Supplementary material from "A facilitated diffusion model constrained by the probability isotherm: a pedagogical exercise in intuitive non-equilibrium thermodynamics"
Published on 2017-06-01T10:15:33Z (GMT) by
This paper seeks to develop a more thermodynamically sound pedagogy for students of biological transport than is currently available from either of the competing schools of linear non-equilibrium thermodynamics (LNET) or Michaelis–Menten kinetics (MMK). To this end, a minimal model of facilitated diffusion was constructed comprising four reversible steps: <i>cis-</i>substrate binding, <i>cis</i>→<i>trans</i> bound enzyme shuttling, <i>trans</i>-substrate dissociation and <i>trans</i>→<i>cis</i> free enzyme shuttling. All model parameters were subject to the second law constraint of the probability isotherm, which determined the unidirectional and net rates for each step and for the overall reaction through the law of mass action. Rapid equilibration scenarios require sensitive ‘tuning’ of the thermodynamic binding parameters to the equilibrium substrate concentration. All non-equilibrium scenarios show sigmoidal force–flux relations, with only a minority of cases having their <i>quasi</i>-linear portions close to equilibrium. Few cases fulfil the expectations of MMK relating reaction rates to enzyme saturation. This new approach illuminates and extends the concept of rate-limiting steps by focussing on the free energy dissipation associated with each reaction step and thereby deducing its respective relative chemical impedance. The crucial importance of an enzyme's being thermodynamically ‘tuned’ to its particular task, dependent on the <i>cis-</i> and <i>trans-</i>substrate concentrations with which it deals, is consistent with the occurrence of numerous isoforms for enzymes that transport a given substrate in physiologically different circumstances. This approach to kinetic modelling, being aligned with neither MMK nor LNET, is best described as intuitive non-equilibrium thermodynamics, and is recommended as a useful adjunct to the design and interpretation of experiments in biotransport.
Cite this collection
Chapman, Brian (2017): Supplementary material from "A facilitated diffusion model constrained by the probability isotherm: a pedagogical exercise in intuitive non-equilibrium thermodynamics". The Royal Society. Collection.