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Questions and Answers
What is the primary role of Chylomicron remnants after they are formed?
What is the primary role of Chylomicron remnants after they are formed?
Which factor is essential for the activity of lipase in the presence of lipids?
Which factor is essential for the activity of lipase in the presence of lipids?
What consequence is associated with fat malabsorption?
What consequence is associated with fat malabsorption?
What do VLDLs primarily transport in the body?
What do VLDLs primarily transport in the body?
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How do Chylomicron remnants interact with liver cells?
How do Chylomicron remnants interact with liver cells?
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What is the primary function of ApoB-100 in VLDL?
What is the primary function of ApoB-100 in VLDL?
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What happens to VLDL after it loses triglycerides?
What happens to VLDL after it loses triglycerides?
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How do IDL particles enter liver hepatocytes?
How do IDL particles enter liver hepatocytes?
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What role does the LDL receptor play in cholesterol metabolism?
What role does the LDL receptor play in cholesterol metabolism?
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What is the consequence of high LDL levels in the body?
What is the consequence of high LDL levels in the body?
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What causes Abetalipoproteinemia?
What causes Abetalipoproteinemia?
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Where does RNA editing of the ApoB-100 gene occur?
Where does RNA editing of the ApoB-100 gene occur?
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Which apoproteins are transferred to nascent chylomicrons to form mature chylomicrons?
Which apoproteins are transferred to nascent chylomicrons to form mature chylomicrons?
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What is the function of LPL in relation to chylomicrons?
What is the function of LPL in relation to chylomicrons?
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What stimulates LPL synthesis in adipose tissue?
What stimulates LPL synthesis in adipose tissue?
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What is released when LPL hydrolyzes triglycerides?
What is released when LPL hydrolyzes triglycerides?
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What happens to the remaining chylomicron after triglyceride hydrolysis?
What happens to the remaining chylomicron after triglyceride hydrolysis?
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What is the role of ApoCII in the process of LPL activity?
What is the role of ApoCII in the process of LPL activity?
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What is the distinguishing feature of Lp(a)?
What is the distinguishing feature of Lp(a)?
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Which factor is primarily responsible for the levels of Lp(a) in individuals?
Which factor is primarily responsible for the levels of Lp(a) in individuals?
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How does elevated Lp(a) potentially contribute to heart attack risk?
How does elevated Lp(a) potentially contribute to heart attack risk?
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What effect does Niacin (vit.B3) have on Lp(a) levels?
What effect does Niacin (vit.B3) have on Lp(a) levels?
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What is currently known about the physiological function of Lp(a)?
What is currently known about the physiological function of Lp(a)?
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Which enzyme is responsible for the re-esterification of free cholesterol inside the cell?
Which enzyme is responsible for the re-esterification of free cholesterol inside the cell?
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What occurs as a result of high intracellular cholesterol levels in relation to LDL receptors?
What occurs as a result of high intracellular cholesterol levels in relation to LDL receptors?
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What disease is characterized by an inability to release cholesterol from lysosomes?
What disease is characterized by an inability to release cholesterol from lysosomes?
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What shape is the nascent HDL particle primarily when synthesized?
What shape is the nascent HDL particle primarily when synthesized?
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Which protein is essential for the transfer of cholesterol from HDL to VLDL?
Which protein is essential for the transfer of cholesterol from HDL to VLDL?
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What is the role of ABCA1 in cholesterol transport?
What is the role of ABCA1 in cholesterol transport?
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Which HDL subtype is considered atherogenic and protective?
Which HDL subtype is considered atherogenic and protective?
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How does HDL differ from LDL in terms of endocytosis?
How does HDL differ from LDL in terms of endocytosis?
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What is Lipoprotein(a) [Lp(a)] primarily similar to?
What is Lipoprotein(a) [Lp(a)] primarily similar to?
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Which enzyme is activated by Apo A1 to facilitate cholesterol esterification in HDL?
Which enzyme is activated by Apo A1 to facilitate cholesterol esterification in HDL?
