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.
Highlights
Living cells are essentially highly evolved dynamic reactive structures, in which the most complex known molecules are synthesized and destroyed by means of a sophisticated metabolic network characterized by hundreds to thousands of biochemical reactions, densely integrated, shaping one of the most complex dynamic systems in nature [1,2].Energy is the fundamental element for the viability of the cellular metabolic network
To understand the dynamics of the main enzymatic reactions interconverting the adenine nucleotides we have analyzed a biochemical model for the adenylate energy system using the system of delay differential equations (12) to account for the asynchronous conditions inside the cell
Scenario I Scenario I represents the fundamental analysis of the paper, being l the main control parameter, which models the energy level stored in the proton gradient generated by the enzymatic oxidation of input nutrients, and represents the modifying factor for the adenosine 59-triphosphate (ATP) synthesis in the system due to substrate intake
Summary
Living cells are essentially highly evolved dynamic reactive structures, in which the most complex known molecules are synthesized and destroyed by means of a sophisticated metabolic network characterized by hundreds to thousands of biochemical reactions, densely integrated, shaping one of the most complex dynamic systems in nature [1,2].Energy is the fundamental element for the viability of the cellular metabolic network. Different nucleosides can bind to three phosphates which may serve to store biochemical energy i.e., GTP, (d)CTP, (d)TTP and (d)UTP [5], there exists a consensus that adenosine 59-. Triphosphate (ATP) is the principal molecule for storing and transferring energy in cells. From the simplest bacteria to human cells, use ATP (Mg-ATP) as their major energy source for metabolic reactions [6,7,8], and the levels of ATP, ADP and AMP reflect roughly the energetic status of the cell [7]. ATP is originated from different classes of metabolic reactions, mainly substrate-level phosphorylation, cellular respiration, photophosphorylation and fermentation, and it is used by enzymes and structural proteins in all main cytological processes, i.e., motility, cell division, biosynthetic reactions, cell cycle, allosteric regulations, and fast synaptic modulation [7,8,9]
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