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135 Cards in this Set
- Front
- Back
What are 4 functions of lipids?
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1 Major source of energy (9kcal/g)
2 Hydrophobic barrier allowing the partitioning of subcellular structures 3 Regulators and cofactors (fat-soluble vitamins) 4 Precursors to prostaglandins and steroid hormones |
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What type of lipids are used in energy production?
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Fatty acids
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Lipids are stored in adipose tissue as what?
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Triglycerides (glycerol esters)
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Lipids are prackaged in lipoproteins in order to do what?
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To be transported to the site of their metabolism and use.
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T/F
Deficiency or imbalance of lipid metabolism leads to obesity and atherosclerosis. |
True!
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What are dietary lipids comprised of?
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Triglycerides (esterified fatty acids)
Unesterified fatty acids (free fatty acids) Cholesterol Cholesteryl esters Phospholipids |
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What emulsifies dietary lipids and what degrades dietary lipids during digestion?
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Bile salts emulsify, and pancreatic enzymes degrade.
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Triacylglycerols containing FAs with short- or medium-length chains are digested by what types of enzymes?
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Lingual and gastric lipases
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Lingual and gastric lipases are (base/acid)-stable enzymes.
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Acid-stable
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What are important in lipid digestion in both neonates (milk fat) and cystic fibrosis (absence of pancreatic lipase)?
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Lingual and gastric lipases
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What needs to happen in order for triacylglycerols containing long-chain FAs to be digested?
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They must be emulsified, which is facilitated by bile salts and peristalsis
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What is the purpose of emulsification?
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It increases the surface area of lipid droplets for better digestion.
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What are bile salts produced from, and where?
Where are they stored? |
From cholesterol in the liver
Gall bladder |
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What is the purpose of the gut hormone cholecystokinin?
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It stimulates the release of bile salts from the gallbladder.
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How are bile salts recycled? A diet rich in what will decrease the amount of recycled bile?
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Bile salts are taken back to the liver via enterohepatic circulation.
A diet rich in fiber decreases the amount of recycled bile. |
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For triacylglycerol absorption, pancreatic lipase, esterase removes FAs resulting in what?
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2-monoacylglycerol and free fatty acids
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What pancreatic enzyme binds to lipase (pancreatic or intestinal) for better lipid digestion?
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Colipase
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What does the anti-obesity drug Orlistat inhibit? How does this cause weight loss?
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Orlistat inhibits lipases → undigested lipids → fat malabsorption → weight loss
Orlistat does NOT inhibit absorption |
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What enzyme hydrolyzes cholesterol esters into free cholesterol and free fatty acids?
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Cholesterol ester hydrolase (cholesterol esterase)
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The activity of cholesterol esterase is (decreased/increased) by bile salts.
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Increased
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What catalyzes the hydrolytic removal of FA from carbon 2 of a phospholipid?
What are the products? |
Phospholipase A2
The product is a FFA + lysophospholipid |
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In phospholipid degradation,
What enzyme removes FA on carbon 1 from the lysophospholipid? The remaining glycerylphosphoryl base may be... |
Lysophospholipase
Excreted or absorbed |
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What are the 4 products of dietary lipid degradation?
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Free FAs
Free cholesterol 2-monoacyglycerol glycerylphosphoryl |
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What do the products of lipid degradation form with bile salts?
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Mixed micelles with bile salts for absorption
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T/F
Mixed micelles are organized with the amphiphilic groups of the lipids on the inside and are fat soluble. |
False!
Mixed micelles are organized with the amphiphilic groups of the lipids on the OUTSIDE and are WATER soluble. They are water soluble, facilitating the transport of the digested dietary lipids. |
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How are short- and medium-chain FAs absorbed by intestinal mucosal cells (enterocytes) compared to long-chain FAs?
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Short and medium chain length FAs are absorbed without mixed micelle structure, whereas long-chain FA's must be in micelle form to be absorbed by the brush border cells through the membrane.
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Why should individuals suffering from lipid malabsorption consider the intake of short- and medium-chain FAs only?
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Because short and medium chain length FAs can be absorbed by enterocytes without mixed micelle structure. (absorbed more easily)
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What are a couple possible causes of lipid malabsorption?
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Cystic fibrosis and malfunction of exocrine cells of the liver, pancreas, or gallbladder.
Shortened bowel |
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Why does steatorrhea result from lipid malabsorption?
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Dietary lipids and fat soluble vitamins are being eliminated in the feces-->chronic diarrhea & weight loss
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After absorption, lipids migrate to what structure in enterocytes?
