Methylmalonate-semialdehyde dehydrogenase (acylating), mitochondrial (MMSDH)

Methylmalonate-semialdehyde dehydrogenase (acylating), mitochondrial (MMSDH), encoded by the ALDH6A1 gene, is a mitochondrial enzyme of the aldehyde dehydrogenase superfamily[5][4]. It catalyzes the NAD^+-dependent irreversible oxidative decarboxylation of malonate semialdehyde and methylmalonate semialdehyde to yield acetyl-CoA and propionyl-CoA, respectively[1][7][4]. This activity is essential for the breakdown of valine and pyrimidines, playing a critical role in intermediary metabolism and energy production[3][4][5][9]. Genetic deficiency in MMSDH leads to a rare metabolic disorder characterized biochemically by elevated beta-alanine and 3-hydroxypropionic acid, with potential clinical consequences[9][3][5]. The enzyme is unique among aldehyde dehydrogenases because it requires coenzyme A for catalysis, producing CoA esters rather than carboxylate ions as products[1][2]. There are currently no therapeutic drugs known to directly target or modulate MMSDH for clinical use.

Other names

MMSA dehydrogenaseMMSDHMethylmalonic-semialdehyde dehydrogenase (acylating)Aldehyde dehydrogenase 6 family member A1ALDH6A1Malonate-semialdehyde dehydrogenase (acylating)