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Fatty Acid Synthesis
Occurs in three stages:
1. Mitochondrial acetyl-CoA gets exported to the cytoplasm
- Acetyl-CoA can not pass through the mictochonrial inner membrane
- Must be exported to the cytoplasm through the Citrate-Malate-Pyruvate Shuttle
2. Acetyl-CoA carboxylase (ACC) converts acetyl-CoA to malonyl-CoA
- This is the regulated and committed step
- Uses ATP
- Performs 2 reactions: carboxylation of biotin with ATP and transfer of carboxyl group to acetyl-CoA
https://fr.wikipedia.org/wiki/Fichier:MalonylCoA_synthesis_fr.png. Foobar. Creative Commons Attribution – Partage dans les Mêmes Conditions 3.0 (non transposée).
- Regulation of ACC:
- Activated by citrate
- Inhibited by phosphorylation and palmitoyl-CoA
- Malonyl-CoA inhibits carnitine acyltransferase 1 during beta oxidation
3. Fatty Acid Synthase (FAS) converts malonyl-CoA into fatty acid chains
- A large dimer with 10 active sites
- An Acyl Carrier Protein (ACP) contain a phosphopantetheine group
- Acetyl-CoA and malonyl-CoA bind to the ACP which condenses them to β-keto-acyl-ACP and CO2 is released
- Two redox reaction occur through β-ketoacyl reductase (KR) and β-enoyl reductase (ER)
- H2O is released by dehydratase (DH)
- The chain is then ready to accept 2 more carbons from malonyl-CoA
- Thioesterase (TE) adds an H2O to the fatty acid and releases it form the ACP
Wize Tip
To generate 16:0:
- 7 cycles of FAS
- 1 acetyl-CoA and 7 malonyl-CoA
- ACC requires 7 ATP and FAS uses 14 NADPH
Elongation
- Elongation of the 16:0 chain occurs in the ER
Denaturation
- Desaturases (require NADPH and O2) introduce double bonds within the first 9 carbons
- Anything past the 9th carbons comes from diet (omega 6 and omega 3)
Triacylglyceride Formation
- Occurs in liver and adipose tissue
- phosphatidate is converted to diacylglycerol by phosphatase
- diacylglycerol acyltransferase converts diacylglycerol to tri-acyl-glycerol.
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Which of the following are steps involved in fatty acid synthesis. Choose all that apply.
a. Conversion of acetyl-CoA to malonyl-CoA by ACC
b. Synthesis of fatty acid chains by FAS
c. Beta oxidation in the mitochondrial matrix
d. Export of acetyl-CoA from the mitochondria to the cytoplasm
a, b, and d. Beta-oxidation is involved in fat catabolism.