Mathematical analysis of a mechanism for autonomous metabolic oscillations in continuous culture of Saccharomyces cerevisae

Model Structure

Cellular oscillations are appropriate for investigating the structure and regulatory properties of biochemical networks. Whilst calcium dynamics and glycolytic oscillations have been intensively studied (see The Wolf et al. Mathematical Model of Glycolytic Oscillations in yeast, 2000), autonomous metabolic oscillations are a relatively new field. In their 2001 study, Jana Wolf, Ho-Yong Sohn, Reinhart Heinrich and Hiroshi Kuriyama observed autonomous metabolic oscillations in aerobic continuous cultures of Saccharomyces cerevisiae. Experimental investigation of the underlying mechanisms revealed that several pathways and regulatory couplings are involved. The authors translate a hypothetical mechanism including the sulphate assimilation pathway, ethanol degradation and respiration into a mathematical model. Simulations confirm the ability of the model to produce limit cycle oscillations which reproduce most of the characteristic features of the system.

The model includes the pathways which were found to be essential for the generation of oscillations. These are the synthesis of the amino acid cysteine by the sulfate assimilation pathway, the uptake and degradation of the carbon source ethanol, the citrate cycle and oxidative phosphorylation. Only regulatory couplings which are critical for the oscillations are considered, including the inhibitory effect of cysteine on the sulfate uptake and the inhibition of the respiratory chain by sulphide (the reaction network of the model is shown below in the figure ).

The complete original paper reference is cited below:

Mathematical analysis of a mechanism for autonomous metabolic oscillations in continuous culture of Saccharomyces cerevisiae , Jana Wolf, Ho-Yong Sohn, Reinhart Heinrich and Hiroshi Kuriyama, 2001, FEBS Letters , 499, 230-234. (The PDF and full text versions of the article are available to subscribers on the Science Direct website.) PubMed ID: 11423122

The raw CellML description of the model can be downloaded in various formats as described in .

Reaction scheme of the model. The following abbreviations are introduced for the metabolites: sul: sulphate ions, aps: adenylyl sulfate, pap: 3-phosphoadenylyl sulfate, hyd: hydrogen sulphide, cys: cysteine, eth: ethanol, aco: acetyl-CoA, S1 and S2: intermediates of the citric acid cycle, oxy: oxygen, C1 and C2: protein complexes involved in oxidative phosphorylation, A3: ATP, A2: ADP, N1: NAD(P)+, N2: NAD(P)H, oah: O-acetylhomoserine. The cytosolic and mitochondrial compartments are characterized by the superscripts c and m, respectively.