Fatty Acid Synthesis Summary
Fatty Acid Synthesis
Overview
- Occurs in the cytoplasm of prokaryotes, adipocytes, and liver cells of eukaryotes.
- Utilizes Acetyl CoA from mitochondria, transported via citrate-malate shuttle.
- Palmitate (16:0) synthesis requires 8 acetyl CoA units; shortcut to calculate: (# C/2)
Biochemical Activity
- Acetyl CoA is condensed with bicarbonate to form malonyl CoA, catalyzed by acetyl CoA carboxylase I (ACC).
- This step is the committed step in fatty acid synthesis.
- Acyl group (malonate) is transferred to acyl carrier protein (ACP) by malonyl-CoA-ACP transacylase (MAT).
- ACP acts as a scaffold, with intermediates attached to the sulfhydryl end.
Fatty Acid Synthesis Steps
- Condensation: Malonyl ACP condenses with acetyl ACP, catalyzed by β-ketoacyl synthase, extending the chain by two carbons; produces acetoacetyl ACP and CO_2.
- Reduction: Carbonyl group reduced by 3-ketoacyl-ACP reductase, using NADPH as electron donor; converts keto to hydroxyl group, producing D-3-hydroxybutyryl ACP.
- Dehydration: D-3-hydroxybutyryl ACP dehydrated by β-hydroxyacyl ACP dehydratase, creating a trans double bond; product is crotonyl ACP and H_2O.
- Reduction: Double bond reduced by Enoyl ACP reductase, using NADPH, forming a single bond; product is butyryl ACP.
- The pathway extends the hydrocarbon chain two carbons at a time and repeats until palmitate (16:0) is synthesized.
Palmitate Production
- C16-acyl ACP is cleaved by palmitoyl-protein thioesterase (PPT), releasing palmitate (16:0).
Regulation of Acetyl CoA Carboxylase I (ACC)
- Covalent Modification: Insulin promotes dephosphorylation (activation), while glucagon and epinephrine promote phosphorylation (inactivation).
- Allosteric Regulation: Citrate (activator), Palmitoyl CoA (inhibitor)
Comparison with β-oxidation
| Feature | FA synthesis | FA metabolism |
|---|
| Location for Repeating Steps | Cytoplasm | Mitochondria |
| Carbon alteration | Condensation (step 1) | Thiolysis (step 4) |
| Rate-limiting Step | Yes with ACC | Yes with CAT1 |
| Coenzyme(s) Involved | NADPH | NAD^+ and FAD |
| Acyl Group Attached to | ACP | CoA |
Odd Chain Fatty Acids Synthesis
- Propionate (3 carbons) is transferred to ACP and condensed with malonyl-ACP, generating 3-oxovaleryl-ACP (5 carbons).
- Subsequent rounds add 2 carbons each.
Synthesis Beyond Palmitate (16C)
- Elongases in the endoplasmic reticulum are used for products with more than 16 carbons.
- Desaturases introduce cis double bonds; humans have Δ4-6 and 9 desaturases but lack methyl-end desaturases (ω3 and ω6).
Polyunsaturated Fatty Acids (PUFAs)
- Linolenic acid (ω3) and linoleic acid (ω6) are essential fatty acids. Humans cannot introduce double bonds beyond carbon-9.