Fatty Acid Synthesis Flashcards
Where does fatty acid synthesis occur?
in the cytosol or cytoplasm
The building block of fatty acids is
acetyl CoA
Where is acetyl CoA produced?
in the matrix of the mitochondria
What rxn begins fatty acid synthesis?
irreversible carboxylation of acetyl CoA
What does the carboxylation of acetyl CoA result in?
generates malonyl CoA and commits the acetyl group to fatty acid synthesis
What enzyme and cofactor catalyze the carboxylation of acetyl CoA?
acetyl CoA carboxylase and biotin
What factors promote the process of fatty acid synthesis?
High levels of citrate and ATP
What 3 things does every carboxylase require?
- an energy source (ATP)
- a carbon source (HCO3-)
- a cofactor( biotin, i.e. vitamin B7)
What is the rate limiting step of the entire rxn?
the conversion of acetyl CoA to malonyl CoA
Which enzyme is regulated to either inhibit or activate fatty acid synthesis?
acetyl CoA carboxylase
ACP means …
Acyl Carrier Protein
What does FAS stand for and what does it do?
Fatty acid synthase and it is an enzyme that catalyzes all the 7 steps of fatty acid synthesis
Describe FAS
a single polypeptide chain that contains 7 different catalytic sites and domains as well as an ACP domain
Describe ACP
contains a phosphopantetheine group which contains a sulfhydryl group which allows the binding of certain molecules
Step 1
- catalyzed by acetyl transacylase
2. acetyl CoA attaches to sulfhydryl of ACP and an intermediate is formed
Step 2
transfer of acetyl group from sulfhydryl of ACP to cysteine which acts as a temporary holding group
Step 3
malonyl transacylase catalyzes the formation of a bond between malonyl CoA with ACP
an intermediate with an acetyl group attached to the cysteine group and malonyl group attached to ACP is formed
Difference between acetyl transacylase and malonyl transacylase
acetyl tranacylase is less specific to its substrate
What’s the importance of step 3?
prepares the molecule for elongation of the fatty acid chain
What makes step 4 a crucial step?
it drives the entire rxn forward
Step 4
- decarboxylation and condensation step
- acyl malonyl ACP condensing enzyme decarboxylates the carbonyl end of malonyl and prepares the 2 molecules for nucleophilic attack
- acetyl group moves from the cysteine group to ACP
- acetoacetyl is formed as a product and is still attached to ACP
Step 5
- reduction step
- NADPH is reducing agent
- NADPH reduces the terminal carbonyl group to an alcohol
- β-ketoacyl ACP reductase catalyzes this rxn
- D-3-hydroxybutyryl is the product
Step 6
- dehydration step
- catalyzed by dehydroxyacyl ACP dehydratase
- double bond is generated and water is released
- crotonyl is produced and remains attached to ACP
Step 7
- 2nd reduction step
- NADPH is also reducing agent
- catalyzed by enoyl ACP reductase
- butyryl group is generated and still attached to ACP
- completes 1st elongation step
What can be observed from steps 5-7 and why?
double bonds are removed by converting a β-keto group to a methylene group in order to produce a saturated fatty acid
How many more times will the process take place to generate a 16C palmitate fatty acid molecule?
6
What happens in the next step after butyryl group is formed?
the butyryl group is transferred from ACP to cysteine group for temporary holding
another malonyl CoA will attach to the ACP and steps 2-7 will be repeated until palmitate is formed
What happens once 16C palmitate fatty acid is formed?
thioesterase, an enzyme, cleaves the palmitate-ACP bond and releases the palmitate molecule
