Hexanoyl-ACP

The first step in de novo fatty acid synthesis is the production of malonyl-CoA from acetyl-CoA and bicarbonate. This committed step is catalyzed by acetyl-CoA carboxylase present in the cytoplasm of liver cells and adipocytes. After replacement of the CoA residue in acetyl-CoA by ACP (acyl carrier protein), malonyl-ACP is used to convert acetyl-ACP to butyryl-ACP by the fatty acid synthase complex. In this multistep reaction, NADPH is used as donor of hydrogen atoms and CO2 is produced. Butyryl-ACP is subsequently elongated to hexanoyl-ACP by a similar process in which malonyl-ACP serves as donor of two carbon atoms required for lengthening of the growing acyl chain. This process is repeated until palmitic acid... 

Transfer of an acyl group between the first and second domains is reversible, which allows butanoyl ACP to return to the first domain of mFAS where it reacts with a second malonyl-ACP. The resulting six-carbon P-keto thioester then proceeds through another reduction— dehydration—reduction sequence to give hexanoyl-ACP. 

Figure 1. Influence of acyl-ACPs on the activity of KAS III in Cuphea lanceolata seed extract. A, Activity of KAS III in the presence 0 pM ( ), 0.2 pM (, 0.5 pM (O), 1.0 pM and 2.0 pM (O) acyl-ACPs B, Elongation products of KAS III reaction using 10 pM acetyl-CoA (1), supplied with 10 pM butyryl-ACP (2), hexanoyl-ACP (3), octanoyl-ACP (4) and decanoyl-ACP (5). Bars represent elongation (%) of acetyl-CoA ( ) and acyl-ACPs (JM).

Polyketide formation in AF biosynthesis utilizes a hexanoyl CoA starter unit that is synthesized by aid of two specialized FASs (39) (Figure 4A). The genes for these FASs are transcribed from a common promoter region (40). The alpha subunit FAS has separate ACP and PP domains as well as KS and KR domains while the beta subunit has KS, AT, ACP and thioesterase (TE) domains (41). 

Butyroyl-S-ACP now reacts with a second molecule of malonyl-S-ACP and proceeds through reactions 3-6 to form hexanoyl-S-ACP, etc., until palmitoyl-S-ACP is formed. 

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