Myotonic muscular dystrophy (neonatal)
Jun. 02, 2023
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The mitochondrial enzyme D-2 hydroxyglutarate dehydrogenase catalyzes the irreversible oxidation of D-2-hydroxyglutarate; inactivation of this enzyme by mutations causes D-2-hydroxyglutaric aciduria type I. D-2-hydroxyglutarate can be produced from alpha-ketoglutarate by four different enzymes. Hydroxyacid-oxoacid transhydrogenase (HOT) oxidizes 4-hydroxybutyrate using alpha-ketoglutarate as an electron acceptor. 3-P- glycerate dehydrogenase, an enzyme involved in the serine synthesis pathway (not shown), has side activity on alpha-ketoglutarate due to the structural similarity of alpha-ketoglutarate with the normal product of this enzyme (ie, 3-phosphohydroxypyruvate). Mutated forms of IDH2 in D-2-hydroxyglutaric aciduria type II and mutated forms of IDH1 and IDH2 in glioblastomas and various other cancers efficiently catalyze the reduction of alpha-ketoglutarate to D-2-hydroxyglutarate; in this situation, the metabolic capacity of D-2-hydroxyglutarate dehydrogenase is exceeded, and D-2-hydroxyglutarate accumulates. (Source: Veiga-da-Cunha M, Van Schaftingen E, Bommer GT. Inborn errors of metabolite repair. J Inherit Metab Dis 2020;43:14-24. Creative Commons Attribution License.)