Study sets, textbooks, questions
Upgrade to remove ads
Lipid transport and storage
Terms in this set (58)
How are lipids transported in the blood?
What are the different classes of lipoproteins?
Very-low-density lipoprotein (VLDL)
Intermediate-density lipoprotein (IDL)
Low-density lipoprotein (LDL)
High-density lipoprotein (HDL)
What are the different ways lipoproteins can be transported?
Exogenous (diet) lipid transport
Endogenous lipid transport
reverse cholesterol transport
Describe the structure of a lipoprotein
A hydrophobic, nonpolar "neutral" lipid (TAG and cholesterol ester) reside in the core. Which is surrounded by a monolayer of amphipathic phospholipids and free cholesterol which encapsulates the neutral lipid from the aqueous solution.
describe the density of lipoproteins.
Lipoproteins with high proportions of lipid have a lower density.
The largest and least dense lipoprotein is chylomicron
The smallest and densest lipoprotein is HDL
WHat is the main function of lipoproteins?
transport lipids in the blood
What is the exogenous lipid transportation system?
This system involves chylomicrons, and refers to transport of TAG from intestine to peripheral tissue for storage or energy utilization.
This system operates only after a fat-containing meal.
Are chylomicrons always present in the bloodstream?
No, they disappear after all dietary TAG are delivered to tissues.
What is the endogenous lipid transport system?
This system involves VLDL, IDL, and LDL. It refers to the transport of TAG from the liver to peripheral tissues for storage or energy utilization.
This system operates continuously to maintain proper balance of fatty acid that accumulate in the liver during normal metabolism.
What is reverse cholesterol transport system?
This system involves HDL. HDL picks up excess cholesterol from peripheral tissues and delivers it to the liver to be excreted.
What prevents excessive increase in blood TAG levels?
Chylomicrons only enter at a slow pace.
They can continue to enter bloodstream upto 14hrs after large fat intake.
When does blood TAG concentration peak?
30min - 3hrs after meal.
What is unique about lipoprotein that express apoE?
they can bind to LDL receptor and be cleared of circulation. (undergo degradation from hepatocytes)
What is the key enzyme that hydrolyze TAG and phospholipids of chylomicron "remnants" within the hepatocyte?
Upon ingesting a high fat meal, what is the likely destination of chylomicrons?
In the fed state which metabolic pathway is favored for TAG, which enzyme and hormone influences this?
Fatty acid synthesis.
Insulin increases the uptake of free fatty acids and monoacylglycerols in adipocytes by stimulating lipoprotein lipase.
Insulin has two lipogenic actions in adipocytes, what are they?
1.) Insulin increases the uptake of free fatty acids and monoacylglycerols in adipocytes by stimulating lipoprotein lipase.
2.) Insulin inhibits hormone-sensitive lipase, which hydrolyzes TAG.
How can LDL accumulate in the blood?
It depends on receptor expression. If receptors are few LDL accumulates.
The liver has a limited capacity to store TAG, what does this mean?
The liver continuously ships out VLDL to lower TAG concentration.
Which precursors can the liver use to synthesize new TAG?
"preformed" lipids (chylomicron "remnants, LDL, HDL)
Cholesterol and cholesterol esters from chylomicron "remnants" may be used in which ways by the liver?
1.) converted into bile salts
2.) secreted directly into the bile as free cholesterol
3.) incorporated into cellular membrane as free cholesterol
4.) incorporated into VLDL and released into blood
What have clinical studies determined about the size of LDL?
small dense LDL is more atherogenic than large LDL.
Which two apoproteins can attach to LDL receptor?
apoB-100 & apoE
Which dietary factor influence the number of LDL receptors?
SFA and trans decrease receptors
soluble fiber and phytosterols increase receptors
How does obesity influence LDL receptors?
Obese individuals are less responsive to dietary treatment.
WHat happens in people with a mutation of the protein PCSK9?
They have lower levels of LDL (and CVD risk)
Where does the conversion of cholesterol to regulatory hormones take place?
What are the different cholesterol products?
In the liver.
sex hormones, bile acids, Vit. D
What is the main apoprotein for HDL?
In what way does HDL decrease the risk of CVD?
nascent HDL accepts cholesterol from macrophages within cardiovascular tissue, this reduces the amount of deposited cholesterol on the endothelium.
What receptor does mature HDL respond to?
What are large particles of HDL associated with?
Decreased risk of CVD. large HDL is the final mature stage of HDL after it has gather cholesterol. So cholesterol has been removed.
What are small particles of HDL associated with?
Increased risk of CVD.
Explain exogenous lipid transport
Chylomicrons (containing TAG, apoB-48 & apoA-1) released from the lymphatic system enter into the bloodstream. Here Chylomicrons acquire more apolipoproteins, apoE & apoC-2, from HDL as they interact. The circulating chylomicrons interact with tissues that have the enzyme lipoprotein lipase (muscle & adipose).
ApoC-2 activates lipoprotein lipase.
The enzyme then hydrolyzes TAG from chylomicrons, this action produces free fatty acid and 2-monoacylglycerol.
Once depleted of TAG, chylomicron "remnant" reenter circulation. [remnants may donate apolipoproteins to HDL].
