ArticleBMC biochemistry2011
Detailed kinetics and regulation of mammalian 2-oxoglutarate dehydrogenase.
Article in BMC biochemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 43 citations in OpenAlex.
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- Atorvastatin Mitigates Hypercholesterolemia-Induced Alterations in Cerebral Mitochondrial Dehydrogenases in Rats.International journal of molecular sciences · 2026Article
- Niclosamide nanoparticles enhance pancreatic cancer sensitivity to gemcitabine via HIF-1α inhibition.iScience · 2025Article
- Mitochondrial Regulation of Ferroptosis in Cancer Therapy.International journal of molecular sciences · 2023Review
- MRPS36 provides a structural link in the eukaryotic 2-oxoglutarate dehydrogenase complex.Open biology · 2023Article
- Untargeted Metabolomics Studies of H9c2 Cardiac Cells Submitted to Oxidative Stress, β-Adrenergic Stimulation and Doxorubicin Treatment: Investigation of Cardiac Biomarkers.Frontiers in molecular biosciences · 2022Article
- Detailed evaluation of pyruvate dehydrogenase complex inhibition in simulated exercise conditions.Biophysical journal · 2021Article
- An acidic residue buried in the dimer interface of isocitrate dehydrogenase 1 (IDH1) helps regulate catalysis and pH sensitivity.The Biochemical journal · 2020Article
- Unstructured regions of large enzymatic complexes control the availability of metabolites with signaling functions.Cell communication and signaling : CCS · 2020Review
- Complex Mitochondrial Dysfunction Induced by TPPCells · 2020Article
- An Updated View on the Molecular Pathomechanisms of Human Dihydrolipoamide Dehydrogenase Deficiency in Light of Novel Crystallographic Evidence.Neurochemical research · 2019Review
- The Involvement of MgOxidative medicine and cellular longevity · 2017Review
- Mitochondrial Probe Methyltriphenylphosphonium (TPMP) Inhibits the Krebs Cycle Enzyme 2-Oxoglutarate Dehydrogenase.PloS one · 2016Article
- Structural alterations by five disease-causing mutations in the low-pH conformation of human dihydrolipoamide dehydrogenase (hLADH) analyzed by molecular dynamics - Implications in functional loss and modulation of reactive oxygen species generation by pathogenic hLADH forms.Biochemistry and biophysics reports · 2015Article
- Determination of the catalytic mechanism for mitochondrial malate dehydrogenase.Biophysical journal · 2015Article
- Teaching the fundamentals of electron transfer reactions in mitochondria and the production and detection of reactive oxygen species.Redox biology · 2015Review
- The 2-oxoacid dehydrogenase complexes in mitochondria can produce superoxide/hydrogen peroxide at much higher rates than complex I.The Journal of biological chemistry · 2014Article
- Enhanced charge-independent mitochondrial free Ca(2+) and attenuated ADP-induced NADH oxidation by isoflurane: Implications for cardioprotection.Biochimica et biophysica acta · 2012Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMitochondrial 2-oxoglutarate (α-ketoglutarate) dehydrogenase complex (OGDHC), a key regulatory point of tricarboxylic acid (TCA) cycle, plays vital roles in multiple pathways of energy metabolism and biosynthesis. The catalytic mechanism and allosteric regulation of this large enzyme complex are not fully understood. Here computer simulation is used to test possible catalytic mechanisms and mechanisms of allosteric regulation of the enzyme by nucleotides (ATP, ADP), pH, and metal ion cofactors (Ca(2+) and Mg(2+)).
resultsA model was developed based on an ordered ter-ter enzyme kinetic mechanism combined with con-formational changes that involve rotation of one lipoic acid between three catalytic sites inside the enzyme complex. The model was parameterized using a large number of kinetic data sets on the activity of OGDHC, and validated by comparison of model predictions to independent data.
conclusionsThe developed model suggests a hybrid rapid-equilibrium ping-pong random mechanism for the kinetics of OGDHC, consistent with previously reported mechanisms, and accurately describes the experimentally observed regulatory effects of cofactors on the OGDHC activity. This analysis provides a single consistent theoretical explanation for a number of apparently contradictory results on the roles of phosphorylation potential, NAD (H) oxidation-reduction state ratio, as well as the regulatory effects of metal ions on ODGHC function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.