Contents

πŸ“’ Mathemetical modeling of the citric acid cycle (CAC): a summary

Mathemetical modeling of the citric acid cycle (CAC)

Abbreviations

  • CAC: Citric acid cycle = tricarboxylic acid (TCA) cycle = Krebs cycle
  • Pyr: pyruvate
  • PDH : pyruvate dehydrogenase
  • CS: citrate synthase
  • ACO: aconitase
  • IDH: isocitrate dehydrogenase
    • IDH1: NADPH-dependent, soluable
    • IDH2: NADPH-dependent, mitochondrial
    • IDH3: NADH-dependent, mitochondrial
  • KGDH: alpha ketoglutarate dehydrogenase
  • SL: succinate-CoA ligase = Succinyl CoA synthetase (SCS) = succinate thiokinase (STK)
    • ATP-dependent
    • GTP-dependent
  • SDH: Succinate dehydrogenase = succinate-coenzyme Q reductase (SQR) = respiratory Complex II
  • FH: Fumarate hydratase
  • MDH: Malate dehydrogenase. Not the same as malic enzyme, which is COβ‚‚-forming
  • AAT: Aspartate aminotransferase = AST = glutamic-oaa transaminase (GOT)

ECME model

  • Cardiac mitochodria1, full cycle CAC
  • CAC reaction rates enhanced by calcium and ADP
  • Coupled with cardiac electrophysiology models later on

Nguyen model

  • Cardiac mitochodria2, full cycle CAC
  • Focused on effects of calcium and proton dynamics on CAC fluxes

Mogilevskaya and Demin model

  • Salicylate inhibition of TCA cycle in hepatocytes3
  • Latter half cycle of the CAC, with AST shunt and kg-malate carrier
  • SDH with random order bi-bi reaction and depencdece to ubiquinone
  • Model description

Berndt model

  • Neuron cell model4
  • Full cycle of CAC (Pyruvate as the sole substrate)
  • Study the inhibition on KGDH (e.g. in Alzheimer’s disease or other neurodegerative diseases)
  • Along with electron transport chain model, but no mitochodnrial calcium dynamics
  • Model description

Wu and Beard model

  • Liver and heart mitochondria5. Schema
  • Along with Oxidative Phosphorylation (OxPhos), Metabolite Transport, and Electrophysiology
  • 70~ish state variables and excessive binding polynomials
  • Model description

Reference


  1. Cortassa, S., Aon, M. A., MarbΓ‘n, E., Winslow, R. L., & O’Rourke, B. (2003). An integrated model of cardiac mitochondrial energy metabolism and calcium dynamics. Biophysical journal, 84(4), 2734–2755. doi:10.1016/S0006-3495(03)75079-6 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1201507/ ↩︎

  2. Nguyen, M.-H. T., Dudycha, S. J., & Jafri, M. S. (2007). Effect of Ca2+ on cardiac mitochondrial energy production is modulated by Na+ and H+ dynamics. American Journal of Physiology. Cell Physiology, 292(6), C2004-20. https://www.physiology.org/doi/full/10.1152/ajpcell.00271.2006 ↩︎

  3. Mogilevskaya, E., Demin, O., & Goryanin, I. (2006). Kinetic model of mitochondrial Krebs cycle: unraveling the mechanism of salicylate hepatotoxic effects. Journal of Biological Physics, 32(3–4), 245–271. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2651525 ↩︎

  4. Berndt, N., Bulik, S., & HolzhΓΌtter, H.-G. (2012). Kinetic Modeling of the Mitochondrial Energy Metabolism of Neuronal Cells: The Impact of Reduced Ξ±-Ketoglutarate Dehydrogenase Activities on ATP Production and Generation of Reactive Oxygen Species. International journal of cell biology, 2012, 757594. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376505 ↩︎

  5. Wu, F., Yang, F., Vinnakota, K. C., & Beard, D. A. (2007). Computer modeling of mitochondrial tricarboxylic acid cycle, oxidative phosphorylation, metabolite transport, and electrophysiology. The Journal of Biological Chemistry, 282(34), 24525–24537. ↩︎