2- Lipid Synthesis and Storage Flashcards
When does fatty acid biosynthesis occur?
In the Insulin world. In the fed state
What are the ingredients for FA?
AcetylCoA- from citrate
CO2- from blood stream
NADPH - from HMP shunt (G6PD) and malate
ATP- mitochondria
Draw pathway from citrate to FA synthesis
citrate moved to cytoplasm
citrate > Acetyl CoA + CO2 (use ATP) > Malynyl CoA + NADPH > Fatty acid Palmitate + CO2
enzymes:
AcetylCoA carboxylase (ABC): acetyl CoA > Malynyl CoA
Fatty Acid Synthase: malynyl CoA + NADPH > fatty acid
palmitate
Fatty acid palmitate is the only FA made by scratch
Acetyl CoA carboxylase
ABC, acetyl CoA, biotin, CO2
Activated (+) by insulin and citrate
Inhibited by glucagon, and palmitoyl CoA
Co2 + Acetyl CoA (2C) > malynyl CoA
AcCoA carboxylase regulates fatty acid synthesis
What happens to FA after synthesis?
FA moves from cytoplasm to smooth ER.
FA elongated and desaturated (is that all?) in the ER.
FA then made into triglyceride, in the liver.
TGL combines with app-B100 (VLDL)
Then shifted into adipocytes.
How is fat absorbed from the gut?
lacteals (lymphatic vessels) so that blood is not clogged with fats.
Goes straight to the right atrium where it meets up with apoproteins and then gets shipped to the liver.
Whereas protein and glucose goes to the hepatic portal vein to the liver.
Why are alcoholics liver fatty?
alcohol stops VLDL from leaving the liver.
Alcohol disrupts VLDL assembly, TG stay in liver
Alcohol is found in the liver because it is absorbed very fast and will get to the hepatic portal vein to the liver. Also where alcohol dehydrogenase is found.
What does Malonyl CoA inhibit?
carnitine acyltransferase I
in order to prevent import and degradation of newly synthesized fatty acylCOA (?)
What are the 3 control points of FA synthesis?
Acetyl CoA
Malonyl CoA
Palmitoyl CoA
LPL
lipoprotein lipase- enzyme to facilitate movement of fat into the cell
Insulin activates it. So in diabetics, fats are made but can’t be stored
What are the sources of glycerol in the liver?
2 sources:
DHAP from glycolysis
Glycerol from the liver itself
Why is insulin important for FA synthesis? what all does it do?
- Activates AcCoA carboxylase to turn on FA synthesis
- Turns on gene for for LPL in adipocytes
- Forces the liver to make TGL in abundance
-Also turns on glucokinase and PFK-2 in the liver during glycolysis
Why can’t TGL be stored in the liver in abundance?
Because TGLs are non polar, liver does not fit them well.
Adipocytes, however, are 90% anhydrous (do not contain water)
Where does cholesterol come from?
- Cholesterol itself- polar OH, can dissolve in some water.
- Cholesterol ester - nonpolar, does not mix in blood.
Recommended daily dose of cholesterol
300 mg
Cholesterol digestion
Chol and cholesterol ester are emulsified by bile and pancreatic esterase. Enzyme removes FA off of CE so that it can be absorbed into intestines
After absorbed, ACAT puts FA into Chol remaking CE (in intestinal mucosa)
CE packaged with TG+PL+ApoB-48 > Chylomicrons
Goes to lymph then blood stream via thoracic duct
Chylomicron
ApoB-48
delivers dietary fats to tissues
lowest density chylomicrons
What are the three types of lipase that break ester bonds of TGs?
- Pancreatic lipase- breaks down TGL
- LPL (lipoprotein lipase)- in lipoprotein metabolism. important for uptake into adipocytes
- HSL- hormone sensitive lipase- in adipocytes where it hydrolyzes stored triglycerides to free fatty acids.
Normal blood cholesterol levels?
200 mg/dl
after meal takes 5-7 hours to return to normal levels. (compared to glucose takes 1-2 hours)
Apo proteins and types
The protein part of lipoprotein
ApoA- activator of LCAT (enzyme found in blood)
ApoB- involved in receptor lipoprotein interactions
ApoE- involved in receptor lipoprotein interactions
ApoC- activator of LPL
Draw the pathway of lipoproteins from intestine to destination.
Mucosal cells absorbs FA + Cholesterol, intestine, TGL and CE reunited in
Intestine > lymph chylomicron, (TGL some CE and apoB48 on surface)
Lymph > blood stream via thoracic duct > left subclavian vein > RA of heart (where fat and apo protein mix)
HDL donates ApoC and ApoE in blood > join chylomicron
ApoC activates LPL in adipocytes > LPL breaks down lipoproteins and TGL to FA > stored as TGL
ApoC is give back to HDL > Chylomicron starts to shrink > now chylomicron remnant (residual TGL, CE, apoE and apoB-48)
Remnant receptors on liver dock with apoE and apoB > endocytosis into liver > esterasere (cleaves CE) > FA and cholesterol
How long after high carb meal can TGL be used?
90 - 120 minutes.
Chylomicron remnant
After LPL does it’s job chylomicron now just ApoE ApoB-48 and residual TGL and some CE.
Attaches to remnant receptor in liver
What is the liver going to do with dietary cholesterol?
send out to blood as VLDL (mostly TGL and Chol.) and surface is apoB100.
VLDL will encounter HDL. HDL gives ApoC and Apo E
VLDL will now activate LPL when near. Take in TGL and cleave 3FA + glycerol
Becomes IDL which goes to liver.
