Fatty Acid Biosynthesis Flashcards
1
Q
Fatty acid biosynthesis
A
- Occurs in cytosol of liver
- Saturated FA’s of any required length can be generated
- ## Synthesis of unsaturated FA’s is limited, with some essential FA’s required from dietary sources
2
Q
Where does excess acetyl CoA go?
A
- Excess acetyl-CoA resulting from alcohol consumption and high sugar intake is shunted towards FA biosynthesis resulting in increased TAG production and storage
3
Q
Differences between FA biosynthesis and b-oxidation
A
B-oxidation: - occurs in mitochondrion - CoA is acyl group carrier - FAD is electron acceptor - L-B-hydroxyacyl group - NAD+ is electron acceptor - C2 unit product is acetyl CoA FA Biosynthesis - occurs in cytoplasm - ACP is acyl group carrier - NADPH is electron donor - d-B-hydroxyacyl group - NADPH is electron donor - C2 unit donor is malonyl CoA
4
Q
CoA vs Acyl carrier protein
A
- Both have cysteamine reactive group
- Both have pantetheinic acid linker
- ACP linked to hydroxal group of serine
- Co-A linked to phosphate of Adenosine monophosphate (AMP)
5
Q
Excess acetyl CoA in FA biosynthesis
A
- Excess acetyl-CoA is in mitochondria, but enzyme for FA synthesis is in cytosol
- Acetyl-CoA is transported out of mitochondria as citrate
- Citrate converted to oxaloacetate producing acetyl-CoA
- Subsequent conversion to pyruvate which returns to mitochondria, continuing the cycle
- This reaction facilitates conversion of NADH to NADPH
6
Q
Formation of malonyl CoA for FA synthesis
A
- Acetyl-CoA carboxylase enzyme converts Acetyl-CoA to Malonyl-CoA
- Biotin is required as co-enzyme
- Requires hydrolysis of ATP to produce a carboxybiotin intermediate
- Activated CO2 transferred to Acetyl-CoA to form Malonyl-CoA, converting 2C molecule to 3C
- Reaction is irreversible, and rate limiting step of FA synthesis
7
Q
Elongation cycle in FA synthesis
A
- Involves 7 enzymatic reactions in 6 steps
- Catalysed by Fatty acid synthase (Type I) enzyme system- composed of 2 identical polypeptides containing all 7 enzyme activities plus ACP
- End product is palmitic acid
8
Q
Step 1: Transfer of acetyl/malonyl from CoA to ACP
A
- Enzyme - Malonyl/acetyl-CoA-ACP transacylase
- Catalyses both transfer of acetyl and malonyl groups (same enzyme)
- Acetyl/Malonyl-CoA converted to Acetyl/Malonyl-ACP
- Require both acetyl-ACP and Malonyl-ACP to proceed
9
Q
Step 2: Condensation of acetyl-ACP & malonyl-ACP
A
- Enzyme - b-Ketoacyl-ACP synthase
- 2 stage reaction yielding acetoacetyl-ACP and CO2
- Stage 1 – loading of enzyme with acetyl group of acetyl ACP
- Stage 2 - coupling of acetyl group to the b-carbon of malonyl-ACP, Accompanied by loss of CO2, Decarboxylation drives formation of C-C bond
10
Q
Steps 3, 4 & 5: Sequential reduction,
dehydration, reduction
A
- Requires NADPH not NADH and FADH2
- Acetoacetyl ACP reduced (gains H) to D-b-hydroxybutyryl-ACP
- D-b-hydroxybutyryl-ACP dehydrated to a,b-trans-Butenoyl-ACP
- a,b-trans-Butenoyl-ACP reduced to Butyryl-ACP
- Butyryl-ACP – reattaches to b-Ketoacyl-ACP synthase
- Six more round to produce palmitoyl-ACP
11
Q
Step 6: hydrolysis of thioester bond between FA & ACP
A
- Enzyme - Palmitoyl thioesterase
- Requires H20
12
Q
Stoichiometry of 6 step reaction
A
- Acetyl-CoA + 7malonyl-CoA + 14 NADPH + 7H+ –>Palmitate + 8CoA + 7CO2 + 6H2O + 14 NADP+
13
Q
Stoichiometry when taking the account the initial carboxylation of acetyl-CoA (requiring hydrolysis of ATP) to synthesise malonyl-CoA
A
- 8Acetyl-CoA + 7ATP + 14 NADPH –> Palmitate + 8CoA + 7ADP + 7Pi + 6H2O + 14 NADP+
14
Q
Palmitic acid
A
- Precursor for saturated and unsaturated FAs
- Modification of palmitic acid catalysed by Elongases and Desaturases
15
Q
Elongation
A
- Can occur in ER and mitochondria
- In ER, elongation is similar to fatty acid synthesis i.e. addition of malonyl-CoA to acyl-CoA
- Requires NADPH and involves CoA derivatives not ACP derivatives
