Expansion
Cytoplasmic synthesis from acetyl-CoA using NADPH, with acetyl-CoA carboxylase rate limiting
Expansion
| Feature | Synthesis | Oxidation |
|---|---|---|
| Location | Cytoplasm | Mitochondrion |
| Cofactor | NADPH | Produces NADH and FADH2 |
| Carrier | Acyl carrier protein | Coenzyme A |
| Key enzyme | Acetyl-CoA carboxylase | Carnitine palmitoyltransferase 1 |
| Stimulated by | Insulin, citrate | Glucagon, adrenaline |
Steps
- Acetyl-CoA is exported from the mitochondrion as citrate (the citrate shuttle), since acetyl-CoA itself cannot cross
- Acetyl-CoA carboxylase (requiring biotin) makes malonyl-CoA: the rate-limiting and committed step
- Fatty acid synthase adds two carbons per cycle, using NADPH, producing palmitate (16 carbons)
- Elongation and desaturation follow
The elegant control point is malonyl-CoA, which inhibits CPT1 and therefore blocks fatty acid entry into the mitochondrion. This prevents simultaneous synthesis and oxidation, a futile cycle.
NADPH comes chiefly from the pentose phosphate pathway and the malic enzyme, which links the two pathways.