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61 Cards in this Set

  • Front
  • Back
triacylglycerol
fats or triglycerides

major form of metabolic energy storage
what determines rate of digestion?
surface area and actions of bile acids
What are bile acids?
-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
What is triacylglycerol lipase?
-pancreatic lipase
-catalyze hydrolysis of 1 and 3 positions of triaclglycerols to form 1,2-diacylgycerols and 2-acylglycerols
What is interfacial activation?
-enzyme activity of lipase increases when it contacts lipid-water inteface
What is colipase?
-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
Pancreatic Lipase (449 residues)
-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
what does phosphatidylcholine participate in?
helps bind lipase to interface with bile acids and colipase
What is B5 loop?
it is part of the pancreatic lipase and it helps form the oxyanion hole and generates a hydrophobic surface near entrance of active site.
where is the active site of the pancreatic lipase?
it's in the N-terminal domain
where does colipase bind to in the pancreatic lipase?
it binds to the C-terminal domain
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).
What does the intestinal mucosal do?
it absorbs fatty acids produced by lipid digestion
micelles of Bile acid
transport lipid degradation products to intestinal wall and helps absorption of vitamins K,A,D,E
What does I-FABP do?
-cytoplasmic protein
-increases effective solubility of water-soluble substances
-protects cell from detergent-like effects
What is I-FABP?
-intestinal fatty acid-binding protein
-fatty acids bind to I-FABP inside intestinal cells
What is the structure of I-FABP?
-131 residues
-10 antiparallel B strands stacked in two B sheets.
How does fatty acid bind to I-FABP?
-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
What are lipoproteins?
-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
What are the 5 types of lipoproteins?
1.chylomicrons
2.VLDL
3.IDL
4.LDL
5.HDL
Chylomicrons
-packaged triacylglycerols
-released into intestinal lymph and transported through lymphatic vessels before draining into large veins and then into bloodstream
VLDL
-very low density lipoproteins
-transport endogenous triacyglycerols and cholesterol from liver to tissues
IDL
-Intermediate density lipoprotein
-transport endogenous triacyglycerols and cholesterol from liver to tissues
LDL
-low density lipoprotein
-transport endogenous triacyglycerols and cholesterol from liver to tissues
HDL
-high density lipoprotein
-transport cholesterol from tissue to liver
-smallest lipoprotein
What is apolipoproteins/apoproteins?
they are the protein part of lipoproteins
What is apoB-100?
-apolipoprotein B-100
-4536 residue monomer
-LDL has this
-high hydrophobicity
properties of apoproteins
-water soluble
-associate weakly with lipproteins
-high helix content, which increases when they bind with lipoproteins
-contact with hydrophobic surface favors formation of helices
helices in apoprotein
have hydrophilic and hydrophobic side chains so lipoproteins are like logs on water
what is apoA-I?
-apolipoproteinA-I
-occurs in chylomicrons and HDL
What does chylomicrons do?
-deliver triaclglycerols to muscles and adipose tissue and cholesterol to liver
-bind to inner surface of capillaries
what does lipoprotein lipase do to chylomicrons?
triacylglycerol in chylomicrons are hydrolyzed by lipoprotein lipase where tissues then take up freed monoacylglycerol and fatty acids
what happens after chylomicrons are used up?
they shrink and become remnants which dissociate from capillaries and get taken up by liver again
What do VLDL do?
they transport endogenous triacylglycerols and cholesterol
what does lipoprotein lipase do to VLDL?
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
what is dihydroxyacetone phosphate?
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
what happens to VLDL remnants?
turns into IDL and then to LDL. Half of the products is taken up by liver.
how do cells take up LDL?
through receptor mediated endocytosis
how does cell get cholesterol?
body synthesizes it or take it from LDL, rich in cholesterol and cholesteryl esters
what does LDL receptors do?
they isolate LDL by binding specifically to apoB-100 on the cell surface
what are clathrin-coated pits?
group of LDL receptors
what are clathrin-coated vesicles?
they form after apoB-100 of LDL binds to receptor and is transported into cell
what happens to clathrin-coated vesicles after it enters cell?
fuses with endosomes (internal pH~5), results in LDL to dissociate from receptor and receptor goes back to membrane surface,
what happens to endosome with LDL after receptors go back to membrane surface?
endosome with LDL fuses with lysosomes
what happens in lysosomes after it fuses with endosomes with LDL?
LDL's apoB-100 degrade to amino acids and cholesteryl esters are hydrolyzed to give cholesterol and fatty acids
what controls rate of LDL receptor synthesis?
intracellular concentration of free cholesterol
what happens with defects in LDL receptor system?
abnormal high levels of cholesterol leading to risk of heart disease
where is LDL receptor synthesized and how does it get to cell surface?
made in the endoplasmic reticulum and processed in golgi apparatus and inserted into plasma membrane, to become part of clathrin-coated pits
what are clathrin triskelions?
outside of clathrin-coated vesicles are clathrin triskelions. when vesicle fuse with endosome, triskelions recycle back to cell surface
ACAT
-acyl-CoA:cholesterol acyltransfersase
-converst cholesterol into cholesteryl esters
HMG-CoA reductase
-part of getting cholesterol
-catalyze cholesterol biosynthesis
what does a lot of cholesterol do to HMG-CoA, LDL receptors, and ACAT?
decreases HMG-CoA and LDL receptors while increases ACAT
What does HDL do and how?
transports cholesterol from tissues to liver by taking it from cell surface of membrance (HDL is in the plasma)
LCAT
-lecithin-cholesterol acyltransferase
-converts cholesterol into cholesteryl esters
-activated by apoA-I
SR-BI
HDL binds to receptor SR-BI and gives components to liver cell.
how do you dipose of cholesterol?
convert to bile acids in liver
what does serum albumin do?
free fatty acids bind to serum albumin for transport to tissues
what is the Franz Koop Experiment?
suggested that fatty acids are oxidized on B-carbons: B-oxidation
what does acyl-CoA synthetase do?
-several forms specific for different chain lengths
-associated with mitochondrial outer membrane
reaction of activation of fatty acids
Fatty Acid + ATP + CoA <=> Acyl-CoA + AMP + PPi
activation of fatty acids
reaction driven by hydrolysis of PPI, overall gibs free engery = -34 kJ/mole.