Theoretical approaches to the evolutionary optimization of glycolysis: thermodynamic and kinetic constraints.
It is analyzed whether the structural design of contemporary glycolysis can be explained theoretically on the basis of optimization principles originating from natural selection during evolution. Particular attention is paid to the problem of how the kinetic and thermodynamic properties of the glycolytic pathway are related to its stoichiometry with respect to the number and location of ATP-coupling sites. The mathematical analysis of a minimal model of unbranched energy-converting pathways shows that the requirement of high ATP-production rate favours a structural design that includes not only ATP-producing reactions (P-sites) but also ATP-consuming reactions (C-sites). It is demonstrated that, at fixed overall thermodynamic properties of a chain, the ATP-production rate may be enhanced by kinetic optimization. The ATP-production rate is increased if the C-sites are concentrated at the beginning and all the P-sites at the end of the pathway. An optimum is attained, which is characterized by numbers of coupling sites corresponding to those found in glycolysis. Various extensions of the minimal model are considered, which allow the effects of internal feedback-regulations, variable enzyme concentrations, and the symmetric branching of glycolysis at the aldolase step to be considered.
Heinrich
R
R
Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, Institut für Biologie, Germany.
Montero
F
F
Klipp
E
E
Waddell
T G
TG
Meléndez-Hevia
E
E
D000255:Adenosine Triphosphate / Q000378:metabolism*; D004734:Energy Metabolism; D004798:Enzymes / Q000378:metabolism; D005246:Feedback; D006019:Glycolysis; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D013816:Thermodynamics
D004798:Enzymes; D000255:Adenosine Triphosphate