In enzymology, methylmalonate-semialdehyde dehydrogenase (acylating) () is an enzyme that catalyzes the chemical reaction
The three substrates of this enzyme are methylmalonic acid semialdehyde, coenzyme A (CoA), and oxidised nicotinamide adenine dinucleotide (NAD<sup>+</sup>). Its products are propionyl-CoA, carbon dioxide, reduced NADH, and a proton.
This enzyme belongs to the family of oxidoreductases, specifically those acting on the aldehyde or oxo group of donor with NAD+ or NADP+ as acceptor. The systematic name of this enzyme class is 2-methyl-3-oxopropanoate:NAD+ 3-oxidoreductase (CoA-propanoylating). Other names in common use include MSDH, and MMSA dehydrogenase. This enzyme participates in 3 metabolic pathways: inositol metabolism, valine, leucine and isoleucine degradation, and propanoate metabolism.
As of late 2007, only one structure has been solved for this class of enzymes, with the PDB accession code .