What is the biochemical pathway for fatty acid synthesis starting from acetyl-CoA?

Fatty acid synthesis starts with acetyl-CoA, which is converted to malonyl-CoA through the action of acetyl-CoA carboxylase. Malonyl-CoA is then used in a series of reactions catalyzed by fatty acid synthase to elongate the fatty acid chain. This process involves the repeated addition of two-carbon units from malonyl-CoA to the growing fatty acid chain, with the release of CO2 in each step. The final product of fatty acid synthesis is a long-chain fatty acid, typically palmitic acid (C16:0).

Fatty Acid Synthesis Pathway

Step 1: Formation of Malonyl-CoA

- Acetyl-CoA + HCO3- → Malonyl-CoA (by acetyl-CoA carboxylase)

Step 2: Acyl Carrier Protein (ACP) Priming

- Acetyl-CoA + ACP → Acetyl-ACP (by acetyltransferase)

Step 3: Initiation

- Malonyl-ACP + Acetyl-ACP + Enzyme → Ketoacyl-ACP (by β-ketoacyl-ACP synthase I)

Step 4: Reduction

- Ketoacyl-ACP + NADPH + H+ → Hydroxyacyl-ACP (by β-ketoacyl-ACP reductase)

Step 5: Dehydration

- Hydroxyacyl-ACP → Enoyl-ACP (by β-hydroxyacyl-ACP dehydratase)

Step 6: Reduction (Repeat)

- Enoyl-ACP + NADH + H+ → Acyl-ACP (by β-enoyl-ACP reductase)

Step 7: Chain Elongation (Repeat)

- Acyl-ACP + Malonyl-ACP + Enzyme → Ketoacyl-ACP (by β-ketoacyl-ACP synthase I)
- Steps 4-6 are repeated, extending the fatty acid chain by two carbons per cycle.

Step 8: Termination

- When the desired chain length is reached, a thioesterase enzyme hydrolyzes the acyl-ACP, releasing the free fatty acid.

Additional Notes:

- The enzyme complex responsible for fatty acid synthesis is called fatty acid synthase (FAS).
- The initiation step uses acetyl-CoA as the starter unit, but subsequent elongation cycles use malonyl-CoA.
- The synthesis occurs in the cytoplasm of cells.
- The products of fatty acid synthesis can be used for energy storage (triacylglycerols) or membrane synthesis (phospholipids).