OGDH
OGDH (oxoglutarate dehydrogenase, also known as E1k, OGDC-E1, OGDH2 and KGD1) is the E1o component of the 2-oxoglutarate dehydrogenase complex. It catalyses the rate-limiting first step in the conversion of 2-oxoglutarate to succinyl-CoA in the Krebs cycle. Browse Assay Genie's current range of OGDH research reagents below, or read on for the biology behind the target.
OGDH is the 2-oxoglutarate dehydrogenase (E1o) component of the 2-oxoglutarate dehydrogenase complex (OGDHC). It performs the first step of the complex, which is rate limiting for the overall conversion of 2-oxoglutarate to succinyl-CoA and CO2. Using thiamine diphosphate (ThDP) as a cofactor, it catalyses the irreversible decarboxylation of 2-oxoglutarate (alpha-ketoglutarate). The decarboxylated acyl intermediate is then transferred to an oxidised dihydrolipoyl group that is covalently amidated to the E2 enzyme, dihydrolipoyllysine-residue succinyltransferase (DLST). This places the OGDH protein at a key point in the Krebs (citric acid) cycle, a common pathway for the oxidation of carbohydrates, fatty acids and amino acids.
The enzyme is mainly active in the mitochondrion, and the OGDH gene product is located in the mitochondrial matrix. A fraction of the complex also localises to the nucleus. There it is required for lysine succinylation of histones, associating with KAT2A on chromatin and providing succinyl-CoA to this histone succinyltransferase. In vitro, OGDH can also decarboxylate 2-oxoadipate, though at a much lower rate than 2-oxoglutarate, and can convert 2-keto-4-hydroxyglutarate (KHG) and CoA into malyl-CoA. It belongs to the alpha-ketoglutarate dehydrogenase family.
HGNC classes the gene within the oxoglutarate dehydrogenase family and among the oxoglutarate dehydrogenase complex subunits. Its previous name was oxoglutarate (alpha-ketoglutarate) dehydrogenase (lipoamide). Alternative splicing produces multiple transcript variants that encode distinct isoforms. A congenital deficiency in 2-oxoglutarate dehydrogenase activity is believed to lead to hypotonia, metabolic acidosis and hyperlactatemia. Mouse and rat each have an orthologous Ogdh gene.
OGDH catalyses the rate-limiting first step of 2-oxoglutarate conversion to succinyl-CoA and CO2, making it central to studies of citric acid cycle flux.
As a matrix-located subunit of the OGDHC, OGDH is studied in the context of mitochondrial fuel oxidation of carbohydrates, fatty acids and amino acids.
A nuclear fraction of the complex associates with KAT2A and supplies succinyl-CoA for histone lysine succinylation.
Congenital deficiency of 2-oxoglutarate dehydrogenase activity is believed to cause hypotonia, metabolic acidosis and hyperlactatemia.
OGDH is the E1o component of the 2-oxoglutarate dehydrogenase complex. It decarboxylates 2-oxoglutarate using thiamine diphosphate and passes the acyl intermediate to the E2 enzyme DLST. This is the rate-limiting step in converting 2-oxoglutarate to succinyl-CoA and CO2 in the Krebs cycle.
OGDH is also called E1k, OGDC-E1, OGDH2 and KGD1, and its UniProt name is 2-oxoglutarate dehydrogenase complex component E1. Its earlier HGNC name was oxoglutarate (alpha-ketoglutarate) dehydrogenase (lipoamide). Alternative splicing gives multiple transcript variants encoding distinct isoforms.
Mouse and rat both carry an orthologous Ogdh gene. A congenital deficiency in 2-oxoglutarate dehydrogenase activity is believed to lead to hypotonia, metabolic acidosis and hyperlactatemia. Check the datasheet of any product for its validated reactivity.
Other Krebs cycle enzymes and subunits of the 2-oxoglutarate dehydrogenase complex, such as DLST, are natural companions for OGDH research.
Gene and protein annotations from HGNC, NCBI Gene and UniProt Q02218; product specifications from Assay Genie datasheets.