Fatty Acid Synthesis. Flashcards
What is prosthetic group?
A cofactor or coenzyme that is often covalently bonded to the enzyme.
What is enzyme induction?
The up-regulation or synthesis of more of a particular enzyme.
De-novo fatty acid synthesis in humans take place?
In the liver and in the lactating mammary gland.
What will the liver use to make fatty acids?
Glucose.
Why will the liver make fatty acids?
To reduce blood glucose levels.
What condition will the synthesis of fatty acids prevent?
Hyperglycaemia.
Will the liver ever store fat?
No.
Fat is always stored in the fat cells.
What organelle will fatty acid synthesis take place in in liver cells?
In the cytoplasm and the mitochondria.
What are the 3 main enzymes or enzyme complexes that are involved in fatty acid synthesis?
Citrate lyase.
Carboxylase.
The fatty acid synthase complex.
What happens in step 1 of fatty acid synthesis?
ACoA is synthesised in the cytoplasm by converting citrate to ACoA and oxaloacetate.
Where is ACoA normally made?
In the mitochondria.
Why does ACoA need to be made in the cytoplasm for fatty acid synthesis?
Because ACoA cannot leave the mitochondria.
How is mitochondrial ACoA formed?
Citrate will leave the mitochondria and enter the cytoplasm where citrate lyase can break it down to ACoA and oxaloacetate.
When will citrate leave the mitochondria to enter the cytoplasm?
When levels of mitochondrial citrate are high.
How is mitochondrial citrate formed?
By combining ACoA and oxaloacetate with citrate lyase.
What happens in step 2 of fatty acid synthesis when ACoA is found in the cytoplasm
It can be used to form fatty acids.
How is ACoA used to form fatty acids in step 2 of fatty acid synthesis?
ACoA is carboxylated to malonyl-CoA by ACoA carboxylase.
What cofactor will ACoA carboxylase use?
Biotin.
What is the rate limiting step in fatty acid synthesis?
When ACoA is carboxylated to malonyl-CoA.
What happens to malonyl CoA once it has been synthesised in step 2 of fatty acid synthesis?
It can enter fatty acid synthase complex and be converted to palmitate.
What is the substrate for the fatty acid synthase complex?
Malonyl CoA.
What energy is used by the fatty acid synthase complex to convert malonyl CoA to palmitate?
2 NADPH molecules.
How many carbons will palmitate have?
16.
What is the only step of fatty acid synthesis that will take place in the mitochondria?
The formation of citrate.
What energy does ACoA carboxylase require to convert ACoA to malonyl CoA?
1 ATP.
How many carbons are added to ACoA when it is converted to malonyl CoA?
It increases by 1 carbon.
How many carbons does ACoA have?
2.
How many carbons does malonyl CoA have?
3.
What substrates are used by ACoA carboxylase?
ACoA + CO2.
The fatty acid synthase complex is composed of how many subunits?
2.
How many fatty acids are synthesised by the fatty acid synthase complex at the same time?
2.
How many enzymatic activities does each subunit of the fatty acid synthase complex have?
7.
What 2 components does each subunit of the fatty acid synthase complex have?
an acyl carrier protein domain (ACP).
A temporary holding domain with a cysteine residue.
Will the fatty acid synthase complex synthesise fatty acids with any double bonds in them?
No.
What kind of fatty acid synthesis is carried out at the fatty acid synthase complex?
FAS-1.
What is the 1st thing that happens at the fatty acid synthase complex?
The CO2 that was added by acyl CoA carboxylase is released to give an ACoA molecule.
What provides the energy needed for fatty acid synthesis in the fatty acid synthase complex?
The cleavage of the CO2 from malonyl CoA in step 1.
De novo fatty acid synthesis is based around what molecule?
An ACoA molecule.
What happens in step 2 of fatty acid synthesis in the fatty acid synthase complex?
The acetyl group of ACoA binds the ACP and is transferred to the SH of the cysteine residue in the holding domain.
Why is the ACoA moved to the holding domain in step 2?
