Mathematical modeling of folate metabolism

Abstract

Folate metabolism is a complex biological process that is influenced by many variables including transporters, co-factors and enzymes. Mathematical models provide a useful tool to evaluate this complex system and to elucidate hypotheses that would be otherwise untenable to test in vitro or in vivo. Forty years of model development and refinement along with enhancements in technology have led to systematic improvement in our biological understanding from these models. However, increased complexity does not always lead to increased understanding, and a balanced approach to modelling the system is often advantageous. This approach should address questions about sensitivity of the model to variation and incorporate genomic data. The folate model is a useful platform for investigating the effects of antifolates on the folate pathway. The utility of the model is demonstrated through interrogation of drug resistance, drug-drug interactions, drug selectivity, and drug doses and schedules. Mathematics can be used to create models with the ability to design and improve rationale therapeutic interventions.

Automatic biosystems comparison using semantic and name similarity

“…We choose here 3 of them to study their similarity. We have: the folate cycle model with Biomodels ID BIOMD0000000018, the Folate Cycle with Biomodels ID BIOMD0000000213 that are integrated in the one carbon glutathione metabolism with Biomodels ID BIOMD0000000268 [11,24].…”

Heuristic parallelizable algorithm for similarity based biosystems comparison

“…We choose here 3 of them to study their similarity. We have: the folate cycle model with Biomodels ID BIOMD0000000018, the folate cycle with Biomodels ID BIOMD0000000213 that are integrated in the one carbon glutathione metabolism with Biomodels ID BIOMD0000000268 [27,32].…”

Rat liver folate metabolism can provide an independent functioning of associated metabolic pathways

“…Mathematical modeling is a powerful tool for analysis of complex metabolic systems 14–17 . Several previously developed mathematical models of folate metabolism were aimed at understanding the mechanism of methotrexate action in cancer cells and optimization of antitumor therapy 18–24 or describing folate metabolism in microorganisms with the goal of developing new antifolate drugs 25 . The most extensive modeling of folate metabolism and its connection with other metabolic systems in animal cells was performed in a series of studies published by Nijhout, Reed, and coauthors 26–31 .…”