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61 Cards in this Set
- Front
- Back
triacylglycerol
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fats or triglycerides
major form of metabolic energy storage |
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what determines rate of digestion?
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surface area and actions of bile acids
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What are bile acids?
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-Solubilize fat globules (liver digestion and absorption of liver products)
-cholesterol derivatives synthesized by liver and secreted as glycine or taurine conugates into the gallbladder for storage. They are then secreted into small intestines |
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What is triacylglycerol lipase?
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-pancreatic lipase
-catalyze hydrolysis of 1 and 3 positions of triaclglycerols to form 1,2-diacylgycerols and 2-acylglycerols |
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What is interfacial activation?
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-enzyme activity of lipase increases when it contacts lipid-water inteface
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What is colipase?
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-90 residue protein that forms 1:1 complex with lipase.
-helps form hydrophobic tips of 3 loops (phosphatidylcholine, bile acids, colipase) to form hydrophobic plateau which helps with binding lipase to lipid surface. -forms 3 hydrogen bonds to opened lid to stabilize it |
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Pancreatic Lipase (449 residues)
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-Active site is in N-terminal domain (1-336)
-without micelles, active site is covered by 25-residue helicial lid -with micelles, lid allows exposure of active site -B5 loop forms oxyanion hole and generates a hydrophobic surface near entrance of active site -colipase binds to C-terminal domain (337-449) to help form hydrophobic plateau to bind lipase to lipid surface |
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what does phosphatidylcholine participate in?
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helps bind lipase to interface with bile acids and colipase
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What is B5 loop?
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it is part of the pancreatic lipase and it helps form the oxyanion hole and generates a hydrophobic surface near entrance of active site.
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where is the active site of the pancreatic lipase?
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it's in the N-terminal domain
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where does colipase bind to in the pancreatic lipase?
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it binds to the C-terminal domain
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phospholipase A2
What's so special about it? |
-this enzyme contains a hydrophobic channel that provides direct access for substrate to active site of enzyme.
-soluble and dispersed phospholipids must first surmount kinetic barriers to bind to enzymes (substrates have to go through a lot to get direct access). |
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What does the intestinal mucosal do?
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it absorbs fatty acids produced by lipid digestion
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micelles of Bile acid
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transport lipid degradation products to intestinal wall and helps absorption of vitamins K,A,D,E
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What does I-FABP do?
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-cytoplasmic protein
-increases effective solubility of water-soluble substances -protects cell from detergent-like effects |
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What is I-FABP?
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-intestinal fatty acid-binding protein
-fatty acids bind to I-FABP inside intestinal cells |
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What is the structure of I-FABP?
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-131 residues
-10 antiparallel B strands stacked in two B sheets. |
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How does fatty acid bind to I-FABP?
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-fatty acid takes up the space between the two B strands.
-fatty acid's carboxyl group interacts with Arg106, Glu115, and two bound water molecules |
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What are lipoproteins?
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-they are globular micelle-like particles that consist of a nonpolar core of triacylglycerols and cholesteryl esters surrounded by an amphilic coating of protein, phospholipid, and cholesterol
-20 A thick monolayer of protein, phospholipid, and cholesterol on particle surface -densities increase with decrease particle diameter because density of outer coating is great than inner |
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What are the 5 types of lipoproteins?
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1.chylomicrons
2.VLDL 3.IDL 4.LDL 5.HDL |
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Chylomicrons
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-packaged triacylglycerols
-released into intestinal lymph and transported through lymphatic vessels before draining into large veins and then into bloodstream |
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VLDL
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-very low density lipoproteins
-transport endogenous triacyglycerols and cholesterol from liver to tissues |
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IDL
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-Intermediate density lipoprotein
-transport endogenous triacyglycerols and cholesterol from liver to tissues |
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LDL
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-low density lipoprotein
-transport endogenous triacyglycerols and cholesterol from liver to tissues |
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HDL
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-high density lipoprotein
-transport cholesterol from tissue to liver -smallest lipoprotein |
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What is apolipoproteins/apoproteins?
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they are the protein part of lipoproteins
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What is apoB-100?
