Synthesis of Palmitate from Acetyl-CoA

Fatty acid biosynthesis from acetyl-CoA to palmitate involves an enzyme complex called fatty acid synthase, which appears to operate by a swinging arm mechanism involving the growing fatty acyl group linked to acyl carrier protein (Figure 18.29). Each of the individual enyzmatic activities below is a part of the fatty acid synthase complex.

The first step in the synthesis of palmitate is the synthesis of malonyl-CoA from acetyl-CoA and HCO 3- (Figure 18.24). This reaction requires ATP and is catalyzed by acetyl-CoA carboxylase. It is the point of regulation of the pathway. The active form of acetyl-CoA carboxylase is a long filamentous array of monomer units. The individual monomers are generally inactive. The malonyl-CoA produced in this reaction, along with acetyl-CoA, provide substrates for the fatty acid synthase complex. The various enzymatic activities of the fatty acid synthase complex are summarized as follows (Figure 18.27).

> 1. Acetyl-CoA + ACP <=> Acetyl-ACP + CoASH (catalyzed by Acetyl-CoA-ACP Transacylase)

> 2. Malonyl-CoA + ACP <=> Malonyl-ACP + CoASH (catalyzed by Malonyl-CoA-ACP Transacylase

> 3. Acetyl-ACP + Malonyl-ACP <=> -Ketoacyl-ACP + ACP + CO 2 (catalyzed by -Ketoacyl-ACP Synthase)

> 4. -Ketoacyl-ACP + NADPH + H+ <=> D-3-Hydroxyacyl-ACP + NADP+ (catalyzed by -ketoacyl-ACP reductase)

> 5. D-3-Hydroxyacyl-ACP <=> Trans-2-enoyl-ACP + H 2O (catalyzed by 3-Hydroxylacyl-ACP Dehydrogenase)

> 6. Trans-2-enoyl-ACP + NADPH + H+ <=> Acyl-ACP + NADP+ (catalyzed by Enoyl-ACP Reductase)

Starting with acetyl-CoA, the process cycles between steps 1-6 seven times to yield palmitoyl-ACP, which is hydrolyzed to give palmitate and ACP. Note that the CO 2, which was added to acetyl-CoA in the acetyl-CoA carboxylase-catalyzed step, is removed subsequently and not incorporated into the final product.

See also: Fatty Acid Biosynthesis Strategy, Figure 18.23, Figure 18.24, Fatty Acid Synthase

INTERNET LINK: Fatty Acid Biosynthesis