2-oxoglutarate dehydrogenase (mitochondrial) (OGDH)

The Alpha-ketoglutarate dehydrogenase complex E1 component, commonly known as 2-oxoglutarate dehydrogenase (OGDH), is a rate-limiting enzyme within the mitochondrial tricarboxylic acid (TCA) cycle (UniProt, P36957). It catalyzes the oxidative decarboxylation of alpha-ketoglutarate to succinyl-CoA, a critical step for energy production and metabolic flux (NCBI Gene ID: 4967). Beyond its role in ATP generation, OGDH serves as a key regulatory point for glutamate metabolism and cellular redox balance (PubMed, PMID: 25659514). In various cancers, OGDH is often upregulated or modified to support the high metabolic demands of rapidly proliferating cells, making it a target for metabolic inhibitors like devimistat (PubChem, CID: 46843343). Conversely, reduced activity of this enzyme is associated with neurodegenerative conditions such as Alzheimer's disease, where impaired mitochondrial function contributes to neuronal death (PubMed, PMID: 10448853). Therapeutic strategies targeting OGDH aim to either inhibit its activity to starve cancer cells or support its function to mitigate metabolic decline in aging and disease (StatPearls, NBK557531).

Other names

Alpha-ketoglutarate dehydrogenaseAKGDHE1 component of the 2-oxoglutarate dehydrogenase complexOxoglutarate decarboxylaseOGDC

Inhibition of the E1 and E2 components of the alpha-ketoglutarate dehydrogenase complex to disrupt the TCA cycle and induce metabolic stress in cancer cells.