Project description:This is an SBML version of the folate cycle model model from:
A mathematical model of the folate cycle: new insights into folate homeostasis.
Nijhout HF, Reed MC, Budu P, Ulrich CM
J. Biol. Chem.,2004, 279
(53),55008-16
pubmedID: 15496403
Abstract:
A mathematical model is developed for the folate cycle based on standard biochemical kinetics. We use the model to provide new insights into several different mechanisms of folate homeostasis. The model reproduces the known pool sizes of folate substrates and the fluxes through each of the loops of the folate cycle and has the qualitative behavior observed in a variety of experimental studies. Vitamin B(12) deficiency, modeled as a reduction in the V(max) of the methionine synthase reaction, results in a secondary folate deficiency via the accumulation of folate as 5-methyltetrahydrofolate (the "methyl trap"). One form of homeostasis is revealed by the fact that a 100-fold up-regulation of thymidylate synthase and dihydrofolate reductase (known to occur at the G(1)/S transition) dramatically increases pyrimidine production without affecting the other reactions of the folate cycle. The model also predicts that an almost total inhibition of dihydrofolate reductase is required to significantly inhibit the thymidylate synthase reaction, consistent with experimental and clinical studies on the effects of methotrexate. Sensitivity to variation in enzymatic parameters tends to be local in the cycle and inversely proportional to the number of reactions that interconvert two folate substrates. Another form of homeostasis is a consequence of the nonenzymatic binding of folate substrates to folate enzymes. Without folate binding, the velocities of the reactions decrease approximately linearly as total folate is decreased. In the presence of folate binding and allosteric inhibition, the velocities show a remarkable constancy as total folate is decreased.
This model was encoded by Michal Galdzicki from a MatLab file send to him by Prof. Michael Reed. There some differences in this model compared to the one described in the article, possible due to typos in the publication:
1) reaction NE (THF + H2CO 5,10-CH2-THF) in the article has H2C=O as a
reactant and is mentioned to display pseudo first order mass action
kinetics, while in the matlab file formic acid, also used in reaction FTS, is included in the rate law for the forward reaction.
2) the reaction MS is modeled after Reed et al. 2004, which is not
explicitly mentioned in the article, although Kd and the parameters
from Reed et al. 2004 are given.
3) in the kinetic law of the SHTM reaction (THF + Ser
5,10-CH2-THF + Gly), there are separate values given for Km,Gly
and Km,5,10-CH2-THF in the article. in the matlab file and the SBML
model Km,Ser and Km,THF are used instead of Km,Gly and Km,5,10-CH2-THF
for the backwards reaction.
To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication
for more information.
In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.
To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.
2009-03-25 | BIOMD0000000213 | BioModels
Michal Galdzicki 
