The number of catalytic elements is crucial for the emergence of metabolic cores.
BACKGROUND
Different studies show evidence that several unicellular organisms display a cellular metabolic structure characterized by a set of enzymes which are always in an active state (metabolic core), while the rest of the molecular catalytic reactions exhibit on-off changing states. This self-organized enzymatic configuration seems to be an intrinsic characteristic of metabolism, common to all living cellular organisms. In a recent analysis performed with dissipative metabolic networks (DMNs) we have shown that this global functional structure emerges in metabolic networks with a relatively high number of catalytic elements, under particular conditions of enzymatic covalent regulatory activity.


RESULTS
Here, to investigate the mechanism behind the emergence of this supramolecular organization of enzymes, we have performed extensive DMNs simulations (around 15,210,000 networks) taking into account the proportion of the allosterically regulated enzymes and covalent enzymes present in the networks, the variation in the number of substrate fluxes and regulatory signals per catalytic element, as well as the random selection of the catalytic elements that receive substrate fluxes from the exterior. The numerical approximations obtained show that the percentages of DMNs with metabolic cores grow with the number of catalytic elements, converging to 100% for all cases.


CONCLUSIONS
The results show evidence that the fundamental factor for the spontaneous emergence of this global self-organized enzymatic structure is the number of catalytic elements in the metabolic networks. Our analysis corroborates and expands on our previous studies illustrating a crucial property of the global structure of the cellular metabolism. These results also offer important insights into the mechanisms which ensure the robustness and stability of living cells.
De la Fuente
Ildefonso M
IM
Department of Mathematics, Faculty of Science and Technology, University of the Basque Country, Vizcaya, Spain. mtpmadei@ehu.es
Vadillo
Fernando
F
Pérez-Pinilla
Martín-Blas
MB
Vera-López
Antonio
A
Veguillas
Juan
J
D000495:Allosteric Site; D001669:Biochemical Phenomena; D002384:Catalysis; D002477:Cells / Q000378:metabolism; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D004926:Escherichia coli / Q000378:metabolism*; D016480:Helicobacter pylori / Q000378:metabolism*; D007700:Kinetics; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D015233:Models, Statistical; D009991:Oscillometry; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D015398:Signal Transduction