Reactome | OGDH dimer decarboxylates 2-OG

OGDH dimer decarboxylates 2-OG

Stable Identifier

R-HSA-71401

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial matrix

Synonyms

2-oxoglutarate + H(+) + N(6)-((R)-lipoyl)-L-lysyl-(dihydrolipoyllysine-residue succinyltransferase) => CO2 + N(6)-((R)-S(8)-succinyldihydrolipoyl)-L-lysyl-(dihydrolipoyllysine-residue succinyltransferase), Oxidative decarboxylation of alpha-ketoglutarate to succinyl CoA by alpha-ketoglutarate dehydrogenase

ReviewStatus

5/5

Locations in the PathwayBrowser

Expand all

General

SBML | | PDF

SVG | | PPTX | SBGN

Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

2-Oxoglutarate dehydrogenase complex (OGDHC) component E1 (OGDH) catalyzes the decarboxylation of alpha-oxoglutarate (αOG), at the same time transferring the resulting succinyl onto the lipoyl moiety of the E2 component (DLST) which gets reduced in the process. The enzyme is a homodimer, with each monomer binding one Ca2+ ion, one Mg2+ ion, and one thiamin molecule (PDB 7WGR; Zhong et al., 2022). OGDH activity is enhanced by ATP and NADH and decreased by Ca2+ and ADP. An alternative substrate of OGDH is 2-oxoadipate, which, in the end, leads to glutaryl-CoA, with a high amount of superoxide/ H2O2 produced as a side product (Armstrong et al., 2014; Nemeria et al., 2014; Nemeria et al., 2017).

Literature References

PubMed ID	Title	Journal	Year
25210035	Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate Jordan, F, Adam-Vizi, V, Patel, H, Zhou, J, Ambrus, A, Nemeria, NS, Gerfen, G, Tretter, L, Wang, J	J Biol Chem	2014
28435050	The human Krebs cycle 2-oxoglutarate dehydrogenase complex creates an additional source of superoxide/hydrogen peroxide from 2-oxoadipate as alternative substrate Jordan, F, Nareddy, PR, Nemeria, NS, Gerfen, G, Guevara, E, Szostak, M	Free Radic Biol Med	2017
24495017	Studies on the regulation of the human E1 subunit of the 2-oxoglutarate dehydrogenase complex, including the identification of a novel calcium-binding site Armstrong, CT, Denton, RM, Anderson, JL	Biochem J	2014
35272141	Structural basis for the activity and regulation of human α-ketoglutarate dehydrogenase revealed by Cryo-EM Xu, Y, Zhou, D, Yang, W, Zhong, Y, Ma, X, Yu, X, Gao, Y, Chen, H	Biochem Biophys Res Commun	2022