Modulation of a Metabolic Network by Cytoskeletal Organisation and Dynamics |  PDF |
Catherine Lloyd (Bioengineering Institute, University of Auckland)
Table of Contents
The spatio-temporal coordination of cellular processes is a challenge which is faced by many biological systems, including cell growth, proliferation, differentiation, and functional adaptation. Such coordination is apparent in processes such as signal transduction, gene expression, and metabolism. Over the past few decades, two main theories concerning the organisation of metabolism have evolved:
The concept of metabolic channelling, where reactions are facilitated by substrate transfer between closely associated enzymes; and
The idea of cytoskeletal driven control of enzyme fluxes.
Although these two theories are not mutually exclusive, there are cases where one mechanism will be favoured over the other, for example, channelling would not be favoured on the surface of a supramolecular structure.
The microtubular protein enhancement of metabolic flux depends on several factors, including:
The concentration of the microtubular protein;
The presence of microtubule associated proteins (MAPs);
The polymerisation state of the cytoskeletal proteins; and
The type of cytoskeletal protein present.
The cellular metabolic response to hormones such as insulin and glucagon depends on cell volume: turgid cells synthesise protein and glycogen, whereas flaccid cells break down these substances. Cytoskeletal dynamics play an essential role in sensing and responding to osmotic stress. It is likely that the spatial organisation and orientation of cytoskeletal proteins are modulating gene expression, signal transduction, and metabolic fluxes. Microtubules, actin microfilaments, and intermediate filaments represent a large surface area in the cell (estimated to be 3000 micrometres square per mammalian cell). This large surface area provides an interface for enzyme and other protein binding.
Although much is known about the interactions between glycolytic enzymes and cytoskeletal proteins, much less is understood about the consequences of these interactions. In their 2002 mathematical model of cytoskeletal modulation of a metabolic network, Miguel Aon and Sonia Cortassa look to determine the influence of cytoskeletal organisation and dynamics on cellular biochemistry. Specifically, they address the question of whether the degree of microtubule polymerisation affects the metabolic flux through the glycolytic pathway and/or it branches towards the pentose phosphate cycle, the tricarboxylic acid (TCA) cycle, and ethanol fermentation. Their model (see Figure 1 below) is based on experimental data from yeast.
The main observation taken from the model simulations was that the cytoskeleton provides the modulation of metabolism with coherence (the integration of diverse elements and activities to produce a consistent response) and robustness (enhanced stability in the steady state dynamic behaviour of the metabolic network when parameters are varied).
The model has been described here in CellML (the raw CellML description of the Aon and Cortassa model can be downloaded in various formats as described in the section “Download This Model”).
The complete original paper reference is cited below:
Coherent and robust modulation of a metabolic network by cytoskeletal organization and dynamics, Miguel A. Aon and Sonia Cortassa, 2002, Biophysical Chemistry, 97, 213-231. (Full text (HTML) and PDF versions of the article are available on the Biophysical Chemistry website.) PubMed ID: 12050011
aon_model_2002.xml — the raw XML.
aon_model_2002.html — an HTML version for browsing online.
aon_model_2002.pdf — a PDF version suitable for printing.
cellml_aon_model_2002.tar.gz — a gzipped tarball with the XML and this documentation.
aon_model_2002_maths.pdf — a PDF of the equations described in the model generated directly from the CellML description using the MathML Renderer.