Why, what occurs at this structure? |
Endoplasmic reticulum (ER)
The ER is the site of biosynthesis of complex lipids. |
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What needs to happen before FAs can be used in the synthesis of triacylglycerols or the esterification of cholesterol?
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FAs are first activated by acetylation by fatty acyl CoA synthetase (thiokinase)
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What can be converted back to triacylglycerols by triacylglycerol synthase?
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2-monoacylglycerol
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What can be reacylated back to phospholipids by acyltransferase?
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Lysophospholipids
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What enzyme converts cholesterol to a cholesterol ester?
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CoA:cholesterolacyltransferase
(Acyltransferase) |
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What happens to short and medium chain length FAs after being released into the blood?
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They are solubilized and transported to the liver by albumin.
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Because they are hydrophobic molecules, lipids need to be packaged for transport in the aqueous blood medium. What do they become packaged in?
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Dietary lipids are enclosed in a capsule named chylomicrons.
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What are chylomicrons made up of?
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Triacylglycerols 82% (most abundant component*)
Phospholipids 7% Cholesterol and cholesterol esters 9% |
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What are chylomicrons packaged in?
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Apolipoprotein B-48
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What facilitates the binding of lipids to Apo B-48?
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Microsomal triglyceride transfer protein (MTP)
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*Abetalipoproteinemia, a disease characterized by absence of chylomicrons in plasma, is caused by an absence of what?
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Microsomal triglyceride transfer protein (MTP)
*abetalipoproteinemia is autosomal recessive & results in severe neuropathy |
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As chylomicrons move through the blood and lymph, what do they acquire from HDL?
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ApoC and apoE
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How do chylomicrons get from enterocytes to the blood?
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Chylomicrons are released by exocytosis from enterocytes to the blood via the lymphatic system.
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? ApoCII acts as an (inhibitor/activator) of lipoprotein lipase (LPL).
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Activator
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What enzyme allows triglycerides contained in chylomicrons to be degraded into FAs and glycerol and released in the capillaries?
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Lipoprotein lipase (LPL)
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Triglycerides contained in chylomicrons are released in the capillaries of what tissues?
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Muscle (particularly cardiac)
Adipose tissues (isoenzyme with the highest Km) Lactating mammary gland Lung Kidney Liver |
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To be transported in the blood, what are FFAs bound to?
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Albumin
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In all cells containing mitochondria, what can happen to FFAs?
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They can be oxidized to synthesize ATP.
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In adipose, what happens to FFAs?
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They are esterified to triglycerides for storage.
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?Is ApoCII degraded?
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No
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*What secretes lipoprotein lipase (LPL)?
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Adipocytes, and
Muscle cells |
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*LPL of the adipose tissue has (low/high) Km.
LPL of the heart muscle has (low/high) Km. |
High
Low |
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*T/F
LPL becomes associated with the luminal surface of endothelial cells of capillary beds of peripheral tissues. |
True!
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*a) Why does low insulin result in an accumulation of lipoproteins?
b) Does insulin inhibit or stimulate hormone-sensitive lipase in adipose tissues? c) What happens in diabetes mellitus? |
a) Because LPL synthesis is stimulated by insulin. If there is low insulin there will be less LPL to release triglycerides into capillaries.
b) Inhibits c) Diabetes mellitus: low or absent insulin → low LPL and high hormone-sensitive lipase → hypertriacylglycerolemia |
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*Familial lipoprotein lipase
(type I hyperlipoproteinemia) deficiency results in massive what? What inheritance pattern is it? |
Chylomicronemia
Autosomal recessive |
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*Glycerol that is released by hydrolysis of TG by LPL may be activated through phosphorylation and used by the liver to form what?
This can then be used for what in the... a) fed state b) fasting state |
Glycerol 3-phosphate
a) TG synthesis in liver b) Gluconeogenesis |
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What are the chylomicron remnants after hydrolysis of TGs?
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Cholesteryl esters
Phospholipids Apolipoproteins, and Few triacylglycerol |
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Chylomicron remnants are endocytosed by the ______ with receptors for hydrolysis.
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Liver
This remnant binds to receptors on hepatocytes: LDL receptor-related protein (LRP) |
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What part of the chylomicron remnant is recognized by membrane receptors on hepatocytes?
What are the degraded products that will be reused by the cell? |
ApoE
LRP → endocytosis → degradation by lysosomal enzymes → products reused by the cell Fatty acids Amino acids Glycerol Cholesterol |
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Compromised removal of chylomicron remnants by the liver results in their accumulation in plasma seen in what disorders?