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-apolipoprotein B-100
-4536 residue monomer -LDL has this -high hydrophobicity |
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properties of apoproteins
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-water soluble
-associate weakly with lipproteins -high helix content, which increases when they bind with lipoproteins -contact with hydrophobic surface favors formation of helices |
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helices in apoprotein
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have hydrophilic and hydrophobic side chains so lipoproteins are like logs on water
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what is apoA-I?
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-apolipoproteinA-I
-occurs in chylomicrons and HDL |
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What does chylomicrons do?
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-deliver triaclglycerols to muscles and adipose tissue and cholesterol to liver
-bind to inner surface of capillaries |
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what does lipoprotein lipase do to chylomicrons?
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triacylglycerol in chylomicrons are hydrolyzed by lipoprotein lipase where tissues then take up freed monoacylglycerol and fatty acids
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what happens after chylomicrons are used up?
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they shrink and become remnants which dissociate from capillaries and get taken up by liver again
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What do VLDL do?
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they transport endogenous triacylglycerols and cholesterol
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what does lipoprotein lipase do to VLDL?
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lipoprotein lipase degrades VLDL in capillaries, which gives fatty acids. The fatty acids are used by cells or used to remake triacylglycerols while the glycerol is transported to liver/kidneys to convert to glycolytic intermediate dihydroxyacetone phosphate
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what is dihydroxyacetone phosphate?
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glycerol from degradation of VLDL is transported to liver/kidneys to convert this this glycolytic intermediate, which is 3 carbons. oxidation of this gives very little energy
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what happens to VLDL remnants?
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turns into IDL and then to LDL. Half of the products is taken up by liver.
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how do cells take up LDL?
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through receptor mediated endocytosis
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how does cell get cholesterol?
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body synthesizes it or take it from LDL, rich in cholesterol and cholesteryl esters
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what does LDL receptors do?
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they isolate LDL by binding specifically to apoB-100 on the cell surface
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what are clathrin-coated pits?
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group of LDL receptors
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what are clathrin-coated vesicles?
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they form after apoB-100 of LDL binds to receptor and is transported into cell
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what happens to clathrin-coated vesicles after it enters cell?
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fuses with endosomes (internal pH~5), results in LDL to dissociate from receptor and receptor goes back to membrane surface,
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what happens to endosome with LDL after receptors go back to membrane surface?
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endosome with LDL fuses with lysosomes
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what happens in lysosomes after it fuses with endosomes with LDL?
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LDL's apoB-100 degrade to amino acids and cholesteryl esters are hydrolyzed to give cholesterol and fatty acids
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what controls rate of LDL receptor synthesis?
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intracellular concentration of free cholesterol
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what happens with defects in LDL receptor system?
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abnormal high levels of cholesterol leading to risk of heart disease
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where is LDL receptor synthesized and how does it get to cell surface?
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made in the endoplasmic reticulum and processed in golgi apparatus and inserted into plasma membrane, to become part of clathrin-coated pits
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what are clathrin triskelions?
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outside of clathrin-coated vesicles are clathrin triskelions. when vesicle fuse with endosome, triskelions recycle back to cell surface
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ACAT
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-acyl-CoA:cholesterol acyltransfersase
-converst cholesterol into cholesteryl esters |
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HMG-CoA reductase
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-part of getting cholesterol
-catalyze cholesterol biosynthesis |
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what does a lot of cholesterol do to HMG-CoA, LDL receptors, and ACAT?
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decreases HMG-CoA and LDL receptors while increases ACAT
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What does HDL do and how?
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transports cholesterol from tissues to liver by taking it from cell surface of membrance (HDL is in the plasma)
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LCAT
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-lecithin-cholesterol acyltransferase
-converts cholesterol into cholesteryl esters -activated by apoA-I |
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SR-BI
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HDL binds to receptor SR-BI and gives components to liver cell.
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how do you dipose of cholesterol?
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convert to bile acids in liver
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what does serum albumin do?
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free fatty acids bind to serum albumin for transport to tissues
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what is the Franz Koop Experiment?
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suggested that fatty acids are oxidized on B-carbons: B-oxidation
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what does acyl-CoA synthetase do?
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-several forms specific for different chain lengths
-associated with mitochondrial outer membrane |
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reaction of activation of fatty acids
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Fatty Acid + ATP + CoA <=> Acyl-CoA + AMP + PPi
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activation of fatty acids
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reaction driven by hydrolysis of PPI, overall gibs free engery = -34 kJ/mole.
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