Reactions v11a, v11a2 and v11b form a minimal description for the oxidative phosphorylation, v11b represents the production of ATP, coupled to the flux of protons from the cytosol to the mitochondria
A simplification of the (acetyl-CoA) assimilatory part of the tricarboxylic acid cycle, with implied equilibration of Acetyl-CoA between mitochondria and cytosol
This combined reaction contains the acetyl-CoA synthase (yeast proteins Acs1p and Acs2p, EC 6.2.1.1) which would actually require ATP as a co-substrate (hydrolysed to AMP+PPi)
This combined reaction contains cystathionine β-synthase (yeast protein Cys4p, EC:4.2.1.22) which would require an additional serine as reactant, and cystathionine γ-lyase (yeast protein Cys3p, EC:4.4.1.1) which has oxo-butanoate as an additional product
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. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information. In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not. 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.
proton leakage of the inner mitochondrial membrane, no GO term applicable. The kinetic law is set to 0 as the leakage is handled in reactions v11a, v11a2 and v11b and the proton gradient is assumed to be in equlibrium.
Reactions v11a, v11a2 and v11b form a minimal description for the oxidative phosphorylation, v11a represents the electron transfer from NAD(P)H to the protein complexes of mitochondrial electron transport chain
TODO: NOT CLEAR ABOUT CORRECT VOLUME CORRECTION FOR THIS KINETIC LAW OF A TRANSPORT REACTION
cysteine usage for glutathione and protein synthesis, other pathways and degradation, no GO term applicable
This combined reaction contains phosphoadenylyl-sulfate reductase (thioredoxin) (yeast protein Met16p, EC:1.8.4.8) which also reduces thioredoxin and would actually require an additional NADPH for thioredoxin recovery (reduction), thus a correct stoichiometry would have to include an additional NADPH. This reaction also has adenosine 3',5'-bismonophosphate (PAP) as a product from which the enzyme 3'(2'),5'-bisphosphate nucleotidase (Met22p, EC:3.1.3.7) would revover AMP (and Pi). This latter AMP production is implied in the mass conservation for cytosolic adenosine phosphates (see model notes).
mass conservation for mitochondrial adenosine nucleotides
O-acetyl-homoserine usage for other metabolic reactions, no GO term applicable
A simplification of the oxidative (NADH producing) part of the tricarboxylic acid cycle, with implied equilibration between mitochondrial and cytosolic NADH/NAD+
This reaction (L-homoserine-O-acetyltransferase, Met2p, EC:2.3.1.31) has homoserine as an additional reactant and Coenzyme A as an additional product.
Reactions v11a, v11a2 and v11b form a minimal description for the oxidative phosphorylation, v11b represents the electron transfer from the protein complexes of mitochondrial electron transport chain to oxgyen
mass conservation for cytosolic adenosine nucleotides. This mass conservation is not reflected in the model's stoichiometry directly, but implied by other simplifcations. See model notes for details.
mass conservation for all cellular nicotine amid dinucleotides
mass conservation for mitochondrial TCA enzymes