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Type III hyperlipoproteinemia/ dysbetalipoproteinemia
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Chylomicrons are synthesized in a)______________ cells, secreted into the lymph, pass into the blood where they become mature. On capillary wall in adipose tissue and muscle, lipoprotein lipase (LPL) activated by b)_____ digests the TG of chylomicrons to c)_____ and d)________. (c) are oxidized in e)_________ or stored in adipose cells as TG. The remnants of the chylomicrons are taken up by the f)_______ by receptor-mediated endocytosis. Lysosomal enzymes within the hepatocyte digest the remnants, releasing the product into the cytosol.
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a) intestinal epithelial
b) ApoCII c) FA d) Glycerol e) muscle f) liver |
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Which lipoproteins contain predominantly hepatic TG?
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VLDL
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What are VLDLs synthesized from?
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Chylomicrons remnant (Chylomicrons that were not hydrolyzed in the peripheral tissue)
Dietary carbohydrates (major source of carbon): Glucose → Acetyl CoA → Fatty acids Glucose → Dihydroxyacetone phosphate → glycerol Fatty acids + Glycerol → TG |
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What can cause carbohydrate induced hypertriglyceridemia?
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High carbohydrates intake
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Where are VLDLs assembled?
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Liver
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What facilitates the binding of TG to apoB100?
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Microsomal triglyceride transfer protein (MTP)
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What lipoproteins are high 4 to 6 hours after a meal?
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VLDL
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T/F
In healthy individuals, VLDLs represent about 50% of the total circulating lipoproteins. |
False!
In healthy individuals, they represent only 10% to 15% of the total circulating lipoproteins. |
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a)___________ is the synthesis of TGs from glucose. In humans, the synthesis of FAs from glucose occurs in the b)________. FAs are converted to TGs, packaged in c)________, and secreted into the blood.
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a) Lipogenesis
b) liver c) VLDL |
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What are the components of VLDLs?
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52% triglycerides (TG)
22% cholesterol 18% phospholipids 8% apoproteins |
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What is the major apoprotein associated with VLDL?
What other 2 do they contain? |
Apo B100
They also contain apoC and apoE transferred from HDL. |
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What is the function of VLDLs?
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They transport triacylglycerol from the liver to the peripheral tissue.
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When does fatty liver/hepatic steatosis occur?
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When triglycerides in the liver are higher than those secreted as VLDL.
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After hydrolysis of VLDLs (by LPL), what is transferred back to HDL?
What happens to their remnant (with less TG and more cholesterol)? |
apoC and apoE
Their remnant can either be internalized by the liver for further hydrolysis or converted into IDL, then LDL. |
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The conversion from IDL to LDL is facilitated by the action of what enzyme?
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Hepatic triglyceride lipase (HTGL)
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LPL causes VLDLs to lose triglycerides, which results in a (decrease/increase) in size and (decrease/increase) in density.
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Decrease, increase
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Triglycerides from VLDLs are exchanged for ___________ from HDLs.
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Cholesteryl esters (CE)
Transfer of CE catalyzed by: Cholesteryl ester transfer protein |
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Why are TGs exchanged for cholesterol esters between VLDL and HDL?
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In order to esterify cholesterol collected by HDL.
(esterification reduces cholesterol mobility, allowing HDL to sequester it) |
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Fate of VLDL:
TG of VLDL produced in the liver is digested by the LPL present on the lining cells of capillaries in a)_____________. FAs are released and either oxidized or stored in tissues as TG. Glycerol is used by the liver and other tissues that contain b)_____________. |
a) adipose and muscle tissue
b) glycerol kinase |
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Fate of VLDL:
VLDL triacylglycerol (TG) is degraded by LPL, forming a)______. (a) can either be endocytosed by the liver through a receptor-mediated process or further digested, mainly by b)____________ to form LDL. LDL may be endocytosed by receptor-mediated processes in the liver or in peripheral cells. LDL also may be oxidized and taken up by “scavenger” receptors on c)___________. The scavenger pathway plays a role in d)_____________. |
a) IDL
b) hepatic triacylglycerol lipase (HTGL) c) macrophages d) atherosclerosis |
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Low-density lipoproteins are formed primarily from _______ catabolism.
They can be directly synthesized by the ______ |
VLDL
VLDL-->IDL-->LDL DIRECTLY synthesized by the liver |
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LDLs carry what to peripheral tissues before reaching the liver?
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Cholesteryl esters
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T/F
In a healthy person, LDLs constitute 2/3 of plasma cholesterol. |
True!
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What are the components of LDLs?
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47% cholesterol
23% phospholipids 21% apoprotein (only B100) 9% triglycerides |
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What lipoproteins transport about 60% of the total cholesterol (fasting plasma)?
