The control systems structures of energy metabolism

Abstract

The biochemical regulation of energy metabolism (EM) allows cells to modulate their energetic output depending on available substrates and requirements. To this end, numerous biomolecular mechanisms exist that allow the sensing of the energetic state and corresponding adjustment of enzymatic reaction rates. This regulation is known to induce dynamic systems properties such as oscillations or perfect adaptation. Although the various mechanisms of energy regulation have been studied in detail from many angles at the experimental and theoretical levels, no framework is available for the systematic analysis of EM from a control systems perspective. In this study, we have used principles well known in control to clarify the basic system features that govern EM. The major result is a subdivision of the biomolecular mechanisms of energy regulation in terms of widely used engineering control mechanisms: proportional, integral, derivative control, and structures: feedback, cascade and feed-forward control. Evidence for each mechanism and structure is demonstrated and the implications for systems properties are shown through simulations. As the equivalence between biological systems and control components presented here is generic, it is also hypothesized that our work could eventually have an applicability that is much wider than the focus of the current study.

The relationship of glycerol and glycolysis metabolism patway under hyperosmotic stress in Dunaliella salina

“…Glycerol-3-P is then converted into glycerol by glycerol-3-phosphate phosphatase (GPP). PFK is a key regulatory enzyme early in the glycolytic pathway [24]. Alhough many studies have examined PFK in plants and animals, PFK in algae remains poorly understood.…”

Animal Models of Parkinson's Disease: Vertebrate Genetics

“…Diverse approaches and tools used in human studies can similarly be applied to characterize animal models in detail. For example, application of new methods in expression profiling, proteomics, and metabolomics can be used for detailed characterization of PD mouse models, thus providing a global network assessment of pathogenic pathways in a controlled physiological environment with the same genetic background (Simunovic et al 2009;Cloutier and Wellstead 2010).…”

Synthetic biology and regulatory networks: where metabolic systems biology meets control engineering

“…It includes (i) the use of feedback control in the design and realization of synthetic gene-metabolic systems, including the implementation of biological sensors, controllers and actuators, (ii) the clarification of different metabolic or genetic regulatory mechanisms in terms of widely used control mechanisms [35,77], (iii) attenuation of the retroactivity, crosstalk and noise effects when interconnecting synthetic modules by introducing feedback loops around modules, and (iv) identification of the design constraints and of the existence of local stability in terms of design parameters such as promoter and ribosome characteristics.…”

“…This may ensure the robustness versus perturbations at various frequencies as widely considered in engineering system design. It has been shown [35,77,123] that metabolic regulation through allosteric or more direct substrate-product effects is related to a 'proportional or nonlinear control' action, because the catalytic activity of an enzyme can depend on a metabolite concentration in a proportional or nonlinear kinetic relationship. The metabolic regulation often acts as a fast actuator/controller that rapidly buffers against highfrequency perturbations but possibly with small amplitude or capability, such as adaptation to small fluctuations in the flux demand [86].…”

“…For example, three classical control mechanisms known in control engineering, i.e. proportional, integral and derivative control, have been identified in the regulation of energy metabolism in living organisms [35]. In addition, the closed-loop feedback control principle has been used to design both genetically encoded (RNA or protein) biosensors that help optimize and regulate heterologous pathways [36] and a sensor-regulator system that improves fatty acidbased biodiesel production [37].…”