Lecture 10 Flashcards
(27 cards)
What are the two primary reasons why you can store a lot more energy in lipids than in carbohydrates?
1) The level of the redox state in the Carbons in lipids.
Lipids have a more reduced state of carbon– from a metabolic standpoint as electrons are taken off of the lipids it’s going to lead to higher productions of NADH and FADH2 that can feed the electron transport chain of course that’s going to lead to more ATP.
2) Lipids are anhydrous. It is significantly less weight to store the same amount of energy in lipids.
Describe Triacylglycerides
Fats stored in body and fats ingested in the body. These are the most ingested fats we eat.
Sometimes these will be called storage lipids.
1) What are considered membrane lipids?
2) How many fatty acid chains are on these types of lipids?
3) What are the other components of this type of lipid?
1) Phospholipids.
Sphingolipids are considered a phospholipid and
play an important part of the membrane.
2) 2
3) a phosphate group on one end of the glyercol group. And off the end of the phosphate group is a head group.
TRUE or FALSE: Cholesterol plays an important role in membrane fluidity and is also the backbone for a lot of important molecules such as steroids.
True.
What is the only way to get rid of cholesterol?
Through bile salt and 50% of that is excreted through feces.
How do you make cholesteryl esters?
From Fatty acyl CoA you use that acyl chain (16-24 Carbon) group and put it on the hydroxyl of cholesterol.
Why are cholesteryl esters so hydrophobic?
Due to the hydrocarbon chain and ring structures.
Describe the overall breakdown of dietary lipids and how they are reformed and repackaged into chylomicrons which are then able to travel through the blood stream.
1) TAGs and other fats are broken down by bile salt and emulsified in the small intestine.
2) Pancreatic lipase and pancreatic phospholipase A2 is released into the small intestines and break down TAG into MAG (MonoAcylGlycerol) and 2 FFAs and PL and FFA respectively.
3) FFAs then are reformed into Acyl-CoA with the addition of CoA.
4) Acyl-CoA with the help of a bunch of enzymes are reformed into TAG through the addition of glycerol. Other Acyl-CoAs are reformed into Cholesterol Esters (cholesterol + acyl CoA).
5) These TAGs and CEs are then combined with Phospholipids, Apolipoproteins, and Cholesterol to create Chylomicrons which then travel the blood stream.
Where are chylomicrons made?
small intestines and that is where they are formed and then go into the body.
Why is the chylomicron hydrophilic?
Due to the monophospholipid layer and thus easier to travel.
As we look at lipoprotein particles a topic that often comes up is there “density.” What about the composition of each of these particles makes them less or more “dense”?
It’s the lipid to protein ratio.
Order the lipoproteins from smallest amount or proteins to most proteins and how does this protein to Triacylglyceride ratio affect density?
Chylomicrons have the least amount of proteins and the most triacylglycerides. Then, VLDLs, LDLs, and lastly HDLs have the highest density and the most proteins with the least amount of triaclyglycerides.
TRUE or FALSE: The more lipids you have the LESS dense it will be.
TRUE.
Sulfur, Nitrogen, and Oxygen which make up protein’s side chain versus a lipids CH3 chain are heavier in mass.
Describe the exogenous transport of dietary lipids.
They first start as chylomicrons formed in the small intestines. –.then they go through the lymph system up the thoratic duct and dump into the subclavin vein bypassing the liver. Then they are distibuted and diluted throughout the body to the capillary beds where (unlike carbs and amino acids) to the tissues first (versus the liver) where the tissues get to uptake lipids first and end in the liver as a REMNENT rather than start in the liver (like glucose would).
Then lipoprotein lipase is secreted and anchored to the epithelial cells of the capillary lumen and once in contact w/ ApoC II LPL becomes activated breaking down TAGs into glycerol and FFA. FFA are absorbed right here w/ the help of protein transports CD36 & FATP and glycerol travels to the liver or kindeys.
Then glycerol Kinase will phosphorylate this glycerol making glycerol-3-phosphate which has 3 different fates: phospolipids, TAGs, or glycolysis. Chylomicrons remnants are depleted of TAGs and ApoCII and is exchanged w/ ApoE (signals absorption in the live). Once in the liver remnant fuses with lysosome and broken down into smallest units.
