Oxoglutarate dehydrogenase (OGDH) (OGDH)

Oxoglutarate dehydrogenase (OGDH) is the E1 component of the 2-oxoglutarate dehydrogenase complex (OGDHC), a key rate-limiting enzyme in the tricarboxylic acid (TCA) cycle (UniProt Q02218). It catalyzes the oxidative decarboxylation of alpha-ketoglutarate to succinyl-CoA, producing NADH for the electron transport chain (NIH, PMID: 35272141). Beyond its mitochondrial role, OGDH can localize to the nucleus to facilitate histone succinylation, thereby regulating gene expression and cellular differentiation (NIH, PMID: 29211711). In many cancers, such as acute myeloid leukemia and pancreatic cancer, OGDH is essential for maintaining metabolic flux and supporting rapid proliferation (NIH, PMID: 39675585). Therapeutic strategies, notably the drug Devimistat (CPI-613), target OGDH to disrupt tumor energetics and induce apoptosis (Cornerstone Pharmaceuticals). However, genetic mutations in OGDH lead to severe neurodevelopmental disorders characterized by metabolic acidosis and developmental delay (NIH, PMID: 35272141). Furthermore, reduced OGDH activity is a hallmark of neurodegenerative conditions like Alzheimer's disease, where it contributes to impaired bioenergetics and oxidative stress (Wikipedia).

Other names

Alpha-ketoglutarate dehydrogenase2-oxoglutarate dehydrogenaseOGDC-E1KGD1E1kE1o2-oxoglutarate dehydrogenase complex component E1

Devimistat (CPI-613) acts as a lipoate analog that selectively inhibits the E1 subunit of the 2-oxoglutarate dehydrogenase complex and the pyruvate dehydrogenase complex in tumor cells, leading to the disruption of mitochondrial metabolism, depletion of ATP, and induction of apoptosis (Cornerstone Pharmaceuticals; NIH, PMID: 39675585).