Triglyceride Metabolism & Fatty Acid Synthesis Flashcards
How many essential lipids are there? What are they?
- 6 essential lipids: 2 essential FAs (linoleic FA and linolenic FA) + the 4 fat-soluble vitamins (A,D,E, and K)
Why are linoleic FA and linolenic FA essential FAs?
- because these FAs have double bonds past the 9th carbon
- our bodies can make any FA that has any number of double bonds, so long as the double bonds are no on C9 or higher
cis- vs. trans-FAs
- all naturally occurring unsaturated FAs have double bonds in the cis-configuration
- cis allows for membrane fluidity by providing a “kink” in the membrane, trans does not (same reason why saturated FAs are bad, as well)
What goes a triglyceride break down into during digestion?
- 1 molecule of 2-monoacylgylcerol and 2 molecules of free fatty acids
When do blood triglyceride levels reach a max after eating a meal?
- about 4-5 hours after
- (vs. glucose, which reaches a max blood level in only 45 minutes)
What type of lipid will we find in the stool of a patient with no bile? With no pancreatic lipase? With malabsorption?
- no bile = triglycerides
- no lipase = triglycerides
- malabsorption = fatty acids
Where and when does fatty acid synthesis occur?
- occurs mainly in the liver (remember that the liver has mechanisms to keep glycolysis running even when large amounts of ATP have already been generated)
- in the cytoplasm
- occurs when we eat a high carb meal (we turn excess sugar into FA for storage)
What are the 4 ingredients for fatty acid synthesis? Where do these ingredients come from?
- acetyl CoA: from citrate
- NADPH: from the HMP shunt
- CO2: present in a dissolved form basically everywhere
- ATP: from glycolysis, citric acid cycle, and electron transport chain
The acetyl-CoA needed for fatty acid synthesis is derived from citrate, but F.A.S. occurs in the cytoplasm, and citrate is in the mitochondria - explain what happens.
- once isocitrate dehydrogenase is inhibited by ATP and NADH, the citric acid cycle is terminated and citrate concentrations elevate in the mitochondria, allowing some to enter the cytoplasm
- in the cytoplasm, citrate can be made into acetyl-CoA
Which enzyme converts acetyl-CoA into ________? What does the enzyme need to function? What is this reaction regulated by?
- acetyl-CoA carboxylase converts acetyl-CoA into malonyl-CoA
- this is an “ABC” enzyme, requiring ATP, biotin (B7), and CO2 to function (3 “ABC” enzymes, the other 2: pyruvate carboxylase (gluconeogenesis) and propionyl-CoA carboxylase (B-oxidation of odd FAs)
- activated allosterically by citrate, genetically by insulin, and via dephosphorylation by insulin
- deactivated via phosphorylation by glucagon
What happens to malonyl-CoA?
- gets acted on by fatty acid synthase to generate fatty acid palmitate
- this reaction requires NADPH
What kind of FA is fatty acid palmitate? What happens to it?
- fatty acid palmitate is a 16:0 FA (16 carbons, no double bonds - saturated)
- it gets shipped to the ER where it can be elongated and desaturated to form other FAs (remember that we can NOT place double bonds on carbons 9 or higher)
What happens to fatty acids once they are synthesized?
- they are made into triglycerides and shipped to adipose tissue for storage via VLDL
Explain the biochemistry in alcoholic fatty liver disease.
- alcohol disrupts VLDL formation/assembly, so the triglycerides are unable to leave the liver = build up = fatty liver
What are the ingredients for triglyceride synthesis? Where do they come from?
- 3 fatty acid-CoA (from F.A.S.) and a glycerol backbone (from dihydroxyacetone phosphate/DHAP via glycolysis and from recycled glycerol)
- (DHAP gets converted into glycerol-3-P)