Integrative Modeling of Oxidative Stress and C1 Metabolism Reveals Upregulation of Formaldehyde and Downregulation of Glutathione

This research provides the first integrative model of oxidative stress and C1 metabolism in plants. The complexity of molecular pathway systems of oxidative stress is modeled and then integrated with a previously developed in silico model of C1 metabolism system. This molecular systems integration provides two important results: demonstration of the scalability of the CytoSolve Collaboratory and derivation of new insights on the effects of oxidative stress on C1 metabolism relative to formaldehyde (HCHO). The results from this research of integrative oxidative stress with C1 metabolism, however, demonstrate significant upregulation of HCHO concentrations, with concomitant downregulation and depletion of glutathione. Sensitivity analysis indicates that kGSH-HCHO, the rate constant of GSH-HCHO binding, VSHMT, the rate of formation of sarcosine from glycine, and ..., the rate of superoxide formation significantly affect HCHO homeostasis in the C1 metabolism. Future research may employ this integrative model to explore which conditions initiate oxidative stress and the resultant upregulation and downregulation of HCHO and glutathione. (ProQuest: ... denotes formulae/symbols omitted.)