chain elongation. Now in the KS domain, the bound acyl group is condensed with the malonate to form 3-ketoacyl intermediate: β-ketobutyryl-ACP, releasing carbon dioxide in the process. 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 3-Hydroxyacyl ACP dehydrase (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. Termination Once the fatty acid chain reaches 16 or 18 carbons long after cycles of elongation, termination occurs. In the final round of elongation, rather than being taken back to the KS domain, the fatty acid product, which is still bound to ACP, is taken from the ER domain to the MPT domain. Here, CoA is attached to the fatty acid, and the resulting long chain fatty acyl-CoA is released into the cytosol. Applications Fatty acids are key components of a cell, therefore, the regulation or inhibition of fatty acid synthesis hold severe consequences for cellular function. The malfunction of the fatty acid synthesis pathway can result in cancer and obesity. However, the significance of fatty acid synthesis also make the fatty acid synthesis pathway a potential target for the search and study of anticancer and antibiotic drugs. It has been found that in humans, fatty acid synthase, is overly expressed in cancer cells. Therefore, FAS, which has been associated only with energy production prior, is now associated with aggressive tumor growth and survival. Studies have also found that human fatty acid synthase is overly expressed in prostate cancer cells. References Further reading EC 2.3.1 NADPH-dependent enzymes NADH-dependent enzymes Enzymes of known structure