Prediction of Muscle Energy States at Low Metabolic Rates Requires Feedback Control of Mitochondrial Respiratory Chain Activity by Inorganic Phosphate

Joep P. J. Schmitz*, Jeroen A. L. Jeneson, Joep W. M. van Oorschot, Jeanine J. Prompers, Klaas Nicolay, Peter A. J. Hilbers, Natal A. W. van Riel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The regulation of the 100-fold dynamic range of mitochondrial ATP synthesis flux in skeletal muscle was investigated. Hypotheses of key control mechanisms were included in a biophysical model of oxidative phosphorylation and tested against metabolite dynamics recorded by 31 P nuclear magnetic resonance spectroscopy (P-31 MRS). Simulations of the initial model featuring only ADP and Pi feedback control of flux failed in reproducing the experimentally sampled relation between myoplasmic free energy of ATP hydrolysis (Delta G(p) = Delta Gp o'+RT In ([ADP][Pi]/[ATP]) and the rate of mitochondrial ATP synthesis at low fluxes (

Original languageEnglish
Article number34118
Number of pages14
JournalPLoS ONE [E]
Volume7
Issue number3
DOIs
Publication statusPublished - 28 Mar 2012

Keywords

  • HUMAN SKELETAL-MUSCLE
  • OXIDATIVE-PHOSPHORYLATION
  • IN-VIVO
  • ATP HYDROLYSIS
  • SYSTEMS BIOLOGY
  • P-31 MRS
  • RECOVERY
  • ACTIVATION
  • ENERGETICS
  • EXERCISE

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