Remnants travel to hepatocytes where LDL receptor-related protein 1 (LRP1) accepts apoE and the molecule is degraded.
Explain endogenous lipid transport
Lipid products carried to endoplasmic reticulum are assembled into VLDL with complimentary apolipoproteins (apoB-100, apoC-1, apoE) then secreted by exocytosis. Circulating VLDL acquires apoC-2 and more apoE from HDL. ApoC-2 allows VLDL to bind with lipoprotein lipase receptors.
In muscle: TAG is hydrolyzed to fatty acids and MAG to be used for energy.
In adipose: fatty acids are used for TAG synthesis.
The removal of lipid products transform VLDL into IDL, until all TAG is removed. Once TAG is depleted LDL is formed (only apoB-100 remains). LDL detaches and reenters circulation. LDL binds to LRP1 and is internalized by endocytosis.
internalized LDL is carried to lysosome which hydrolyze components. The free cholesterol is a signal that inhibits more LDL to enter into same cell .
Where is VLDL assemblemed?
In the liver
What is the main apoprotein associated with VLDL?
apoB-100, apoC-1, and apoE
What is the main apoprotein associated with LDL?
Where is apoA-1 formed?
in the liver and small intestine (may also be released from chylomicrons during TAG hydrolysis)
Explain reverse cholesterol transport
ApoA-1 binds to ABCA1 receptor, this allow apoA-1 to acquire phospholipids and free cholesterol from the hepatocyte which form nascent HDL. Nascent HDl also collects phospholipids and free cholesterol from interacting with ABCA1 and SR-B1 (muscle and adipose, and macrophages).
When nascent HDL collects lipids it acquires lecithin:cholesterol acyltransferase (LCAT) which catalyzes polyunsaturated fatty acids, from carbon 2 of phosphatidylcholine, on to the free cholesterol within the core. The particle then becomes a mature HDL.
Mature HDL binds to SR-B1 and ABCG1.
Further binding causes HDL to grow in size. HDL then uses cholesterol ester transferase protein (CETP) to distribute esters to VLDL and LDL, which reduces the size of the molecule.
HDL binds to SR-B1 of hepatocyte which allows for two actions:
1.) cholesterol esters may be selectively deposited into liver and depleted HDL returns to circulation.
2.) Entire HDL particle is degraded.
What is CETP?
Cholesterol ester transfer protein.
This protein allows for HDL to transfer cholesterol esters to VLDL & LDL for excretion.
WHat is the term used for a degenerative disease of vascular endothelium?
(which is caused by pro-inflammatory immune cells, cholesterol, and cholesterol esters)
What happens when arterial endothelial cells are injured?
monocytes and T lymphocytes accumulate in the area. cytokines (protein products) then signal phagocytic cells to the area.
What are foam cells?
Macrophages that have ingested LDL.
these cells infiltrate endothelium and develop into plaque. As lipids accumulate the vessel becomes occluded.
What is the lipid hypothesis?
Dietary lipid intake alter blood lipid levels which initiates or exacerbates atherogenesis.
What is the major component of atherogenic plaque?
How are LDL:HDL ratios reliably measured?
immunological methods of assessing apoB (LDL) and apoA-1 (HDL) ratio.
Which lipoprotein is antiatherogenic?
Which apoB protein can be found in fasted serum?
ApoB-48 & apoB-100 (which are components of VLDL, IDL, & LDL)
Total moles present in serum indicate potentially atherogenic particles.
When should apo ratio be tested and why?
During fasting state. So apoB-48 (from chylomicrons) does not contaminate the test.
What does research say about dietary cholesterol on the impact of serum cholesterol?
It has little impact, if any.
What is the American Heart Association recommendation for dietary cholesterol intake?
Since 2015, there is no limit.
what can be said about PUFA, MUFA, and SFA in regard to cholesterolemia?
SFA are hypercholesterolemic
PUFA are hypocholesterolemic
MUFA are neutral
What happens when SFA are replaced with CHO?
no benefit and may increase risk of CHD
Which specific fatty acids raise LDL (hyperchloremic) ?
Lauric acid (12:0)
mystric acid (14:0)
palmitic acid (16:0)
Which fatty acid lowers total cholesterol?
stearic acid (18:0)
WHat can be said about trans fatty acids and lipoproteins?
The raise LDL and Lower HDL
What is lipoprotein (a)?
a LDL particle containing apoB-100 linked to a glycoprotein.
It is associated with increase risk of CVD. serum Lp(a) is genetically determined.
Which form of apolipoprotein E has been associated with CVD and Alzheimer's?
ApoE4 (which is expressed high in europeans)
apoE4 can increase LDL's affinity for receptors on macrophages present in plaque tissue.
Recommended textbook explanations
Lehninger Principles of Biochemistry
David L Nelson, Michael M. Cox
Campbell Biology (AP Edition)
Cain, Campbell, Minorsky, Reece, Urry, Wasserman
Miller and Levine Biology
Joseph S. Levine, Kenneth R. Miller
Lisa A. Urry, Michael L. Cain, Peter V Minorsky, Steven A. Wasserman
Other sets by this creator
First 100 words
Eukaryote DNA replication
Prokaryote transcription and translation