Aldehyde dehydrogenase acyl enzyme intermediate

The best-studied example of a CoA-dependent nonphosphorylating ALDH is the methylmalonate-semi-aldehyde dehydrogenase, which has been isolated from both mammalian and bacterial sources. This enzyme transforms malonate semialdehyde and methylmalonate semialdehyde into acetyl-CoA and propionyl-CoA, respectively, through an oxidation reaction as described above, followed by a decarboxylation reminiscent of other (3-keto acids. Mechanistic studies of the B. sukilis enzyme have shown that it is activated by NAD" " binding, that it exhibits half-of-sites reactivity (only two moles of NADH forms per tetrameric protein unit) and that the decarboxylation reaction occurs after formation of the acyl-enzyme intermediate. Acyl transfer from the enzyme to CoA completes the reaction. 

The early SWSF studies of this enzyme indicated that the reaction occurs via a chemical intermediate. Due to the apparent similarity of the chemistry catalyzed by D-glyceraldehyde-3-phosphate dehydrogenase (GPDH) and by aldehyde dehydrogenase, it was speculated that the chemical intermediate formed in this reaction might be an acyl-enzyme (viz., Equation 3) analogous to the GPDH acylenzyme intermediate... 

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