Fatty-acyl-Co A Synthase - Mechanism - Elongation

Elongation

Elongation involves four main reactions:

1. The acetyl unit on ACP is condensed with malonyl-ACP to form β-ketobutyryl-ACP
2. Ketobutyryl-ACP is then reduced by ketoacyl-ACP reductase to afford β-hydroxyacyl-ACP
3. β-hydroxyacyl-ACP is then dehydrated to produce enoyl-ACP
4. Enoyl-ACP is then reduced by enoyl reductase (ER) to form a saturated acyl-ACP, which can be elongated again in a new cycle of elongation

Elongation itself occurs in mainly in the α subunit, though the entire process required for elongation is a coordinated system which involves the α and β subunits. ACP first delivers the acetate group, which had been attached during priming, to the ketoacyl synthase (KS) domain in the α subunit (Figure 1A, reaction 3). ACP then moves back to the β subunit to the malonyl transacylase (MPT) domain and binds to a malonyl of malonyl-CoA, which will be used for elongation. The newly bound malonyl-ACP then swings back to the KS domain and transfers the malonate group for chain elongation. Now in the KS domain, the bound acyl group is condensed with the malonate to form 3-ketoacyl intermediate: β-ketobutyryl-ACP.

In the α subunit is also the ketoacyl reductase (KR) domain. The KR domain is NADPH dependent, and catalyzes substrate reduction, in which ketobutyryl-ACP is reduced to β-hydroxyacyl-ACP by NADPH.

The β-hydroxyacyl-ACP is then transferred back to the β subunit, where it is dehydrated in dehydratase (DH) domain. Another reduction reaction then performed in the enoyl reductase (ER) domain of the β subunit to form a saturated acyl-ACP chain. Finally, ACP brings the substrate back to the KS domain of the α subunit for another cycle of elongation. The elongation cycle is often repeated 3 more times before termination.

Notice the unique characteristic of ACP, which is vital to fatty acid synthesis in its role of shuttling the reaction intermediates between the α and β subunits’ catalytic domains.