Quantitative full time course analysis of nonlinear enzyme cycling kinetics

Sci Rep. 2013:3:2658. doi: 10.1038/srep02658.


Enzyme inhibition due to the reversible binding of reaction products is common and underlies the origins of negative feedback inhibition in many metabolic and signaling pathways. Product inhibition generates non-linearity in steady-state time courses of enzyme activity, which limits the utility of well-established enzymology approaches developed under the assumption of irreversible product release. For more than a century, numerous attempts to find a mathematical solution for analysis of kinetic time courses with product inhibition have been put forth. However, no practical general method capable of extracting common enzymatic parameters from such non-linear time courses has been successfully developed. Here we present a simple and practical method of analysis capable of efficiently extracting steady-state enzyme kinetic parameters and product binding constants from non-linear kinetic time courses with product inhibition and/or substrate depletion. The method is general and applicable to all enzyme systems, independent of reaction schemes and pathways.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Computer Simulation
  • Enzymes / metabolism*
  • Kinetics
  • Models, Biological
  • Substrate Specificity


  • Enzymes