2
Stimulates uterine contractions
PGF2-alpha
Inhibits platelet aggregation; Increases formation of cAMP in platelets; Vasodilation
Prostacyclin
Promotes platelet aggregation; Vasoconstriction; decreases formation of cAMP in platelets; mobilizes intracellular Calcium
Thromboxane A2
Bronchoconstriction; Increases vascular permeability; Component of slow-reacting substance of anaphylaxis (SRS-A)
Cysteinyl leukotrienes
