Wiley Interdiscip Rev Syst Biol Med - Modeling cellular compartmentation in one-carbon metabolism.

Tópicos

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Resumo

Folate-mediated one-carbon metabolism (FOCM) is associated with risk for numerous pathological states including birth defects, cancers, and chronic diseases. Although the enzymes that constitute the biological pathways have been well described and their interdependency through the shared use of folate cofactors appreciated, the biological mechanisms underlying disease etiologies remain elusive. The FOCM network is highly sensitive to nutritional status of several B-vitamins and numerous penetrant gene variants that alter network outputs, but current computational approaches do not fully capture the dynamics and stochastic noise of the system. Combining the stochastic approach with a rule-based representation will help model the intrinsic noise displayed by FOCM, address the limited flexibility of standard simulation methods for coarse-graining the FOCM-associated biochemical processes, and manage the combinatorial complexity emerging from reactions within FOCM that would otherwise be intractable.

Resumo Limpo

folatemedi onecarbon metabol focm associ risk numer patholog state includ birth defect cancer chronic diseas although enzym constitut biolog pathway well describ interdepend share use folat cofactor appreci biolog mechan under diseas etiolog remain elus focm network high sensit nutrit status sever bvitamin numer penetr gene variant alter network output current comput approach fulli captur dynam stochast nois system combin stochast approach rulebas represent will help model intrins nois display focm address limit flexibl standard simul method coarsegrain focmassoci biochem process manag combinatori complex emerg reaction within focm otherwis intract

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