Project description:This model by Jana Wolf et al. 2001 is the first mechanistic model of respiratory oscillations in Saccharomyces cerevisae. It is based on the assumption that feedback inhibition of cysteine on the sulfate transporters leads to oscillations in this pathway and causes oscillations in respiratory activity via inhibition of cytochrome c oxidase by hydrogen disulfide. The model is qualitative/semi-quantitative and reproduces the respiratory oscillation pattern quite well. It is based on very coarse-grained representations of the mitochondrial tricarboxylic acid cycle and the mitochondrial electron transport chain (oxidative phosphorylation). The sulfate assimilatory pathways also contains some significant simplifcations.
The model corresponds to Fig. 2B of the paper, with a slight phase shift of the oscillations. No initial conditions were given in the paper, and thus they were chosen arbitrarily in a range that lies within the basin of attraction of the limit cycle oscillations. Species IDs correspond to IDs used by the authors, while SBML names are more common abbreviations.
Caveats:
1) Equilibrated transport:
The model assumes fast equilibration between mitochondria and cytoplasm for the metabolites NADH, NAD+, H2S and Acetyl-CoA.
2) Cytosolic mass conservation ATP/ADP:
The model uses mass conservation for cytosolic adenosine nucleotides with is however not encoded in the stoichiometry, but is implied by the lumped reaction v4. This reaction combines the enzymatic reactions of phosphoadenylyl-sulfate reductase (thioredoxin) (yeast protein Met16p, EC 1.8.4.8) and sulfite reductase (NADPH) (subunits Met5p and Met10p, EC 1.8.1.2). EC 1.8.4.8 also has adenosine-3',5'-bismonophosphate (PAP, not to confuse with ID pap in this model, standing for PAPS) as a product. PAP is the substrate for enzyme 3'(2'),5'-bisphosphate nucleotidase (Met22p, EC:3.1.3.7) which would revover AMP (and Pi). Then AMP can be assumed to be equilibrated with ATP and ADP via adenylate kinase, as often used in metabolic models. This AMP production is implied in the mass conservation for cytosolic adenosine phosphates. Accounting for these reactions explicitly does not change the dynamics of the model significantly. An according version can be obtained from the SBML creator (Rainer Machne, mailto:raim@tbi.univie.ac.at).
3) Redox balance:
The enzyme sulfite reductase (NADPH) (subunits Met5p and Met10p, EC 1.8.1.2, part of reaction v4) actually uses NADPH, and the authors assume equilibration of NADH and NADPH. But actually S. cerevisiae specifically is missing the according enzyme transhydrogenase (EC 1.6.1.1 or EC 1.6.1.2). EC 1.8.4.8 also oxidizes thioredoxin and would actually require an additional NADPH for thioredoxin recovery (reduction). This would slightly affect the redox balance of the model.
4) Energy balance:
Reaction v7 lumps NAD-dependent alcohol dehydrogenase (EC 1.1.1.1), aldehyde dehydrogenase (NAD+) (EC 1.2.1.3) and acetyl-CoA synthase (EC 6.2.1.1). The latter reaction would actually consume ATP as a co-factor, producing AMP+PPi, and this is not included in the model. This would slightly bias the model's energy balance.
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To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2024-09-02 | BIOMD0000000090 | BioModels
Lukas Endler 
