Control analysis of transition times in metabolic systems.
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ABSTRACT:
SUBMITTER: Melendez-Hevia E
PROVIDER: S-EPMC1136630 | biostudies-other | 1990 Jan
REPOSITORIES: biostudies-other
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Project description:In this paper we study the transitions between steady states in metabolic systems. In order to deal with this task we divided the total metabolite concentration at steady state, sigma, into two new fractions, delta (the Output Transition Time) and tau beta (Input Transition Time), which are related with the course of output and input mass to the system respectively. We show the equivalence time between these terms and the Total Transition Time, tau T, previously defined [Easterby (1986) Biochem. J. 233, 871-875]. Next, we define a new magnitude, the Output Passivity of a transition, rho, which quantifies a new aspect of the transition phase that we call the passivity of the output progress curve. With these magnitudes, all of them being experimentally accessible, several features of the transient state can be measured. We apply the present analysis to (a) the case of coupled enzyme assays, which allows us to reach conclusions about the progress curves in these particular transitions and the equivalence between tau sigma and tau delta, and (b) some experimental results that allow us to discuss the biological significance of the Output Passivity in the transition between steady states in metabolic systems.
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Project description:A theory is developed that integrates approaches to the analysis of pathway transient response and metabolic control analysis. A Temporal Control Coefficient is defined that is a measure of the system's transient response to modulation of enzyme activity or concentration. The approach allows for the analysis of the establishment of a steady state from rest, of the system's 'agility' of response to minor perturbations of a pre-existing steady state and of the macroscopic transition between steady states. In the last-mentioned case it is shown that, like the transient time itself, the control of transient response retains the property of independence from the mechanism of the transition. In consequence, the Temporal Control Coefficient can be defined in terms of the control properties of the initial and final states alone without reference to the mechanism of transition. A summation property is shown to apply to the Temporal Control Coefficients in each case. Connectivity relationships between elasticities and Temporal Control Coefficients are also established.
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Project description:Control analysis of transit time, defined as tau = delta/J, has previously been considered with the constraint of low enzyme concentrations compared with free pools of metabolites [Meléndez-Hevia, Torres, Sicilia and Kacser (1990) Biochem. J. 265, 195-202]. One of the conclusions was that the sum of the control coefficients of the transition time with respect to enzyme concentration was -1. Here we demonstrate that, if the enzyme-bound pools are taken into consideration (which would be important at high enzyme concentrations and high affinities), the sum lies between 0 and -1. The transition time between two steady states, which are frequent physiological events, is mainly governed by time constants involved in changing the enzyme concentrations. Some physiological and evolutionary aspects are discussed.
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