Reactome | DLD dimer dehydrogenates dihydrolipoyl

DLD dimer dehydrogenates dihydrolipoyl

Stable Identifier

R-HSA-9859172

Type

Reaction [transition]

Species

Homo sapiens

Compartment

mitochondrial matrix

ReviewStatus

5/5

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Dihydrolipoyl dehydrogenase (DLD), the E3 component of the branched-chain alpha-keto acid dehydrogenase complex (BCKDH), 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 characterized by neonatal lactic acidosis due to lack of pyruvate dehydrogenase activity, although symptoms of BCKDH deficiency may also be present (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 Jordan, F, Adam-Vizi, V, Nilsson, M, Ambrus, A, Torocsik, B, Nemeria, NS, Tretter, L	Free Radic Biol Med	2015
15946682	Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations Tomchick, DR, Machius, M, Chuang, DT, Chuang, JL, Brautigam, CA	J Mol Biol	2005
28579060	Human dihydrolipoamide dehydrogenase (E3) deficiency: Novel insights into the structural basis and molecular pathomechanism Adam-Vizi, V, Ambrus, A	Neurochem Int	2018
37701333	Biochemical characterization of patients with dihydrolipoamide dehydrogenase deficiency Ganetzky, RD, Dietzen, D, Wongkittichote, P, Cuddapah, SR, Grange, DK, Master, SR, Roper, SM	JIMD Rep	2023