Fatty acid Synthesis Flashcards
Is fatty acid synthesis the reverse of beta oxidation?
No
Where does fatty acid synthesis take place?
Takes place in our liver cells and in lactating mammary glands
In which part of the cell does fatty acid synthesis occur?
In the cytosol
How is citrate shuttled out of the inner mitochondrial membrane?
Via the pyruvate malate cycle
Why is the pyruvate malate cycle important?
- It shuttles out our citrate
2. Helps generate NADPH for the pentose phosphate cycle
Name the 3 carbon intermediate that is important or fast acid synthesis to occur
Malonyl CoA
How is malonyl CoA formation require?
Acetyl CoA in an irreversible reaction
Name the rate determining step for fatty acid synthesis
The formation of malonyl CoA
How is malonyl CoA formed?
Acetyl CoA reacts with Acetyl CoA carboxylase (biotin) and citrate to form malonyl CoA
State the 2 equators involved in the production of malonyl CoA
- Biotin-enzyme + ATP + HCO3 -> CO2-Biotin-enzyme + ADP+ Pi
2. CO2-Biotin-enzyme + acetyle CoA -> malonyl CoA + Biotin-enzyme
Name a step which inhibits or activates fatty acid synthesis
The formation of malonyl CoA
How is the formation of malonyl CoA regulated?
By regulating the enzyme acetyl CoA carboxylase
When do we want a lot of malonyl CoA to be produced?
When we have a low AMP:ATP ratio (ie when we don’t have a lot of energy)
How is Acetyl CoA
carboxylase inactivated?
When there’s a high AMP:ATP ratio up regulates kinase phosphorylating our Acetyl CoA
carboxylase inactivating it
How is Acetyl CoA
carboxylase activated?
Increased insulin and decreased glucagon up regulates Phosphatase which removes a phosphate group from Acetyl CoA
carboxylase activating it
What does the fatty enzyme synthase complex do?
It catalyses different enzymatic activities to synthesis and elongate fatty acids
Describe the central part of the fatty acid synthesis complex
It is a domain where the molecule 4’ phosphopentetheine covalently bonds to the enzyme
What is 4’ phosphopentetheine ?
It is a derivative of the vitamin pantothenic acid and it is also a component of CoA
What does 4’ phosphopentetheine do?
It carries acetyl and act units on the terminal thiol group during fatty acid synthesis
Name all the steps of fatty acid synthesis
- Transfer from acetyl CoA to the SH group of the Acyl Carrier Protein
- Transfer of a 2 carbon fragment on our ACP onto a cystine residue on the enzyme
- Addition of the malonate unit from malonyl CoA onto a vacant ACP
- Acetyl attack the malonyl group
- Reduction of acetoacetyl-S-ACP
- Dehydration of beta-hydroxybutyryl-ACP to introduce a double bond
- Reduction of crotonyl-S-ACP
How is acetyl CoA transferred onto the acyl carrier protein (ACP)?
Via the enzyme Acetyl CoA-ACP transacylase
this forms Acetyl-S-CAP + CoA
What does Acetyl CoA-ACP transacylase do?
It transfers acetyl CoA transferred onto the acyl carrier protein (ACP)
What happens to Acetyl-S-CAP once it has formed?
It combines with an enzyme-sulpha hydrate too form Acetyl-S-Enzyme + ACP-SH
(no enzyme required)
What is malonate added to and how
Malonyl CoA is reacted with ACP-SH via the enzyme Malonyl CoA-ACP-transacylase
to form Malonyl-S-ACP + CoA
What does Malonyl CoA-ACP-transacylase do?
Reacts Malonyl CoA and ACP-SH together to form malonyl-S-ACP +CoA
What happens to Malonyl-S-ACP once it has formed?
It is attacked by acetyl groups
What happens to malonyl S ACP once it is attacked by acetyl groups?
It loses a CO2
Why is malonyl-S-ACP losing CO2 an important step?
It is a key step in providing the reaction with energy as the decarboxylation drives the reaction
How does the malonyl-S-ACP lose a CO2?
It undergoes an acetyl attack and is reacted with the enzyme B-Ketoacyl-ACP synthase to form acetoacetyl-S-ACP
What does B-Ketoacyl-ACP synthase do?
It aids in the conversions of malonyl-S-ACP into acetoacetyl-S-ACP
What happens to acetoacetyl-S-ACP once it has formed?
It Is reduced by NADPH to for beta-hydroxybutyryl-ACP by the enzyme b-Ketoacyl-ACP reductase
What does the enzyme b-Ketoacyl-ACP reductase do?
It aids in the reduction of acetoacetyl-S-ACP into beta-hydroxybutyryl-ACP
What happens to beta-hydroxybutyryl-ACP once it as formed?
It is dehydrated by b-hydroxyacyl-ACP
dehydratase to form crotonyl-S-ACP
What does b-hydroxyacyl-ACP
dehydratase do?
It dehydrates beta-hydroxybutyryl-ACP to form crotonyl-S-ACP
What happens to crotonyl-S-ACP once it has formed?
It is reduced by NADP and Enoyl-ACP reductase do form butyryl-S-ACP + NADP+
What doesEnoyl-ACP reductase do?
It reduces crotonyl-S-ACP to form butyryl-S-ACP
At the end of the 7 steps of fatty acid synthesis what is produced?
A 4 carbon compound is produced which has 3 terminal carbons fully saturated
After the 7 steps of fatty acid synthesis what happens?
These 7 steps are repeated in the sequence 5 times beginning with the transfer of the newly formed 4 carbon species from the ACP to the peripheral cysteine side group
After the sequence of fatty acid produce has been repeated 6 times what is the end result?
The cycle is repeated until a fully saturate 16 carbon long fatty acid chain forms
What happens when a fatty acid with 16 carbons is synthesised?
The synthetic process is terminated as a fully saturated molecule of palmitate is formed
State the overall reaction for palmitate synthesis
8Acetyl CoA + 14NADPH + 14H+ +7ATP
->
Palmitate + 14NADP+ +8CoA +7ADP +H2O