EC Number   |
General Information |
Reference |
|---|
   1.3.8.12 | evolution |
(2S)-methylsuccinyl-CoA dehydrogenase (MCD) belongs to the family of FAD-dependent acyl-CoA dehydrogenase (ACD). Compared with other ACDs, MCD contains an about 170-residue-long N-terminal extension that structurally mimics a dimer-dimer interface of these enzymes that are canonically organized as tetramers. MCD apparently evolved toward preventing the nonspecific oxidation of succinyl-CoA, which is a close structural homologue of (2S)-methylsuccinyl-CoA and an essential intermediate in central carbon metabolism |
-, 763257 |
| 1.3.8.12 | evolution |
the members of the flavin adenosine dinucleotide (FAD)-dependent acyl-CoA dehydrogenase and acyl-CoA oxidase families catalyze similar reactions and share common structural features. But both enzyme families feature opposing reaction specificities in respect to dioxygen. Dehydrogenases react with electron transfer flavoproteins as terminal electron acceptors and do not show a considerable reactivity with dioxygen, whereas dioxygen serves as a bona fide substrate for oxidases |
763481 |
| 1.3.8.12 | malfunction |
convertion of (2S)-methylsuccinyl-CoA dehydrogenase (Mcd), a member of the ACAD enzyme family, into a (2S)-methylsuccinyl-CoA oxidase (Mco) through three active site mutations |
763481 |
| 1.3.8.12 | metabolism |
(2S)-methylsuccinyl-CoA dehydrogenase (MCD) is a key enzyme of the ethylmalonyl-CoA pathway for acetate assimilation |
-, 763257 |
| 1.3.8.12 | metabolism |
the enzyme is involved in the ethylmalonyl-CoA pathway, an acetyl-CoA assimilation strategy |
730403 |
| 1.3.8.12 | more |
active site structure, structure-function analysis, overview |
-, 763257 |
| 1.3.8.12 | physiological function |
acyl-CoA dehydrogenases (ACADs) are flavoproteins that catalyze the flavin adenosine dinucleotide (FAD)-dependent oxidation of alpha,beta-carbon bonds in acyl-CoA thioesters. ACADs are found in all kingdoms of life and are part of various metabolic pathways, such as amino acid oxidation, choline metabolism and most prominently, the initial step in fatty acid beta-oxidation. ACADs transfer the electrons from the substrate to an electron transfer flavoprotein (ETF), which in turn funnels the electrons into a membrane bound electron transport chain and from there to the final electron acceptor. The reaction of ACADs can be divided into a reductive and an oxidative half-reaction. The reductive half-reaction is initiated by abstraction of the pro-R-alpha-proton of the acyl-CoA thioester by a conserved active site glutamate. The concomitant hydride transfer of the pro-R-beta-hydrogen to the N5 atom of the isoalloxazine ring of the FAD cofactor proceeds via an enolate-like intermediate, which forms a charge-transfer complex (CTC) with the FAD. Although the substrate is rapidly converted into the CTC, no product is formed in the absence of ETF or another suitable electron acceptor The reaction is completed with the electron transfer from the CTC to ETF during the oxidative half-reaction. The oxidative half-reaction consists of two successive inter-protein one-electron transfers between reduced ACAD and two oxidized ETFs. This results in the re-oxidation of the ACAD bound FAD and yields two ETFs in the semiquinone state (ETFsq). In contrast to ACADs, acyl-CoA oxidases (ACXs) do not require an ETF partner and directly use dioxygen as a final electron acceptor |
763481 |
| 1.3.8.12 | physiological function |
MCD prevents the nonspecific oxidation of succinyl-CoA, which is a close structural homologue of (2S)-methylsuccinyl-CoA and an essential intermediate in central carbon metabolism. Structure-function analysis, overview |
-, 763257 |
