Sequential Activation of Metabolic Pathways: a Dynamic Optimization Approach

Diego A. Oyarzún, Brian P. Ingalls, Richard H. Middleton, Dimitrios Kalamatianos

Research output: Contribution to journalArticlepeer-review

Abstract

The regulation of cellular metabolism facilitates robust cellular operation in the face of changing external conditions. The cellular response to this varying environment may include the activation or inactivation of appropriate metabolic pathways. Experimental and numerical observations of sequential timing in pathway activation have been reported in the literature. It has been argued that such patterns can be rationalized by means of an underlying optimal metabolic design. In this paper we pose a dynamic optimization problem that accounts for time-resource minimization in pathway activation under constrained total enzyme abundance. The optimized variables are time-dependent enzyme concentrations that drive the pathway to a steady state characterized by a prescribed metabolic flux. The problem formulation addresses unbranched pathways with irreversible kinetics. Neither specific reaction kinetics nor fixed pathway length are assumed.
Original languageEnglish
Article number1851
Number of pages22
JournalBulletin of Mathematical Biology
Volume71
Issue number8
Early online date2 May 2009
DOIs
Publication statusPublished - Nov 2009

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