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Study Notes
Abetalipoproteinemia
- Defect in Microsomal Triglyceride Transfer Protein (MTP) causes Abetalipoproteinemia
- MTP is critical for the assembly and secretion of very-low-density lipoproteins (VLDL) and chylomicrons
Chylomicron Transport
- Chylomicrons are synthesized and secreted into the lymphatic system by intestinal epithelial cells
- Chylomicrons enter the bloodstream via the thoracic duct
- Chylomicrons transport dietary lipids in the blood
- ApoB-48 is the structural apoprotein of chylomicrons
- ApoB-48 is produced by RNA editing of the ApoB-100 gene, which creates a STOP codon in the intestine
- Chylomicron maturation involves the transfer of apoproteins from HDLs to nascent chylomicrons, forming mature chylomicrons
- ApoCII stimulates lipoprotein lipase (LPL)
- ApoE is recognized by receptors
- LPL hydrolyzes the triglycerides (TGs) of chylomicrons, releasing fatty acids and glycerol
- LPL is found on the basement membrane of capillary endothelium
- LPL is particularly abundant in adipose tissues, muscle, and mammary gland
- Insulin stimulates LPL synthesis in adipose tissues
- Fatty acids can be used as energy or stored
- Glycerol is used by the liver for lipid synthesis, glycolysis, or gluconeogenesis
- Chylomicron remnants are taken up by the liver
Clinical Issues related to Chylomicrons
- Fat malabsorption can occur due to pancreatic failure, lack of bile salts, or intestinal diseases
- Pancreatic failure leads to a deficiency in lipase and colipase, which are essential for lipid digestion
- Lack of bile salts, caused by bile duct blockage, prevents the formation of micelles, disrupting lipid absorption
- Malabsorption causes steatorrhea (bulky fatty stools)
- Fat-soluble vitamin absorption (D, E, A, K) is impaired due to chylomicron dysfunction
Colipase
- Anchors lipase to the lipid-aqueous interface
- Restores lipase activity in the presence of inhibitory substances like bile salts
VLDL, IDL, and LDL
- VLDL are synthesized in the liver from endogenous lipids, mainly excess carbohydrates
- VLDL are secreted into the hepatic veins as nascent VLDL
- VLDL maturation involves accepting apoE and apoCII from HDL to become mature VLDL
- VLDL transport lipids to peripheral tissues like muscle (used as energy) and adipose tissue (storage)
- ApoB-100 is the structural apoprotein of VLDL
- Microsomal triacylglycerol transfer proteins (MTP) load lipids with ApoB-100 to form VLDL
- LPL digests the TGs of VLDL
- VLDL becomes VLDL remnant (IDL) after losing TG
- IDL can be taken up by liver hepatocytes via the apoE receptor
- IDL can be further metabolized into LDL
- LDL is rich in cholesterol
- LDL is taken up by liver or peripheral tissues through the LDL receptor
- LDL receptor binds to apoB-100
- High LDL levels can saturate liver uptake, leading to excess and oxidized LDL being taken up by macrophages, forming foam cells and plaque, contributing to atherosclerosis
- The LDL receptor is found in many tissues and is an integral protein with six regions
- Negatively charged amino terminal domain interacts with apoB-100 of LDL
- Also binds to apoE
- Cellular uptake and degradation of LDL involve endocytosis and fusion with lysosomes
- The LDL receptor returns to the membrane after LDL is released
- Cholesterol can be re-esterified by Acyl CoA:Cholesterol AcylTransferase (ACAT)
- Esterification prevents cholesterol from entering the cytoplasmic membrane
- Usually esterified to oleate (18:1) or palmitolate (16:1)
- LDL cholesterol ester usually linoleate (18:2)
- LDL receptor synthesis is down-regulated by cholesterol
- Involves SREBP (Sterol Regulatory Element Binding Proteins)
- Niemann-Pick type C disease impairs cholesterol release from lysosomes, causing cholesterol buildup and cell death
HDL
- HDL is synthesized in the liver and intestine
