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What is the committed step of fatty acid synthesis
Aceteyl co A + ATP + HCO3- --> malonyl co A + ADP + Pi
Enzyme = acetyl co A carboxylase (biotin carboxylase and transcarboxylase)
Large negative change in G
What is the B vitamin in acetyl co A carboxylase? What is it's role?
Reacts with CO2 (HCO3-) to make a "charged" CO2 so it can transfer to acetyl co A
Where does fatty acid synthesis take place?
Where does B oxidation take place?
How does acetyl co A move from mitochondria to matrix?
Acetyl co A + OAA --> citrate
Citrate can translocate through the mitochondria membrane.
What is the role of citrate lyase?
Cleave citrate --> OAA + acetyl co A in the cytosol.
Uses ATP to do this
What is the fate of OAA in the cytosol
To be converted to malate (via malate dehydrogenase, NADH --> NAD+)
What is the fate of malate in the cytosol?
Can be translocated into cytosol or converted to pyruvate via malit. This reaction removes CO2 via oxidative decarboxylation. Generates a NADPH that can feed into fatty acid synthesis
What enzyme catalyzes the formation of fatty acids from malonyl co A?
fatty acid synthase complex
Contains 7 enzyme activities and contains an acyl carrier protein (ACP)
What is the B site?
B site contains pantothonic acid (reactive thiol) and adds malonyl co A via malonyl transferase activity
What is the C site
The C site contains a cystein (SH) and is part of the ACP portion of fatty acid synthase. Adds acetyl group of acetyl co A via acyl transferase activity. thioester bond
What are the steps to create a fatty acid after C site and B site are occupied?
- 1. Condensation--acyl group of C site condenses with CH2 of malonyl residue, releases a CO2. = 4 Carbon = B-ketoacyl
- (beta ketoacyl synthase)
- 2. Reduction of C=0 to form a hydroxyl group
- B-ketoacyl reductase
- 3. Dehydration to eliminate water and form a C=C
- (dehydrogatase enzyme)
- 4. Reduction of C=C using NADPH to get a fully saturated 4 carbon butyryl group.
- (reductase enzyme)
5. Move B ketoacyl butyryl group from B site to the C site, allow another acetyl malonyl to bind to B site.
6. Repeat up to 15 times
7. Cleave off C site with thioesterase to release FFA
How do you elongate a C-16 fatty acid?
Add malonyl co A to the fatty acid chain using enzymes (not fatty acid synthase enzymes)
Where does elongation occur?
On they cytoplasmic side of the ER in most tissues for up to C18. Brain can go up to C24.
Why are some fatty acids requires for us to eat?
We can't introduce double bonds past carbon 10 in the ER, so we need to consume these fats from our diet.
What enzyme makes double bonds to make a unsaturated fatty acid?
mixed function oxidases in the ER
What allosterically activates fatty acid synthase?
What allosterically inhibits fatty acid synthase
Activates = high levels of citrate (precursor for fatty acid synthesis)
Inhibits = palmityl CoA (product of fatty acid synthesis)
Which hormones stimulate phosphorylation of fatty acid synthase?
Glucagon and Epinephrine stimulate phosphorlation (and inactivation) of this enzyme
When is glucogon and epinephrine released?
Fasting conditions (dont want to make fats--need to break them down)
What effect does insulin have in the fatty acid synthesis pathway?
Stimulates citrate lyase to convert more citrate to acetyl co A.
Stimulates PDH complex to increase production of acetyl co A.
Both these effects will increase the amount of fatty acid synthesis
How is ACP similiar to co A?
ACP contains the B site which is made up of panthonic acid.
What is a benefit for converting malate to pyruvate in the cytosol?
Adds another NADPH that can be used for anabolic processes in the cytosol.
What would you like to do?
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