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LDLs
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2/3 of the cholesterol carried by LDLs is esterified with what?
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Long-chain FAs (linoleic acid)
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Where does hydrolysis of cholesteryl esters take place?
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Liver
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Cholesteryl ester synthesis takes place mainly where?
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Plasma
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Liver synthesizes ____% of the daily cholesterol.
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70%
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Why are LDL taken up by hepatocyte?
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To clear LDL from circulation and regulate cholesterol synthesis
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In the liver, LDL are degraded by lysosomal enzymes into what 2 things?
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Free cholesterol
Amino acids |
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The increase of [free cholesterol] in the liver causes what 3 things to be decreased/increased?
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1. Decreases the activity of HMG CoA reductase
2. Increases the activity of acyl CoA cholesterol acyl transferase (ACAT) 3. Decreases LDL receptor production |
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HMG CoA reductase is (inhibited/stimulated) by high cholesterol.
(mechanism of maintaining cholesterol homeostasis) |
Inhibited. This causes a decrease of cholesterol de novo synthesis.
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How can the body limit entry of LDL cholesterol into liver cells?
(mechanism of maintaining cholesterol homeostasis) |
By reducing synthesis of new LDL receptors
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Cholesterol is esterified by acyl CoA:cholesterol acyltransferase (ACAT). ACAT is activated by (low/high) levels of intracellular cholesterol.
(mechanism of maintaining cholesterol homeostasis) |
High
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What deficiency is Type II hyperlipidemia or familial hypercholesterolemia caused by?
What does this cause? |
Deficiency in functional LDL receptors
Premature atherosclerosis |
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What hormone stimulates the binding of LDL to its receptor?
Therefore, what can cause hypercholesterolemia (in relation to this hormone)? |
Thyroid hormone, T3
Hypothyroidism (Hypercholesterolemia secondary to hypothyroidism) |
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A deficiency in enzymes for cholesteryl esters hydrolysis is known as what?
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Wolman disease
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Deficiency in releasing cholesterol from lysosomes is known as what?
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Niemann-Pick disease, type C
*Do not confuse with Niemann-Pick or NP type A 1:80 in Ashkenazi Jews |
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What are the components of HDL?
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50% apoproteins
28% phospholipids 19% cholesterol 3% triglycerides |
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What is the major apoprotein in HDL?
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apoA (I and II)
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HDL exchanges what apoproteins with chylomicrons, LDL, and VLDL?
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apoC and apoE
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Where is HDL assembled?
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Liver and intestine
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High-density lipoproteins transport what from tissues to the liver?
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Esterified cholesterol
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What is esterified by lecithin:cholesterol acyltransferase (LCAT) on HDL?
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Free cholesterol
Cholesterol + FA → cholesterol ester |
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Where do the FAs come from that are needed to esterify cholesterol using LCAT on HDL?
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The FAs needed for esterification are taken from chylomicrons, LDL and VLDL by HDL in exchange of apoC and apoE.
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What is the preferred substrate for human LCAT (plasmatic enzyme)?
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HDL
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What is esterified cholesterol transferred to from HDL, partly in exhcange for TG?
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LDL and VLDL
The transfer is catalyzed by cholesterol ester transfer protein (CETP) |
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Familial deficiency of HDL results in what disease?
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Tangier disease, aka familial high-density lipoprotein disease. This is caused by a lack of apoAI synthesis.
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Oxidation of LDL particles leads to their uptake by microphages and therefore formation of foam cells. This process results in what?
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Atherosclerosis
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What are 3 possible causes of hypercholesterolemia?
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Inability to synthesize HDL, hypothyroidism and lack of LDL receptors.
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T/F
LDL can be DIRECTLY synthesized from the liver if there is a need for cholesterol right then. |
True!
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Which lipoprotein has the highest cholesterol content? The lowest?
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Highest - LDL
Lowest - Chylomicrons |
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Which lipoprotein has the highest TAG content? The lowest?
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Highest - Chylomicrons
Lowest - HDL |
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Match HDL, LDL, VLDL, and chylomicron to the appropriate description.
a) Synthesized from VLDL and delivers cholesterol to the peripheral tissues b) Synthesized by the liver and delivers de novo TAG to peripheral tissues c) Synthesized by the liver and intestines and delivers esterfied cholesterol to the liver for elimination d) Synthesized by the intestine and delivers dietary TAG to peripheral tissues |
a) LDL
b) VLDL c) HDL d) Chylomicron |
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What are the 3 possible functions of apoproteins?
