Biochemistry-Fatty Acid Synthesis Flashcards
(32 cards)
If the de novo pathway is not significant in healthy people, why study it?
The pathway is significant in insulin-insensitive people, especially those with non-alcoholic fatty liver disease (NAFLD)
In what organs is the de novo pathway utilized?
Liver and brain (BBB does not allow passage of LCFAs, so it has to make them on its own)
How does the balance sheet turn out in a person who does not gain weight and eats carbs and fats?
At the end of a 24 hour period, all ingested CHO and fat is oxidized to CO2 and H2O.
Why does eating lots of sugar make you fat?
More carbohydrate is used as energy and keeps excess fat in your diet from being oxidized.
In the de novo fatty acid synthesis pathway, how does acetyl CoA from glucose get out of the mitochondria so it can continue through the pathway?
Acetyl CoA combines with oxaloacetate to form citrate. Citrate has a transporter that allows it to leave the matrix and get into the cytosol, where it is split back into acetyl CoA and oxaloacetate by citrate lyase.
Once you have acetyl CoA in the cytosol, how does fatty acid synthesis continue?
Acetyl CoA -> Malonyl CoA -> Numerous condensation reactions -> 16C Palmitic acid made by fatty acid synthase -> Converted to fatty acyl CoA -> Fatty acyl CoAs combine to form triglycerides -> packaged in VLDL -> taken out of liver
Purpose of VLDL sent out from the liver?
1) First it delivers triglycerides to adipose tissue and muscle -> triglycerides broken down to fatty acids by LPL -> fatty acids taken up by muscle and adipose -> adipose resynthesizes to triglycerides and stores them, muscle oxidizes them for energy 2) VLDL remnant is modified to IDL then LDL which can pick up cholesterol and take it back to the liver.
In order to get acetyl CoA into the cytosol from the mitochondrial matrix, you had to ship it out as citrate and then break it down to acetyl CoA and oxaloacetate. Why is oxaloacetate important in the cytosol?
Malate DH takes OAA -> Malate. Malate -> Pyruvate + CO2 + NADPH. NADPH is the reducing agent needed for fatty acid synthesis in the cytosol
Malate going to pyruvate will provide about 50% of your NADPH needed for fatty acid synthesis. How do you get the other 50%?
Pentose phosphate pathway.
What is the enzyme that catalyzes the committed step in fatty acid synthesis?
Acetyl CoA carboxylase. It takes Acetyl CoA + CO2 -> Malonyl CoA (the activated building block of acetyl CoA units)
What activates acetyl-CoA carboxylase? What inactivates it?
ACTIVATED: insulin, citrate, induction. INACTIVATED: glucagon, EPI, AMPK phosphorylation, repression
Why can’t we just reverse beta-oxidation to make fatty acids?
The thiolytic cleavage reaction is irreversible. Dehydrogenation steps can’t be reversed because the ratios of NADH/NAD+ and FADH2/FAD are unfavorable due to oxidative phosphorylation.
Why use NADPH for fatty acid synthesis?
The ratios are favorable in the cytoplasm for reduction.
Why is malonyl CoA the activated building block in fatty acid synthesis?
It can undergo a decarboxylation reaction before the condensation reaction. Irreversible decarboxylation is what allows the difficult condensation to proceed forward.
Where does malonyl CoA add onto in the synthesis of a fatty acid?
The head
What reactions are carried out by fatty acid synthase?
The opposite of the steps in beta-oxidation once you have the activated malonyl CoA. Malonyl ACP is decarboxylated -> 2 carbons are added to beta-keto FA head -> NADPH reduces beta keto group to alcohol -> H2O leaves and forms double bond -> NADPH reduces the double bond.
What is the long arm of fatty acid synthase that carries the fatty acid and the incoming malonyl CoA?
ACP (acyl carrier protein)
What is the overall reaction to synthesize on molecule of palmitate?
Note that this reaction results in a 25% loss in ATP because you need to burn a lot of glucose to make ATP and NADPH in order to get to palmitate.
How does fatty acid elongation take place at the face of the smooth ER?
SCoA is sticking out of the membrane, 2 carbons from malonyl CoA are added to the head, the beta ketone is reduced to an alcohol and then dehydrated to a double bond and then reduced, the new hydrophobic region slides down into the membrane
How does fatty acid desaturation take place at the face of the smooth ER?
Fatty acid desaturase binds the saturated fatty acid -> NADH transfers electrons to flavoprotein -> flavoprotein gives e- one at a time to cyt b5 -> oxygen receives electron and is activated -> oxygen is inserted into middle of hydrocarbon -> H2O is eliminated to form the double bond
What are the most common places to put double bonds when desaturating fatty acids?
9 position. You can also place them at the 4, 5 and 6 positions.
Why are omega 3’s and 6’s essential fatty acids?
Humans can’t place double bonds beyond the 9-10 position. You need these for eicosanoid synthesis.
What omega fatty acid is this?
Omega 7…you can number from the tail, note that the double bond will never get closer to the tail.
How do we prevent a futile cycle in fatty acid synthesis/beta oxidation?
When malonyl CoA is created by acetyl CoA, it also inhibits CPT1. CPT1 inhibits fatty acid transport into the mitochondrial matrix for beta oxidation. In a fasting state, you are not making malonyl CoA, CPT1 is active, and fatty acids move into the mitochondrial matrix for beta oxidation.
