Phase-plane geometries in coupled enzyme assays

Math Biosci. 2018 Dec:306:126-135. doi: 10.1016/j.mbs.2018.09.008. Epub 2018 Sep 24.

Abstract

The determination of a substrate or enzyme activity by coupling one enzymatic reaction with another easily detectable (indicator) reaction is a common practice in the biochemical sciences. Usually, the kinetics of enzyme reactions is simplified with singular perturbation analysis to derive rate or time course expressions valid under the quasi-steady-state and reactant stationary state assumptions. In this paper, the dynamical behavior of coupled enzyme catalyzed reaction mechanisms is studied by analysis of the phase-plane. We analyze two types of time-dependent slow manifolds - Sisyphus and Laelaps manifolds - that occur in the asymptotically autonomous vector fields that arise from enzyme coupled reactions. Projection onto slow manifolds yields various reduced models, and we present a geometric interpretation of the slow/fast dynamics that occur in the phase-planes of these reactions.

Keywords: Asymptotically autonomous vector field; Coupled enzyme assays; Differential-algebraic equation; Enzyme kinetics; Laelaps manifold; Michaelis–Menten reactions; Sisyphus manifold; Time-dependent slow manifold.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocatalysis
  • Biochemical Phenomena
  • Enzyme Activation
  • Enzyme Assays / statistics & numerical data*
  • Enzyme Precursors / metabolism
  • Enzymes / metabolism
  • Kinetics
  • Mathematical Concepts
  • Models, Biological
  • Models, Chemical
  • Reproducibility of Results

Substances

  • Enzyme Precursors
  • Enzymes