The first iteration of the sequence catalyzed by this enzyme can be
represented by the seven following reactions.
- In the first reaction acetyl CoA is added to a cysteine -SH
group of the condensing enzyme (CE) domain:
acetyl CoA + CE-cys-SH -> acetyl-cys-CE + CoASH
Mechanistically this is a two step process, in which the
group is first transferred to the ACP (acyl carrier
peptide), and then to the cysteine -SH group of the condensing enzyme domain.
- In the second reaction malonyl CoA is added to the ACP
sulfhydryl group:
malonyl CoA + ACP-SH -> malonyl ACP + CoASH
This -SH group is part of a phosphopantethenic acid
prosthetic group of the ACP.
- In the third reaction the acetyl group is transferred to the
malonyl group with the release of carbon dioxide:
malonyl ACP + acetyl-cys-CE -> beta-ketobutyryl-ACP +
CO2
- In the fourth reaction the keto group is reduced to a hydroxyl
group by the beta-ketoacyl reductase activity:
beta-ketobutyryl-ACP + NADPH + H+ ->
beta-hydroxybutyryl-ACP + NAD+
- In the fifth reaction the beta-hydroxybutyryl-ACP is
dehydrated to form a trans- monounsaturated fatty acyl group
by the beta-hydroxyacyl dehydratase activity:
beta-hydroxybutyryl-ACP -> 2-butenoyl-ACP + H2O
- In the sixth reaction the double bond is reduced by NADPH,
yielding a saturated fatty acyl group two carbons longer than
the initial one (an acetyl group was converted to a butyryl
group in this case):
2-butenoyl-ACP + NADPH + H+ -> butyryl-ACP +
NADP+
The butyryl group is then transferred from the ACP
sulfhydryl group to the CE sulfhydryl:
butyryl-ACP + CE-cys-SH -> ACP-SH + butyryl-cys-CE
This is catalyzed by the same transferase activity as
was used previously for the original acetyl group.
The butyryl group is now ready to condense with a new
malonyl group (third reaction above) to repeat the
process.
- When the fatty acyl group becomes 16 carbons long, a
thioesterase activity hydrolyses it, forming free palmitate:
palmitoyl-ACP + H2O -> palmitate + ACP-SH