Dimethylglycine dehydrogenase, mitochondrial (DMGDH)

Dimethylglycine dehydrogenase, mitochondrial (DMGDH) is a FAD- and tetrahydrofolate-dependent enzyme located in the mitochondrial matrix that catalyzes the oxidative demethylation of N,N-dimethylglycine to sarcosine, a key step in the pathway of choline degradation and one-carbon metabolism[1][3][4][7]. The enzyme also participates in electron transfer to the mitochondrial respiratory chain and helps prevent the cellular accumulation of toxic formaldehyde by transferring methyl groups to tetrahydrofolate, forming 5,10-methylenetetrahydrofolate[3][5][7]. Genetic mutations in DMGDH can cause dimethylglycine dehydrogenase deficiency, a rare metabolic disorder marked by increased dimethylglycine in blood and urine, sometimes accompanied by a characteristic fish-like body odor[4][7]. DMGDH operates as a monomer and requires a covalently bound FAD cofactor and noncovalently bound tetrahydrofolate for its enzymatic activity[3][4][7]. There are currently no well-established direct drug modulators or approved therapies targeting DMGDH.

Other names

N,N-dimethylglycine dehydrogenaseDimethylglycine dehydrogenaseN,N-dimethylglycine oxidaseMe2GlyDHN,N-dimethylglycine:electron-transfer flavoprotein oxidoreductase (demethylating)N,N-dimethylglycine:(acceptor) oxidoreductase (demethylating)