1. On the dynamics of the adenylate energy system: homeorhesis vs homeostasis
- Author
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Jesus M. Cortes, Mathieu Desroches, Luis Martínez, Serafim Rodrigues, Edelmira Valero, Iker Malaina, Ildefonso M. De la Fuente, University of the Basque Country [Bizkaia] ( UPV/EHU ), BioCruces Research Institute, University of the Basque Country [Bizkaia] ( UPV/EHU ) -Cruces University Hospital, IKERBASQUE, IKERBASQUE, Basque Foundation for Science, 48011, Bilbao, Spain, University of Castilla-La Mancha ( UCLM ), Multiscale dYnamiCs in neuroENdocrine AxEs ( Mycenae ), Inria Paris-Rocquencourt, Institut National de Recherche en Informatique et en Automatique ( Inria ) -Institut National de Recherche en Informatique et en Automatique ( Inria ), Plymouth University, U.K., University of the Basque Country [Bizkaia] (UPV/EHU), University of the Basque Country [Bizkaia] (UPV/EHU)-Hospital Universitario Cruces = Cruces University Hospital, University of Castilla-La Mancha (UCLM), Multiscale dYnamiCs in neuroENdocrine AxEs (Mycenae), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Plymouth University, University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU)-Hospital Universitario Cruces = Cruces University Hospital, Ikerbasque - Basque Foundation for Science, and Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM)
- Subjects
Periodicity ,Bioenergetics ,BIOCHEMISTRY AND MOLECULAR BIOLOGY ,Biochemistry ,Systems Science ,chemistry.chemical_compound ,0302 clinical medicine ,Adenosine Triphosphate ,Adenine nucleotide ,physarum polycephalum ,Homeostasis ,Energy charge ,ComputingMilieux_MISCELLANEOUS ,0303 health sciences ,Multidisciplinary ,pancreatic beta-cell ,yeast sacchcromyces-cerevisiae ,Adenosine Diphosphate ,AGRICULTURAL AND BIOLOGICAL SCIENCES ,[ SCCO.NEUR ] Cognitive science/Neuroscience ,Physical Sciences ,Research Article ,Adenosine monophosphate ,Computer and Information Sciences ,Science ,[MATH.MATH-DS]Mathematics [math]/Dynamical Systems [math.DS] ,[ MATH.MATH-DS ] Mathematics [math]/Dynamical Systems [math.DS] ,Adenylate kinase ,Biology ,cellular metabolic structure ,Models, Biological ,03 medical and health sciences ,Animals ,Humans ,Computer Simulation ,030304 developmental biology ,long-range correlations ,Homeorhesis ,MEDICINE ,[SCCO.NEUR]Cognitive science/Neuroscience ,intracellular ATP concentration ,Biology and Life Sciences ,tobacco BY-2 cells ,Adenosine Monophosphate ,Adenosine diphosphate ,Kinetics ,Metabolism ,chemistry ,Nonlinear Dynamics ,Biophysics ,escherichia-coli ,biochemical oscillations ,Energy Metabolism ,Adenosine triphosphate ,adenine-nucleotide concentrations ,030217 neurology & neurosurgery ,Mathematics - Abstract
Biochemical energy is the fundamental element that maintains both the adequate turnover of the biomolecular structures and the functional metabolic viability of unicellular organisms. The levels of ATP, ADP and AMP reflect roughly the energetic status of the cell, and a precise ratio relating them was proposed by Atkinson as the adenylate energy charge (AEC). Under growth-phase conditions, cells maintain the AEC within narrow physiological values, despite extremely large fluctuations in the adenine nucleotides concentration. Intensive experimental studies have shown that these AEC values are preserved in a wide variety of organisms, both eukaryotes and prokaryotes. Here, to understand some of the functional elements involved in the cellular energy status, we present a computational model conformed by some key essential parts of the adenylate energy system. Specifically, we have considered (I) the main synthesis process of ATP from ADP, (II) the main catalyzed phosphotransfer reaction for interconversion of ATP, ADP and AMP, (III) the enzymatic hydrolysis of ATP yielding ADP, and (IV) the enzymatic hydrolysis of ATP providing AMP. This leads to a dynamic metabolic model (with the form of a delayed differential system) in which the enzymatic rate equations and all the physiological kinetic parameters have been explicitly considered and experimentally tested in vitro. Our central hypothesis is that cells are characterized by changing energy dynamics (homeorhesis). The results show that the AEC presents stable transitions between steady states and periodic oscillations and, in agreement with experimental data these oscillations range within the narrow AEC window. Furthermore, the model shows sustained oscillations in the Gibbs free energy and in the total nucleotide pool. The present study provides a step forward towards the understanding of the fundamental principles and quantitative laws governing the adenylate energy system, which is a fundamental element for unveiling the dynamics of cellular life.
- Published
- 2014
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