Disease relevance of succ-S-CoA

• The amino acid sequence of the mature alpha subunit shows an extraordinary degree of homology to the alpha subunit of Escherichia coli succinyl-CoA synthetase, with greater than 70% of the residues identical [1].
• Characterization of nucleoside-diphosphate kinase from Pseudomonas aeruginosa: complex formation with succinyl-CoA synthetase [2].
• The coupling of a decrease in BDH activity with an increase in activity of succinyl-CoA: acetoacetyl-CoA transferase in hepatoma cells may play a role in generating additional energy required for the rapid growth of tumor cells [3].
• Homogeneous beta-ketoadipate succinyl-CoA transferase (EC 2.8.3.6) preparations were obtained from extracts of Acinetobacter calcoaceticus and Pseudomonas putida [4].
• Delta-Aminolevulinic acid synthase (succinyl-CoA: glycine C-succinyltransferase (decarboxylating) EC 2.3.1.37) was purified from Rhodopseudomonas spheroides [5].

High impact information on succ-S-CoA

• Markedly decreased succinyl-CoA synthetase activity due to a deleterious mutation in SUCLA2, the gene encoding the beta subunit of the ADP-forming succinyl-CoA synthetase ligase, was found in muscle mitochondria of patients with encephalomyopathy and mtDNA depletion [6].
• A controversy has existed in the literature for the past several years regarding the number of vertebrate genes encoding the mitochondrial protein that initiates the first step in heme biosynthesis, delta-aminolevulinate synthase [ALAS; succinyl-CoA: glycine C-succinyltransferase (decarboxylating), EC 2.3.1.37] [7].
• Succinyl-CoA synthetase [succinate-CoA ligase (GDP-forming); EC 6.2.1.4] of rat liver, an alpha beta dimer, is a component of the enzymology of the tricarboxylic acid cycle and functions within the mitochondrial matrix [1].
• L-Methylmalonyl-CoA mutase (MUT) is an adenosylcobalamin (AdoCbl)-requiring mitochondrial matrix enzyme that catalyzes the isomerization of L-methylmalonyl-CoA to succinyl-CoA [8].
• Whereas ACOT4 mainly hydrolyzes succinyl-CoA, ACOT8 preferentially hydrolyzes longer dicarboxylyl-CoA esters (glutaryl-CoA, adipyl-CoA, suberyl-CoA, sebacyl-CoA, and dodecanedioyl-CoA) [9].

Chemical compound and disease context of succ-S-CoA

• In Methylobacterium extorquens AM1, a mutant defective in the MMAA homolog meaB was unable to grow on C(1) and C(2) compounds because of the inability to convert methylmalonyl-CoA to succinyl-CoA (Korotkova N., Chistoserdova, L., Kuksa, V., and Lidstrom, M. E. (2002) J. Bacteriol. 184, 1750-1758) [10].
• Affinity labeling of succinyl-CoA synthetase from porcine heart and Escherichia coli with oxidized coenzyme A disulfide [11].
• Adenosine 5'-O-(3-thio)triphosphate, a substrate and potent inhibitor of Escherichia coli succinyl-CoA synthetase. Additional evidence for a cooperative alternating-sites mechanism [12].
• Site-directed mutagenesis of Escherichia coli succinyl-CoA synthetase. Histidine 142 alpha is a facilitative catalytic residue [13].
• Well formed, tetragonal prisms of succinyl-CoA synthetase from Escherichia coli have been crystallized at room temperature from ammonium sulfate and mixtures of sodium and potassium phosphates [14].

Biological context of succ-S-CoA

• The 33-kDa alpha subunit of succinyl-CoA synthetase of P. aeruginosa appears to undergo autophosphorylation in the presence of either ATP or GTP, although the presence of small amounts of Ndk activity may influence the level of such phosphorylation [2].
• Ndk enzyme activity is also associated with succinyl-CoA synthetase activity in P. aeruginosa, whose alpha and beta subunits show extensive sequence homology with those of E. coli and Dictyostelium discoideum [2].
• ATP may also exert negative effects by inhibiting other site binding of ATP or by interfering with same site succinyl-CoA binding at subsaturating concentrations of the latter [15].
• ATP exerts its stimulatory action on succinate---- succinyl-CoA exchange through an "other site" effect, i.e. in binding to the noncatalytic site of succinyl-CoA synthetase, it facilitates binding and release of succinyl-CoA at the catalytic site [15].
• Oxidative phosphorylation and substrate level phosphorylation catalyzed by succinyl-CoA synthetase found in the citric acid and the acetate:succinate CoA transferase/succinyl-CoA synthetase cycle contribute to mitochondrial ATP synthesis in procyclic Trypanosoma brucei [16].

