Reactome | DLD dimer dehydrogenates dihydrolipoyl

DLD dimer dehydrogenates dihydrolipoyl

Stable Identifier

R-HSA-9858589

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial matrix

Synonyms

N(6)-((R)-dihydrolipoyl)-L-lysyl-(protein) + NAD(+) => H(+) + N(6)-((R)-lipoyl)-L-lysyl-(protein) + NADH

ReviewStatus

5/5

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Dihydrolipoyl dehydrogenase (DLD), the E3 component of the 2-oxoadipate dehydrogenase metabolon, forms a homodimer that catalyzes the dehydrogenation of dihydrolipoyllysine residues by producing NADH from NAD+, with the help of the FAD cofactor (Brautigam et al., 2005). This reaction, in a side reaction not annotated here, is the main source of reactive oxygen species (ROS) in mitochondria (Ambrus et al., 2015). Deficiency of DLD activity due to mutations is a rare genetic disease (DLDD; MIM:246900; see Wongkittichote et al., 2023; reviewed in Ambrus & Adam-Viz, 2017).

Literature References

PubMed ID	Title	Journal	Year
26456061	Formation of reactive oxygen species by human and bacterial pyruvate and 2-oxoglutarate dehydrogenase multienzyme complexes reconstituted from recombinant components Ambrus, A, Nemeria, NS, Torocsik, B, Tretter, L, Nilsson, M, Jordan, F, Adam-Vizi, V	Free Radic Biol Med	2015
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 Nemeria, NS, Gerfen, G, Nareddy, PR, Yang, L, Zhang, X, Szostak, M, Jordan, F	Free Radic Biol Med	2018
15946682	Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations Brautigam, CA, Chuang, JL, Tomchick, DR, Machius, M, Chuang, DT	J Mol Biol	2005
28579060	Human dihydrolipoamide dehydrogenase (E3) deficiency: Novel insights into the structural basis and molecular pathomechanism Ambrus, A, Adam-Vizi, V	Neurochem Int	2018
37701333	Biochemical characterization of patients with dihydrolipoamide dehydrogenase deficiency Wongkittichote, P, Cuddapah, SR, Master, SR, Grange, DK, Dietzen, D, Roper, SM, Ganetzky, RD	JIMD Rep	2023