Oxoglutarate dehydrogenase (E1 component) (OGDH)

Oxoglutarate dehydrogenase (E1 component, OGDH) is a mitochondrial enzyme and the first (E1) catalytic component of the 2-oxoglutarate dehydrogenase complex, a multi-subunit oxidoreductase crucial for the citric acid (TCA) cycle. OGDH catalyzes the thiamine-dependent decarboxylation of 2-oxoglutarate (alpha-ketoglutarate) to succinyl-CoA and CO2, with concomitant reduction of NAD+ to NADH. This reaction is essential for efficient cellular ATP production and for the maintenance of mitochondrial redox homeostasis. OGDH activity is tightly regulated allosterically and by its products (succinyl-CoA, NADH), ADP, and Ca2+. Dysfunction or inhibition of OGDH impedes mitochondrial metabolism and is implicated in neurodegenerative disorders, certain cancers, metabolic syndromes, and the aging process. Overactivation or impaired inhibition may contribute to oxidative damage via increased mitochondrial reactive oxygen species production. As a key metabolic control point with disease associations, OGDH is under evaluation as a therapeutic target, especially in oncology and neurology.

Other names

2-oxoglutarate dehydrogenase2-oxoglutarate dehydrogenase complex component E1OGDHE1oOGDC-E1OGDH-E1Alpha-KGDH-E1E1kOGDH2KGD1Alpha-ketoglutarate dehydrogenaseThiamine diphosphate (ThDP)-dependent 2-oxoglutarate dehydrogenaseAKGDHOGDCoxoglutarate (alpha-ketoglutarate) dehydrogenase (lipoamide)oxoglutarate decarboxylaseoxoglutarate dehydrogenase (succinyl-transferring)testicular tissue protein Li 131

Inhibition of OGDH reduces TCA cycle flux, lowering NADH and ATP production, potentially leading to cell death (anticancer effect, investigated with agents like CPI-613) Modulation of redox state and induction of oxidative stress through interference with NADH generation Inhibitors can cause energy deficiency and metabolic dysregulation in non-target tissues