- Nascent HDL particles are disk-shaped, containing primarily phospholipids
- HDL contains/transfers several apoproteins, including ApoA, ApoE, and ApoCII
- Mature HDL, also known as HDL3, is globular-shaped and accumulates cholesterol
- High cholesterol HDL, also known as HDL2, is atherogenic protective
- HDL plays a major role in reverse cholesterol transport
- HDL picks up free cholesterol from extrahepatic tissues and transfers them to the liver or VLDL
- Cells utilize reverse cholesterol transport to eliminate excess cholesterol
- ABC1 (ATP-binding cassette transporter) moves cholesterol from the inner leaflet of the plasma membrane to the outer leaflet
- Tangier disease is caused by ABCA1 deficiency, leading to reduced HDL
- Cholesterol is transferred to HDL
- ABC1 (ATP-binding cassette transporter) moves cholesterol from the inner leaflet of the plasma membrane to the outer leaflet
- HDL picks up cholesterol from extrahepatic cells with the help of two enzymes:
- LCAT (Lecithin: Cholesterol Acyl Transferase):
- Activated by ApoA1
- Synthesizes cholesterol ester (CE)
- Fatty acids come from phosphatidylcholine (lecithin)
- Traps cholesterol in HDL
- CETP (Cholesterol Ester Transfer Protein):
- Transfers cholesterol ester to VLDL in exchange for triglyceride and phospholipid
- LCAT (Lecithin: Cholesterol Acyl Transferase):
- HDLs bind to the scavenger receptor (SR-B1) on hepatocytes:
- Cholesterol and Cholesterol ester are transferred into the liver cell
- There is no endocytosis, unlike the LDL receptor
- HDL dissociates and returns to circulation
- SR-B1 can be up-regulated by cells requiring cholesterol
Summary of Plasma Lipoproteins
- Chylomicrons: Synthesized by intestinal epithelial cells from dietary fat, carries triacylglycerol in blood
- VLDL: Produced in the liver from mainly dietary carbohydrates, carries triacylglycerol in blood
- IDL: Produced in the blood as a remnant of VLDL, endocytosed by liver, or converted to LDL
- LDL: Produced in blood as a remnant of IDL, contains a high concentration of cholesterol and cholesterol ester, endocytosed by the liver and peripheral tissues
- HDL: Produced in the liver and intestine, exchanges proteins and lipids with other lipoproteins, functions in reverse cholesterol transport
Lp(a)
- Lipoprotein(a) or Lp(a) is similar to LDL, but it contains apolipoprotein(a) (apo(a)) covalently linked to apoB-100
- Apo(a) is structurally similar to plasminogen
- High levels of Lp(a) are associated with increased risk of coronary heart disease
- Mostly genetically controlled
- High dietary trans fats can increase Lp(a) levels
- The physiological function of Lp(a) is unclear, but one hypothesis is that it slows down the breakdown of blood clots by competing with plasminogen for binding to fibrin
- Niacin (vitamin B3) reduces Lp(a), LDL-cholesterol, and triglycerides, and raises HDL
Key Concepts
- Chylomicrons, VLDL, IDL, LDL, HDL, Lp(a), apoproteins
- MTP (Microsomal Triglyceride Transfer Protein)
- Lipoprotein lipase (LPL)
- Reverse cholesterol transport
Clinical Correlations
- Abetalipoproteinemia: Impaired lipoprotein assembly and secretion due to MTP deficiency
- Fat Malabsorption: Causes steatorrhea (fatty stools)
- Niemann-Pick type C disease: Impaired cholesterol release from lysosomes, leading to cholesterol accumulation and cell death
- Tangier disease: Reduced HDL due to ABCA1 deficiency
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Description
This quiz covers the important concepts related to Abetalipoproteinemia and the transport of chylomicrons. You will explore the role of Microsomal Triglyceride Transfer Protein (MTP) in lipid metabolism, the significance of ApoB-48 in chylomicron synthesis, and the mechanisms of chylomicron maturation and function. Test your understanding of these critical biological processes.
