title: Allosteric regulation of phosphofructokinase controls the emergence of glycolytic oscillations in isolated yeast cells.
abstract: Oscillations are widely distributed in nature and synchronization of oscillators has been described at the cellular level (e.g. heart cells) and at the population level (e.g. fireflies). Yeast glycolysis is the best known oscillatory system, although it has been studied almost exclusively at the population level (i.e. limited to observations of average behaviour in synchronized cultures). We studied individual yeast cells that were positioned with optical tweezers in a microfluidic chamber to determine the precise conditions for autonomous glycolytic oscillations. Hopf bifurcation points were determined experimentally in individual cells as a function of glucose and cyanide concentrations. The experiments were analyzed in a detailed mathematical model and could be interpreted in terms of an oscillatory manifold in a three-dimensional state-space; crossing the boundaries of the manifold coincides with the onset of oscillations and positioning along the longitudinal axis of the volume sets the period. The oscillatory manifold could be approximated by allosteric control values of phosphofructokinase for ATP and AMP.
  
  
  METHODS
  The mathematical models described here have been submitted to the JWS Online Cellular Systems Modelling Database and can be accessed at http://jjj.mib.ac.uk/webMathematica/UItester.jsp?modelName=gustavsson5. [Database section added 14 May 2014 after original online publication].
authors.affiliation: Department of Physics, University of Gothenburg, Sweden.
authors.forename: Anna-Karin
authors.initials: AK
authors.lastname: Gustavsson
authors.forename: David D
authors.initials: DD
authors.lastname: van Niekerk
authors.forename: Caroline B
authors.initials: CB
authors.lastname: Adiels
authors.forename: Bob
authors.initials: B
authors.lastname: Kooi
authors.forename: Mattias
authors.initials: M
authors.lastname: Goksör
authors.forename: Jacky L
authors.initials: JL
authors.lastname: Snoep
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000494:Allosteric Regulation; D006019:Glycolysis; D007700:Kinetics; D008954:Models, Biological; D025221:Phosphofructokinases / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000378:metabolism*
chemical_list: D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D025221:Phosphofructokinases
keywords: cell heterogeneity; glycolysis; limit cycle oscillation; mathematical model; microfluidic chamber