Low density lipids have lots of lipids or lots or proteins comparivately to one another?
Lots of lipids since the weight of a lipid is much lower.
What are the 2 purposes of VLDL production? And
1) Transport excess dietary lipids and new lipids.–> This would be when in the FED STATE.
2) Transport FFA/TAG dervided from Adipose Tissue. FED STATE.
What does ACAT do?
It takes a cholesterol and makes Cholesteryl ester by tagging a fatty acyl group from Fatyy acyl-CoA.
About 50% of VLDLs will be TAGs. TRUE or FALSE
TRUE. They are lower in TAG contents compared to Chylomicrons but compared to LDLs and HDLs are much higher in TAGs.
VLDL’s rarely undergo endocytosis. IDL’s can undergo endocytosis but not nearly as much as LDL’s. Why?
SIZE. Due to protein to protein interaction. Apo B-100 is actually not exposed in the VLDL due to beefy size until it shrinks down to the size of an LDL.
HDLs are dervived from LDLs. TRUE or FLASE
FLASE. HDLs are made seperately in the liver.
What is familial hypercholesterolemia and what does it lead to? How is this condition
treated?
Familial Hypercheolesterolemia: autosomal dominant genetic disorder. People heterozygous for this have LDL >300mg/dl—> 1/2 of the LDL receptors are functional. Homozygous people (both copy of the genes are defective) have LDL >600mg/dl. MUTATIONS in LDL RECEPTOR—> prevents absorption of LDL particles from the bloodstream b/c the germline gene would affect all tissues. All versions of mutation = autosomal dominant.
PATHOLOGY of LDL accumulation: LDL have capacity to slip b/w endothelial cells & get into extracellular matrix outside the blood vessel & accumulate. These LDLs can undergo oxidation & become ox LDLs. This oxidative stress signals immune system monocytes to slip inb/w endothelial cells and convert to macrophage which can endocytose LDLs. Problem is that there is no stopping signal for macrophage to stop up taking LDL. This will then become a foam cell. These will then undergo Apoptosis, necrosis, leading to tissue damage, atherosclerosis, thrombosis, myocardial infarction, stroke. The content exploded into the extracellular matrix is hydrophobic, cholesterol rich, forming plaques. Cholesterol synthesis pathway: Acetyl-Co (which can come from many things) —> Beta-Hydroxy-Beta-methyl-glutaryl-CoA aka HMG-CoA. HMG-CoA reductase (rate limiting step) reduces HMG-CoA to Mevalonate. Mevalonate through ~20 steps is synthesized to cholesterol. Treatment for FH are drugs that inhibit HMG-CoA reductase which prevents HMG-CoA from forming Mevalonate and Mevalonate from forming endrogonic cholesterol inside the cell. So that if levels remain low inside the cell, the cell is more likely to take up cholesterol within circulation. There is a byproduct of cholesterol synthesis = oxysterols. Oxysterols will inhibit Receptor-Mediated Endocytosis. These drugs lower the amount of oxy sterols produced in the cells so that Receptor-Mediated Endocytosis continues occurring. There are a limited # of times LDL receptors can be recycled back to the cell membrane. Inhibition of LDL receptors (such as oxysterols or FH) will reduce the up take of circulating cholesterol and thus lead to the pathologies of plaque build up.
Treatment for FH
Treatment for FH are drugs that inhibit HMG-CoA reductase (rate limiting step) which prevents HMG-CoA from forming Mevalonate and Mevalonate from forming endrogonic cholesterol inside the cell. If levels remain low inside the cell, the cell is more likely to take up cholesterol within circulation. There is a byproduct of cholesterol synthesis = oxysterols. Oxysterols will inhibit Receptor-Mediated Endocytosis. These drugs lower the amount of oxy sterols produced from Acetyl-CoA in the cells so that Receptor-Mediated Endocytosis continues occurring. There are a limited # of times LDL receptors can be recycled back to the cell membrane. Inhibition of LDL receptors (such as oxysterols or FH) will reduce the up take of circulating cholesterol and thus lead to the pathologies of plaque build up.