To free up the ACP so it can grab another malonyl CoA.
What happens in step 3 of fatty acid synthesis in the fatty acid synthase complex?
ACoA’s are added to the ACoA in the holding domain until palmitate is formed.
What molecule provides the energy needed for FA synthase to function?
Malonyl CoA.
What molecule is formed when the 2 ACoA molecules are combined in step 3 of fatty acid synthesis in the fatty acid synthase complex?
A 3-keto acyl group.
How many carbons does the 3-keto acyl group formed in the fatty acid synthase complex have?
4.
What happens once palmitate is formed in the FA synthase complex?
It is activated in the ER to form palmitoyl CoA.
What enzyme activates palmitate in the ER?
Acyl CoA synthetase.
What can happen to palmitoyl CoA?
It can be elongated further, desaturated or esterified in the ER.
The FA synthase complex in the liver will always produce what kind of fatty acids?
Palmitate.
The FA synthase complex in the lactating mammary gland will always produce what kind of fatty acids?
Palmitate and medium chain fatty acids.
What are the benefits of using the FA synthase complex to synthesise fatty acids?
It allows for fast processing and prevents the release of short chain fatty acids.
What is the substrate for the FA synthase complex?
Malonyl CoA.
How does insulin affect the fatty acid synthase complex?
It induces enzyme complex formation and substrate availability.
What co-enzymes are used by the fatty acid synthase complex?
2 NADPH molecules per elongation of the chain.
Do bacteria use FAS-1 fatty acid synthesis?
No, they use FAS-2 synthesis and can add double bonds when the fatty acyl group is 10 carbons long.
What molecule will activate ACoA carboxylase?
Citrate.
What molecule will inhibit ACoA carboxylase?
Palmitoyl CoA.
What is the only cytoplasmic enzyme that can break down citrate to form ACoA and OAA.
Citrate lyase.
Why does citrate activate ACoA carboxylase?
Cytoplasmic citrate must be broken down quickly or it will inhibit the enzyme PFK-1
Why is it important that fatty acid synthesis does not inhibit glycolysis?
Because blood glucose levels are high.
What will lead to an up-regulation of ACoA carboxylase?
The presence of citrate in the cytoplasm.
What is palmitoyl CoA also known as?
Palmitate.
Why will palmitoyl CoA inhibit ACoA carboxylase?
To stop production of palmitate as it has detergent characteristics.
How are the detergent characteristics of palmitate usually bypassed?
It is immediately converted to palmitoyl CoA.
Why might palmitate build up in the cytoplasm?
Because the free CoA pool is limited and there may not be any available to form palmitoyl CoA.
What is the mode of inhibition by which an accumulation of palmitate in the cytoplasm will inhibit ACoA carboxylase known as?
Feedback inhibition.
When is ACoA carboxylase active?
When it is de-phosphorylated.
When is ACoA carboxylase inactive?
When it is phosphorylated.
What will lead to the de-phosphorylation of ACoA carboxylase?
Insulin will lead to the de-phosphorylation and activation of ACCase.
What hormone leads to the induction of ACoA carboxylase?
Insulin.
What will lead to the phosphorylation of ACoA carboxylase?
Glucagon and epinephrine via the CAMP system.
How do glucagon and epinephrine phosphorylate ACoA carboxylase?
They will use the CAMP system and phosphorylate AMP kinase kinase.
AMP kinase kinase will phosphorylate and activate AMP kinase.
AMP kinase will then phosphorylate and inhibit ACoA carboxylase.
What will allosterically activate AMP kinase?
AMP.
What will covalently activate AMP kinase?
Phosphorylation.
How will AMP activate AMP kinase?
High levels of AMP leads to the phosphorylation of ACCase by activating an AMP-dependent kinase.
The AMP-dependent kinase phosphorylate ACCase and inhibit it.
The presence of AMP will indicate that the body is in what state?
The fasting state.
What mode of FA synthesis regulation overrules all other forms of regulation?
The phosphorylation and inhibition of ACCase by AMP kinase.
