D-lactate dehydrogenase, mitochondrial (LDHD)

D-lactate dehydrogenase, mitochondrial (LDHD) is a mitochondrial enzyme and flavoprotein that catalyzes the oxidation of D-lactate to pyruvate and plays a critical role in the catabolism of D-lactate and other D-2-hydroxyacids with hydrophobic moieties[1]. LDHD activity depends on FAD and Mn2+, and it is highly specific for D-enantiomers, with no activity towards L-lactate. Mutations in LDHD are associated with D-lactic acidosis—a rare disorder caused by excessive accumulation of D-lactate. The LDHD enzyme is structurally distinct from classical L-lactate dehydrogenases, possessing an FAD-binding domain, substrate-binding domain, and small C-terminal domain. Loss-of-function mutations in LDHD affect substrate binding and catalysis, which may underlie pathogenic metabolic phenotypes[1][2]. No clinically approved drugs directly target LDHD; however, its disease role suggests possible relevance in metabolic disorders.

Other names

Probable D-lactate dehydrogenase, mitochondrialLDHDDLDD-lactate dehydrogenaseDLACDprobable D-lactate dehydrogenase, mitochondrial

Oxidation of D-lactate (and other D-2-hydroxyacids with hydrophobic moieties) to pyruvate via a FAD and Mn2+-dependent catalytic mechanism[1]