title: Mathematical modeling of folate metabolism.
abstract: Folate metabolism is a complex biological process that is influenced by many variables including transporters, cofactors, 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 of these models. However, increased complexity does not always lead to increased understanding, and a balanced approach to modeling 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.
authors.affiliation: Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Panetta
authors.forename: Steven W
authors.initials: SW
authors.lastname: Paugh
authors.forename: William E
authors.initials: WE
authors.lastname: Evans
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D004347:Drug Interactions; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D008727:Methotrexate / Q000493:pharmacokinetics / Q000627:therapeutic use; D008962:Models, Theoretical; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy
chemical_list: D018528:ATP-Binding Cassette Transporters; D005492:Folic Acid; D008727:Methotrexate; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010453:Peptide Synthases; C023103:folylpolyglutamate synthetase; C421109:multidrug resistance-associated protein 1