Anatomical context of succ-S-CoA

• Nutrient secretagogues can increase the production of succinyl-CoA in rat pancreatic islets [17].
• Succinyl-CoA transferase does not bind to any of these membranes [18].
• CONCLUSION/INTERPRETATION: We provide evidence for the localization of two distinct activities of succinyl-CoA synthetase in the beta cell mitochondria [19].
• Succinyl-CoA synthetases from Escherichia coli and porcine heart muscle have been viewed as prototypes of two classes of the enzyme [20].
• These findings indicate that, in the Caco-2 cells, metabolic intermediates of the Krebs cycle undergo enzyme-to-enzyme channelling in the sequence of reactions catalysed by succinyl-CoA synthetase, succinate dehydrogenase and fumarase [21].

Associations of succ-S-CoA with other chemical compounds

• This would enable this aminotransferase to supply alpha-ketoglutarate to the alpha-ketoglutarate dehydrogenase complex and would, in part, account for secretagogues increasing the islet level of succinyl-CoA after they decrease the level of HMG-CoA [17].
• The data presented herein also suggest that the binding sites for other substrates (succinate, succinyl-CoA) are located either on the beta subunit or comprise part of both subunit types [22].
• Rapid scanning stopped-flow experiments of murine erythroid 5-aminolevulinate synthase demonstrate that reaction with glycine plus succinyl-CoA results in a pre-steady-state burst of quinonoid intermediate formation [23].
• Other secretagogues can increase production of succinyl-CoA secondary to increasing alpha-ketoglutarate production by glutamate dehydrogenase or mitochondrial aspartate aminotransferase followed by the alpha-ketoglutarate dehydrogenase reaction [17].
• Adenine and guanine nucleotide-specific succinyl-CoA synthetases in the clonal beta-cell mitochondria: implications in the beta-cell high-energy phosphate metabolism in relation to physiological insulin secretion [19].

Gene context of succ-S-CoA

• The newly defined genes express polypeptides of 41 kDa (sucC) and 31 kDa (sucD), corresponding to the beta and alpha subunits of succinyl-CoA synthetase, respectively [24].
• The genes encoding both subunits of the succinyl-CoA synthetase of Escherichia coli have been identified as distal genes of the suc operon, which also encodes the dehydrogenase (Elo; sucA) and succinyltransferase (E2o; sucB) components of the 2-oxoglutarate dehydrogenase complex [24].
• The primary structure of the succinyl-CoA synthetase of Escherichia coli has been deduced from the nucleotide sequence of a 2451-base-pair segment of DNA containing the corresponding sucC (beta subunit) and sucD (alpha subunit) genes [25].
• Two of these genes have recently been further characterized: YGR241c (YAP1802) encodes a yeast adaptor protein and YGR244c (LSC2) encodes the beta-subunit of the succinyl-CoA ligase [26].
• Expression of hypoxic/anaerobic genes was elevated in alpha-ketoglutarate dehydrogenase mutants, whereas expression of oxidative genes was diminished, consistent with a heme signaling defect caused by inadequate levels of the heme precursor, succinyl-CoA [27].

Analytical, diagnostic and therapeutic context of succ-S-CoA

• Affinity chromatography and affinity labeling of rat liver succinyl-CoA synthetase [28].
• Crystallization of succinyl-CoA synthetase from Escherichia coli [14].
• Pure preparations of the alpha and beta subunits of succinyl-CoA synthetase of Escherichia coli have been obtained by preparative gel electrophoresis in the presence of detergent or by gel filtration in acid urea solution [29].
• The transition between the native and denatured states of the tetrameric succinyl-CoA synthetase from Escherichia coli has been investigated by circular dichroism, fluorescence spectroscopy, cross-linking by glutaraldehyde and activity measurements [30].
• To confirm the identity of these two enzymes, individual subunits of ATP-specific and GTP-specific to succinyl-CoA synthetase were identified by Western blot analysis [19].

References