8 fatty acid synthesis
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95 Terms
What is fatty acid synthesis?
The anabolic pathway that synthesises fatty acids from acetyl CoA.
Is fatty acid synthesis simply the reverse of β-oxidation?
No, it uses different enzymes, locations, carriers, and cofactors.
Where does fatty acid synthesis occur in mammals?
Cytosol.
Where does β-oxidation occur?
Mitochondria.
What carrier is used in fatty acid synthesis?
Acyl carrier protein (ACP).
What carrier is used in fatty acid oxidation?
Coenzyme A.
What reducing cofactor is used in fatty acid synthesis?
NADPH.
What reducing cofactors are produced in fatty acid oxidation?
NADH and FADH₂.
Why are synthesis and oxidation separated?
Allows independent regulation and prevents futile cycling.
What is the committed step of fatty acid synthesis?
Formation of malonyl CoA.
What enzyme catalyses the committed step?
Acetyl CoA carboxylase (ACC).
Reaction catalysed by ACC?
Acetyl CoA + CO₂ + ATP → malonyl CoA.
Why is ACC the committed step?
It is irreversible and commits acetyl CoA to fatty acid synthesis.
What vitamin cofactor does ACC require?
Biotin (vitamin B7).
Role of biotin in ACC?
Carries activated CO₂.
Why does ACC require ATP?
To drive carboxylation.
What is malonyl CoA?
The activated 2-carbon donor for fatty acid elongation.
What happens to malonyl CoA before synthesis?
It is transferred to ACP to form malonyl-ACP.
What is fatty acid synthase?
A multi-enzyme complex catalysing fatty acid synthesis.
How is mammalian fatty acid synthase organised?
A dimer of identical multifunctional polypeptides.
How many enzyme activities are in fatty acid synthase?
Seven.
How are bacterial fatty acid synthesis enzymes organised?
As separate enzymes.
What is the swinging arm mechanism?
ACP moves the growing fatty acid between active sites.
What molecule forms ACP’s swinging arm?
4′-phosphopantetheine.
Why is the swinging arm efficient?
Rapid substrate transfer between catalytic sites.
First condensation reaction in fatty acid synthesis?
Acetyl-ACP + malonyl-ACP → acetoacetyl-ACP.
What happens during condensation?
CO₂ is released.
Why is CO₂ release important?
Drives condensation forward.
What happens after condensation?
Reduction, dehydration, reduction.
What is the first reduction cofactor?
NADPH.
What intermediate forms after first reduction?
D-3-hydroxybutyryl-ACP.
What happens during dehydration?
Water is removed to form an unsaturated intermediate.
Final product after second reduction in first cycle?
Butyryl-ACP.
How many carbons are added per synthesis cycle?
2 carbons.
Why are 2 carbons added each cycle?
Malonyl CoA contributes 2 carbons after decarboxylation.
What is the main end product of mammalian fatty acid synthase?
Palmitate (C16:0).
How many acetyl CoA are needed for palmitate synthesis?
8 acetyl CoA.
How many ATP are needed for palmitate synthesis?
7 ATP.
How many NADPH are needed for palmitate synthesis?
14 NADPH.
Why are only 7 ATP needed if 8 acetyl CoA are used?
Only 7 acetyl CoA are converted into malonyl CoA.
What is palmitate?
A 16-carbon saturated fatty acid.
How does acetyl CoA reach the cytosol?
Via the citrate shuttle.
Why can’t acetyl CoA cross the mitochondrial membrane directly?
The inner membrane is impermeable to acetyl CoA.
How does the citrate shuttle work?
Acetyl CoA combines with oxaloacetate to form citrate, which is exported.
What happens to citrate in the cytosol?
It is cleaved to regenerate acetyl CoA.
How does the citrate shuttle help fatty acid synthesis?
Supplies cytosolic acetyl CoA and helps generate NADPH.
What enzyme generates NADPH in the citrate shuttle?
Malic enzyme.
Why is high NADPH/NADP+ ratio important?
Favours reductive biosynthesis.
Where does fatty acid synthesis occur in plants?
Chloroplasts.
Why in chloroplasts?
NADPH is generated by photosynthesis.
When is fatty acid synthesis most active?
When carbohydrate is abundant and fatty acids are low.
What hormone stimulates fatty acid synthesis?
Insulin.
Why does insulin stimulate fatty acid synthesis?
Promotes glucose uptake and anabolic metabolism.
How does glucose contribute to fat synthesis?
Converted to acetyl CoA.
What activates acetyl CoA carboxylase allosterically?
Citrate.
Why does citrate activate ACC?
Signals abundant energy/building blocks.
How does citrate activate ACC?
Promotes polymerisation.
What inhibits acetyl CoA carboxylase?
Palmitoyl CoA.
Why does palmitoyl CoA inhibit ACC?
End-product feedback inhibition.
How does palmitoyl CoA inhibit ACC?
Prevents polymerisation.
What inhibits ACC by covalent regulation?
AMP-activated protein kinase (AMPK).
Why does AMPK inhibit ACC?
Low energy state.
What hormone inhibits fatty acid synthesis?
Glucagon.
How does glucagon inhibit ACC?
Promotes phosphorylation.
Why is fatty acid synthesis low during fasting?
Glucagon high, energy conservation favoured.
What happens after palmitate synthesis?
Elongation and desaturation.
Where does fatty acid elongation occur?
Endoplasmic reticulum.
What donor is used in elongation?
Malonyl CoA.
How many carbons are added during elongation?
2 carbons.
What is stearic acid?
C18:0 saturated fatty acid.
What is desaturation?
Addition of double bonds.
Where does desaturation occur?
Endoplasmic reticulum.
Example desaturation reaction?
Stearoyl CoA → oleoyl CoA.
What is oleic acid?
C18:1 monounsaturated fatty acid.
What enzyme performs desaturation?
Fatty acyl CoA desaturase.
What cofactor is used in desaturation?
NADH.
Why are some fatty acids essential?
Humans cannot introduce double bonds beyond carbon 9.
Name the essential fatty acids.
Linoleic acid and α-linolenic acid.
Why must essential fatty acids come from diet?
Humans lack appropriate desaturases.
What is arachidonic acid?
A polyunsaturated fatty acid derived from linoleic acid.
Why is arachidonic acid important?
Precursor of prostaglandins and leukotrienes.
What is triacylglycerol synthesis?
Formation of fat storage molecules from glycerol + fatty acids.
Where does triacylglycerol synthesis occur?
Endoplasmic reticulum.
Main tissues for triacylglycerol synthesis?
Liver and adipose tissue.
What provides the glycerol backbone?
Glucose metabolism intermediates.
What provides fatty acids for triacylglycerol synthesis?
Fatty acyl CoA.
When is triacylglycerol synthesis favoured?
Anabolic/fed state.
Hormonal state favouring TAG synthesis?
High insulin, low glucagon/adrenaline.
Why is triacylglycerol breakdown low in fed state?
Low glucagon/adrenaline.
Does liver store large TAG reserves?
No.
How does liver export newly synthesised fat?
As VLDL.
What is VLDL?
Very low-density lipoprotein carrying endogenous TAG.
What is the main membrane phospholipid?
Phosphatidylcholine.
Why is phosphatidylcholine important?
Major membrane structural lipid.
Overall metabolic purpose of fatty acid synthesis?
Long-term energy storage and lipid biosynthesis.