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Recognition of cellular receptors
Lipid enzyme activators, or Lipid enzyme inhibitors |
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Which apoprotein activates LCAT and is a structural component of HDL?
Where is it found? What lipoproteins carries it? |
apoAI
intestine & liver HDL (chylomicron) |
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Which apoprotein is a ligand for the LDL receptor?
Where is it found? What lipoproteins carries it? |
apoB100
Liver VLDL, IDL, LDL |
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Which apoprotein is a cofactor activator of LPL?
Where is it found? What lipoproteins carries it? |
apoCII
Liver Chylomicrons, VLDL, IDL, HDL |
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Which apoprotein is an inhibitor of LPL and may inhibit hepatic uptake of chylomicrons and VLDL remnants?
Where is it found? What lipoproteins carries it? |
apoCIII
Liver Chylomicrons, VLDL, IDL, HDL |
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Which apoprotein is a ligand for binding of several lipoproteins to the LDL receptor, to the LDL receptor-related protein (LRP) and possibly to a separate apoE receptor?
Where is it found? What lipoproteins carries it? |
apoE
Liver Chylomicron remnants, VLDL, IDL, HDL |
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In a centrifuge, what would be the order of lipoproteins from bottom to top?
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Albumin-fatty acid complex > HDL > LDL = IDL > VLDL > Chylomicrons
*chylomicrons are the "milky" part at top |
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In electrophoresis, what would be the order of lipoproteins from closest to furthest?
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Chylomicrons < VLDL < IDL <LDL < HDL
(origin) (pre-beta) (beta) (alpha) (--> increasing percentage) |
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What can lipoproteins be separated by?
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Ultracentrifugation
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T/F
Lipid and lipoprotein measurements are used to evaluate cardiovascular risk |
True!
|
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The risks of what disease are directly correlated with fasting (12hrs) levels of :
Total cholesterol (nonfasting for screening) LDL-cholesterol HDL-cholesterol Total-cholesterol-to-HDL ratio |
Coronary heart disease (CHD)
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What can be measured with more accuracy independently than with the Friedewarld calculation and does not require fasting?
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LDL-C can be evaluated independently from the other lipoproteins with “LDL direct."
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What's the only thing you can do to increase HDL?
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Exercise!
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Combined hyperlipoproteinemia is characterized by elevated levels of what?
|
Elevated cholesterol
Elevated triglycerides, or Elevation of both (C and TG) Low HDL |
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Familial dysbetalipoproteinemia or Type III hyperlipoproteinemia results in accumulation of what?
What is this caused by? |
Accumulation of cholesterol-rich VLDL and chylomicron remnants.
Caused by defective catabolism of the above particles resulting from deficiency in apoprotein E. (Apo E2/E homozygosity or, very rarely, apo E deficiency) |
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Describe the homozygous vs heterozygous forms of familial hypercholesterolemia.
The heterozygous form can be treated with what? What can help the homozygous form? |
Homozygote (1:1000,000)
[Cholesterol] 800 to 1000 mg/dL First heart attack in teenage years Heterozygote (more frequent, 1:500) [Cholesterol] 300 to 600 mg/dL Heart attack between 20s and 50s FH tuberous xanthomas under the skin and in vessels of the eye Only heterozygotes can be helped with statins. Because statins help enhance the gene for LDL receptor synthesis, which homozygotes don't have a copy of. Homozygotes can benefit from LDL pheresis. |
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Which form of dyslipidemia is caused by overproduction of apoB100
and has a plasma lipid pattern of hypercholesterolemia mixed hyperlipidemia (IIa or IIb)? |
Familial combined hyperlipidemia
|
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What are some positive cardiovascular risk factors?
|
Age (years)
Male ≥ 45 Female ≥ 55 or premature menopause without estrogen replacement therapy Family history of premature CHD Current cigarette smoking Hypertension Obesity Sedentary lifestyle Diabetes mellitus Low HDL Cholesterol, < 350 mg/L |
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What is a negative cardiovascular risk factor?
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High HDL cholesterol, ≥ 600 mg/L
|
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Diabetes melitus is a result of low or absent insulin, leading to (low/high) LPL and (low/high) concentration of hormone-senstive lipase, resulting in hypertriacylglycerolemia.
|
low LPL
high concentration of hormone-sensitive lipase |
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*Familial LCAT deficiency leads to complete absense of LCAT activity resulting in esterification anomalies of both HDL & LDL. It causes a typical triad which includes ______________
|
Triad:
1. Diffused corneal opacities 2. Target cell hemolytic anemia 3. proteinuria w/ renal failure |