The pH rate profile of FabH C112Q and even wild-type with respect to malonyl-CoA decarboxylation is puzzling. At pH 6 FabH C112Q displays a lag phase for the decarboxylation of malonyl-CoA and a dramatically reduced rate, Supplemental Figure . In one proposed mechanism for decarboxylation, the active site histidine and asparagine form hydrogen bonds with the substrate malonyl-thioester ketone. In the proposed mechanism where the histidine plays a role in enolate stabilization, the active site histidine is in a neutral state. One explanation for abolished decarboxylation activity in the absence of acetyl-CoA at pH 6 is that the histidine becomes protonated and changes conformation. How is it that the wild-type enzyme remains active at pH 6 with both substrates, while malonyl-CoA alone is not acted upon? Is the lack of decarboxylation by FabH C112Q at pH 6 due to the enzyme adopting the non-catalytic state?