The 5-formyltetrahydrofolate futile cycle reduces pathway stochasticity in an extended hybrid-stochastic model of folate-mediated one-carbon metabolism.

ABSTRACT: In folate-mediated one-carbon metabolism (FOCM), 5-formyltetrahydrofolate (5fTHF), a one-carbon substituted tetrahydrofolate (THF) vitamer, acts as an intracellular storage form of folate and as an inhibitor of the folate-dependent enzymes phosphoribosylaminoimidazolecarboxamide formyltransferase (AICARFT) and serine hydroxymethyltransferase (SHMT). Cellular levels of 5fTHF are regulated by a futile cycle comprising the enzymes SHMT and 5,10-methenyltetrahydrofolate synthetase (MTHFS). MTHFS is an essential gene in mice; however, the roles of both 5fTHF and MTHFS in mammalian FOCM remain to be fully elucidated. We present an extension of our previously published hybrid-stochastic model of FOCM by including the 5fTHF futile-cycle to explore its effect on the FOCM network. Model simulations

SUBMITTER: Misselbeck K 

PROVIDER: S-EPMC6416297 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature