Biosynthesis of Fatty Acids and Eicosanoids:-The Fatty Acid Synthase Reactions Are Repeated to Form Palmitate
Production of the four-carbon, saturated fatty acyl–ACP completes one pass through the fatty acid synthase complex. The butyryl group is now transferred from the phosphopantetheine OSH group of ACP to the Cys -SH group of -ketoacyl-ACP synthase, which initially bore the acetyl group (Fig. 21–5). To start the next cycle of four reactions that lengthens the chain by two more car bons, another malonyl group is linked to the now unoccupied phosphopantetheine OSH group of ACP (Fig. 21–6). Condensation occurs as the butyryl group, acting like the acetyl group in the first cycle, is linked to two carbons of the malonyl-ACP group with concurrent loss of CO2. The product of this condensation is a six carbonacyl group, covalently bound to the phospho pantetheine OSH group. Its -keto group is reduced in the next three steps of the synthase cycle to yield the saturated acyl group, exactly as in the first round of re actions—in this case forming the six-carbon product. Seven cycles of condensation and reduction produce the 16-carbon saturated palmitoyl group, still bound to ACP. For reasons not well understood, chain elongation by the synthase complex generally stops at this point and free palmitate is released from the ACP by a hydrolytic activity in the complex. Small amounts of longer fatty acids such as stearate (18:0) are also formed. In certain plants (coconut and palm, for example) chain termination occurs earlier; up to 90% of the fatty acids in the oils of these plants are between 8 and 14 carbons long. We can consider the overall reaction for the syn thesis of palmitate from acetyl-CoA in two parts. First, the formation of seven malonyl-CoA molecules:
7 Acetyl-CoA+7CO2+7ATP→ 7 malonyl-CoA+7ADP+ 7Pi (21–1)
then seven cycles of condensation and reduction:
Acetyl-CoA+7 malonyl – CoA + 14NADPH +14H → palmitate+7CO2+8 CoA+14NADP++ 6H2O (21–2)
The overall process (the sum of Eqns 21–1 and 21–2) is 8 Acetyl-CoA +7ATP +14NADPH +14H+→palmitate +8 CoA+7ADP +7Pi +14NADP + 6H2O (21–3)
FIGURE 21–6 Beginning of the second round of the fatty acid synthesis cycle. The butyryl group is on the Cys OSH group. The incoming malonyl group is first attached to the phosphopantetheine OSH group. Then, in the condensation step, the entire butyryl group on the Cys -SH is exchanged for the carboxyl group of the malonyl residue, which is lost as CO2 (green). This step is analogous to step 1 in Fig ure 21–5. The product, a six-carbon -ketoacyl group, now contains four carbons derived from malonyl-CoA and two derived from the acetyl-CoA that started the reaction. The -ketoacyl group then undergoes steps 2 through 4, as in Figure 21–5.
