Contents

📒 Bazil 2013

Catalytic coupling of oxidative phosphorylation, ATP demand, and reactive oxygen species generation1

Sciwheel

Introduction

  • The biochemical equation of Complex III for the net reaction is shown as https://els-jbs-prod-cdn.literatumonline.com/cms/attachment/2037591218/2051990519/si1.gif

  • Previous models are either too simple or too complex

  • The model developed here maintains the features presented above in a tenable, well-constrained representation of the bc1 complex

Methods

Model structure

https://els-jbs-prod-cdn.literatumonline.com/cms/attachment/05903c8e-2c41-4eef-bf73-60cece4ca1e8/gr1_lrg.jpg

  • This model includes the redox biochemistry that occurs at the Qo-site and Qi-site of the complex and couples cyt c reduction with the first electron transfer from ubiquinol
  • This first electron transfer at the Qo-site is the one of the primary, rate-limiting steps in the catalytic cycle
  • we assume that up to two mobile electrons can exist at both the Qo-site and Qi-site
  • 6 states
  • The fractional substate occupancies and the state transitions are governed by the thermodynamic driving force of the redox biochemistry defined by the midpoint potentials some of them being pH-dependent
  • Binding polynomials for Qo, Qi site, and ISP FeS
  • Under the right circumstances when cyt bL is reduced, there is a small but significant level of SQ at the Qo-site
  • State transitions are governed by two primary Gibb’s free energies of reaction.
  • The net turnover flux through the enzyme: https://els-jbs-prod-cdn.literatumonline.com/cms/attachment/2037591218/2051990558/si45.gif
  • Superoxide production rate: https://els-jbs-prod-cdn.literatumonline.com/cms/attachment/2037591218/2051990559/si46.gif
  • analytic expressions for the states at steady state https://els-jbs-prod-cdn.literatumonline.com/cms/attachment/2037591218/2051990561/si48.gif
  • The analytical solution for each state contains ∼1000 terms, so they are not explicitly presented here (using KA method ?)

Results and Discussion

  • Table1: fixed parameter values obtained from the literature and used to simulate the model
    • midpoint potentials, stability constants, pKa values, and other parameters
  • Table2: fitted parameter values and sesitivity

https://els-jbs-prod-cdn.literatumonline.com/cms/attachment/3e7956df-d02b-46b6-97fc-433f33e6cf30/gr2_lrg.jpg https://els-jbs-prod-cdn.literatumonline.com/cms/attachment/a0f18956-6f7a-4997-ae14-3c724248b394/gr3_lrg.jpg https://els-jbs-prod-cdn.literatumonline.com/cms/attachment/50d7e1d8-6af2-4502-a756-47e44092e45d/gr4_lrg.jpg https://els-jbs-prod-cdn.literatumonline.com/cms/attachment/50d7e1d8-6af2-4502-a756-47e44092e45d/gr5_lrg.jpg https://els-jbs-prod-cdn.literatumonline.com/cms/attachment/da9f1a07-96c8-4979-aa05-0e64a0569af1/gr6_lrg.jpg

  • The cyt c binding constants were assumed to be similar to the fitted constants for horse heart cyt c, based on its apparent universal nature as a substrate for bc1 complexes from other species

https://els-jbs-prod-cdn.literatumonline.com/cms/attachment/40ed28ef-6571-48b8-a313-99a2ecac4de7/gr7_lrg.jpg

Reference


  1. Bazil JN, Vinnakota KC, Wu F, Beard DA. Analysis of the kinetics and bistability of ubiquinol:cytochrome c oxidoreductase. Biophys J. 2013;105(2):343-55. PMC3714890 ↩︎