Lambeth, Kushmerick, 2002

Model Status

This is the original unchecked version of the model imported from the previous CellML model repository, 24-Jan-2006.

Model Structure

Glycogenolysis is the chemical breakdown of glycogen, the storage form of glucose present in the liver and in muscle. It can be regarded as an extension of the glycolysis pathway, in which simple glucose sugars are broken down during metabolism. The enzyme constituents, and their kinetic properties, have been well characterised for glycolysis. Historically, mathematical modelling efforts have been focused on erythrocytes (red blood cells) (Metabolism in the Human Erythrocyte, Mulquiney and Kuchel, 1999), the fungus yeast (The Glycolytic Metabolic Pathway in the Yeast Saccharomyces cerevisiae, 1997), and the parasite T. brucei (Modelling Glycolysis in Trypanosoma brucei, Bakker et al., 1997). These studies have produced one common finding. It seems that flux through the glycolysis pathway is controlled by different mechanisms in different cell types. This has lead to the suggestion that the control of pathway flux may be more dependent on the general cell properties, rather than on the specific properties of the enzymes within the pathway.

In their 2002 mathematical model described here, Melissa Lambeth and Martin Kushmerick are looking to better understand the role of glycogenolysis and glycolytic fluxes in skeletal muscle metabolism. The mathematical modelling of glycolysis in muscle has not been studied in depth since the initial efforts of Garfinkel et al. in 1968. It is made difficult by a number of factors, including:

• the large range of fluxes (0.6-60 mM ATP/min);

• large changes in metabolite concentrations (lactate, inorganic phosphate and phosphocreatine) due to differing muscle properties and fluctuating intensity and duration of activity;

• uncertainty in the kinetic function and substrate concentration in the glycogen phosphorylase reaction; and

• lack of agreement over the control mechanisms that regulate flux.

Using mammalian kinetic parameters obtained from the literature, Lambeth and Kushmerick developed a dynamic model of the glycogenolytic pathway, from glycogen to lactate, in skeletal muscle (see the figure below). To this basic model of 12 rate equations, they added additional reactions important for muscle energetics. The glycolytic pathway represented by this model is considered to be an isolated pathway that does not interact with other metabolites, reactions, or pathways. It is a continuum model based on standard differential equations, with metabolite fluxes calculated based on reaction kinetics (Michaelis-Menten enzyme kinetics are used). The model features stoichiometric constraints, mass balance, and reversible thermodynamics as defined by the Haldane relation.

The complete original paper reference is cited below:

A Computational Model for Glycogenolysis in Skeletal Muscle, Melissa J. Lambeth and Martin J. Kushmerick, 2002, Annals of Biomedical Engineering , 30, 808-827. (Full text and PDF versions of the article are available to subscribers on the journal website.) PubMed ID: 12220081

A schematic diagram of the reactions used in the model of the glycogenolysis pathway in skeletal muscle.