There are two previous reports of malonyl-and methylmalonyl-aza(dethia)CoA synthesis and use in enzyme assays. In both cases the material was tested for the ability to undergo decarboxylative Claisen condensation or decarboxylative Michael addition. Minor enzymatic activity with the malonyl-oxa(dethia)CoA analog has been reported, while we here demonstrate again that the malonyl-aza(dethia)CoA is stable in the presence of an enzyme. The β-keto acid decarboxylation would normally be enabled by the formation of an enolate intermediate, however amide resonance competes with enolate formation. The malonyl-oxa(dethia)CoA analog also likely behaves similar to the amide analog with regard to ester resonance competing with enolate formation. For example, if we consider the methylgroup pKa of acetyl-CoA and analogs (pKa ~21 for the thioester, ~26 for the ester and ~28 for the amide), it is easiest to deprotonate the methyl-group of acetyl-thioester, then the acetyl-ester and hardest to deprotonate the acetyl-amide. Decarboxylation to generate the same enolate as deprototonation of the methyl-group is expected to follow a similar pattern. Stabilization of the enolate during malonyl-CoA analog decarboxylation by FabH is appropriately 5 orders of magnitude more difficult for the ester and 7 for the amide compared to the thioester. This phenomena reveals why the analogs are stable and likely promising isosteres for structure-function studies in experiments that take hours to days including NMR and crystallography.