Principles of Biochemistry Volume 2 - A. Lehninger 1985

Bioenergetics and Metabolism
Lipid Biosynthesis
The sulfhydryl groups of fatty acid synthase initially interact with acyl groups.

The elongation of a fatty acid chain can begin only after both sulfhydryl groups are "loaded" with their respective acyl groups. This occurs via two sequential enzymatic reactions (Fig. 21-8). In the first reaction, catalyzed by ACP-acetyltransferase, the acetyl group of acetyl-S-CoA is transferred to the —SH group of the synthase Cysteine residue (denoted by the letter E):

In the second reaction, the malonyl group of malonyl-S-CoA is transferred to the phosphopantetheine sulfhydryl group of ACP. This reaction is catalyzed by

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Fig. 21-8. Loading of the synthase with acetyl and malonyl groups; the first is linked to the —SH group of cysteine (Cys), and the second to the —SH group of 4'-phosphopantetheine (Pp). Incoming malonyl groups always attach to the phosphopantetheine SH groups.

The net result of these two reactions is that two acyl groups become covalently attached to the synthase: an acetyl group (linked to the —SH group of cysteine) and a malonyl group (linked to the —SH group of phosphopantetheine). These two acyl groups are positioned quite close to each other within the enzyme molecule. The synthase is now ready for the fatty acid chain elongation process. It is important to remember that the malonyl group binds exclusively to the —SH group of pantetheine.