Reactome | OADH complex synthesizes glutaryl-CoA from 2-OA

OADH complex synthesizes glutaryl-CoA from 2-OA

Stable Identifier

R-HSA-9858328

Type

Pathway

Species

Homo sapiens

Compartment

mitochondrial inner membrane, mitochondrial matrix

Synonyms

alpha-ketoadipate + CoASH + NAD+ => glutaryl-CoA + CO2 + NADH + H+, Oxidative decarboxylation of alpha-ketoadipate to glutaryl CoA by alpha-ketoglutarate dehydrogenase

ReviewStatus

5/5

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OADH complex synthesizes glutaryl-CoA from 2-OA

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The mitochondrial alpha-oxoadipate dehydrogenase complex (OADH, OADHC) catalyzes the overall reaction of 2-oxoadipate (OA), CoASH, and NAD+ to form glutaryl-CoA, CO2, and NADH. The complex contains multiple copies of three different enzymes, E1 (DHTKD1), E2 (DLST), and E3 (DLD), each with distinct catalytic activities. As in other dehydrogenase complexes, the lipoyl scaffold bound to DLST accepts the glutaryl moiety after the decarboxylation of OA by DHTKD1. Secondly, glutaryl is transferred to CoA by DLST, and finally, the dihydrolipoyl moiety is dehydrogenated by DLD using NAD+ (Nemeria et al., 2018; Zhang et al., 2020; Nemeria et al., 2021). Crystallographic studies show that in the OADH complex, DHTKD1 dimers bind to a 24-mer DLST core (Bezerra et al., 2020).

Literature References

PubMed ID	Title	Journal	Year
29191460	The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species Zhang, X, Jordan, F, Yang, L, Nareddy, PR, Nemeria, NS, Gerfen, G, Szostak, M	Free Radic Biol Med	2018
33946784	Toward an Understanding of the Structural and Mechanistic Aspects of Protein-Protein Interactions in 2-Oxoacid Dehydrogenase Complexes Zhang, X, Leandro, J, Jordan, F, Yang, L, Zhou, J, Houten, SM, Nemeria, NS	Life (Basel)	2021
32695416	Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism McCorvie, TJ, Kölker, S, Rutter, J, Foster, WR, Hicks, KG, Bailey, HJ, Okun, JG, Bezerra, GA, Sauer, SW, Yue, WW, Dimitrov, B	IUCrJ	2020
32303640	Structure-function analyses of the G729R 2-oxoadipate dehydrogenase genetic variant associated with a disorder of l-lysine metabolism Zhang, X, Jordan, F, Brukh, R, Ambrus, A, Leandro, J, Ozohanics, O, Nemeria, NS, Nagy, B, Gerfen, G, Lazarus, M, Houten, S	J Biol Chem	2020