OGDH
Description
The OGDH (oxoglutarate dehydrogenase) is a protein-coding gene located on chromosome 7.
The OGDH gene, located on chromosome 7, encodes a subunit of the 2-oxoglutarate dehydrogenase complex. This complex is essential for the citric acid cycle, catalyzing the conversion of 2-oxoglutarate to succinyl-CoA and CO2. The enzyme utilizes thiamine pyrophosphate as a cofactor and is found in the mitochondrial matrix. The OGDH subunit facilitates the decarboxylation of 2-oxoglutarate by acting as a base to remove a proton, with key residues involved in the catalysis including His 260, Phe 227, Gln685, His 729, Ser302, and His 298. The complex functions by keeping necessary substrates close together, ensuring a favorable orientation for the reaction. Additionally, the complex minimizes unwanted side reactions by channeling intermediates between subunits.
The 2-oxoglutarate dehydrogenase complex (OGDHC) is a multi-enzyme complex that catalyzes the irreversible decarboxylation of 2-oxoglutarate to succinyl-CoA and CO2. This reaction is the first step of the citric acid cycle and is rate-limiting for the overall conversion of 2-oxoglutarate to succinyl-CoA. The 2-oxoglutarate dehydrogenase (E1o) component of the OGDHC catalyzes the decarboxylation of 2-oxoglutarate using the thiamine diphosphate (ThDP) cofactor and then transfers the decarboxylated acyl intermediate to the dihydrolipoyl group of the E2 component (dihydrolipoyllysine-residue succinyltransferase or DLST). The OGDHC plays a key role in the Krebs (citric acid) cycle, a pathway for oxidizing fuel molecules such as carbohydrates, fatty acids, and amino acids. In addition to its mitochondrial role, the OGDHC has been shown to localize to the nucleus, where it is required for lysine succinylation of histones. The OGDHC interacts with KAT2A on chromatin, providing succinyl-CoA to the histone succinyltransferase KAT2A.
OGDH is also known as AKGDH, E1k, E1o, KGD1, OGDC, OGDH-E1, OGDH2, OGDHD.
