Mathematical models of the methionine and folate cycles

Paula Grajdeanu (Mathematical Biosciences Institute, The Ohio State University)

(November 3, 2005 10:30 AM - 11:30 AM)

Mathematical models of the methionine and folate cycles


n the study of various aspects of cell metabolism, in particular, folate and methionine metabolism, new mathematical models are developed. The new models are used to to better understand the temporal variations in methionine and folate input on the other metabolite concentrations. Sensitivity analysis of the model is performed to better understand the molecular mechanisms underlying the complexity of the cycles. More specifically, we were interested in how the model qualitative behavior depends on precise choices of parameter values. This is an ongoing work, we finally aim to develop a visualization project, which it will be designed to be used by scientists as testbeds for exploring and evaluating the folate and methionine metabolism. Using advanced computer imaging techniques, the folate cycle and the methionine cycle may be reconstructed from model parameters. The computer reconstructions created through the visualization project will permit cycles to be explored interactively for presentation purposes, while providing an additional modality for data exploration and analysis.

PS 1: The folic acid cycle plays a central role in cell metabolism. Among the important functions of the folate cycle are the synthesis of pyrimidines and purines and the delivery of one carbon units to the methionine cycle for use in methylation reactions. Dietary folate deficiencies as well as mutations in enzymes of the folate cycle are associated with megaloblastic anemia, cancers of the colon, breast and cervix, affective disorders, cleft palate, neural tube defects, Alzheimers disease, Down's syndrome, preeclampsia and early pregnancy loss and several enzymes in the cycle are the targets of anti-cancer drugs.

PS 2: The methionine cycle is important for the regulation of homocysteine, an important risk factor for heart disease, and for the control of DNA methylation. Both hyper- and hypomethylation have been proposed as crucial steps in chains of events that turn normal cells into cancerous cells.