Bhattacharya2014 - A mathematical model of the sterol regulatory element binding protein 2 cholesterol biosynthesis pathway

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Model Identifier
BIOMD0000000890
Short description 
This is a deterministic nonlinear ordinary differential equation mathematical model of the sterol regulatory element binding protein 2 (SREBP-2) cholesterol genetic regulatory pathway in a hepatocyte.
Format
SBML (L2V4)
Related Publication
  • A mathematical model of the sterol regulatory element binding protein 2 cholesterol biosynthesis pathway.
  • Bhattacharya BS, Sweby PK, Minihane AM, Jackson KG, Tindall MJ
  • Journal of theoretical biology , 5/ 2014 , Volume 349 , pages: 150-162 , PubMed ID: 24444765
  • Department of Mathematics and Statistics, University of Reading, Whiteknights, Reading RG6 6AX, UK.
  • Cholesterol is one of the key constituents for maintaining the cellular membrane and thus the integrity of the cell itself. In contrast high levels of cholesterol in the blood are known to be a major risk factor in the development of cardiovascular disease. We formulate a deterministic nonlinear ordinary differential equation model of the sterol regulatory element binding protein 2 (SREBP-2) cholesterol genetic regulatory pathway in a hepatocyte. The mathematical model includes a description of genetic transcription by SREBP-2 which is subsequently translated to mRNA leading to the formation of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), a main regulator of cholesterol synthesis. Cholesterol synthesis subsequently leads to the regulation of SREBP-2 via a negative feedback formulation. Parameterised with data from the literature, the model is used to understand how SREBP-2 transcription and regulation affects cellular cholesterol concentration. Model stability analysis shows that the only positive steady-state of the system exhibits purely oscillatory, damped oscillatory or monotic behaviour under certain parameter conditions. In light of our findings we postulate how cholesterol homeostasis is maintained within the cell and the advantages of our model formulation are discussed with respect to other models of genetic regulation within the literature.
Contributors
Submitter of the first revision: Johannes Meyer
Submitter of this revision: Johannes Meyer
Modellers: Johannes Meyer

Metadata information

hasTaxon (1 statement)
Taxonomy Homo sapiens

hasProperty (2 statements)
Mathematical Modelling Ontology Ordinary differential equation model
NCIt Transcription Factor

Curation status
Curated
Modelling approach(es)
ordinary differential equation model
Tags

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Model files
Bhattacharya2014.xml SBML L2V4 Representation of Bhattacharya2014 - A mathematical model of the sterol regulatory element binding protein 2 cholesterol biosynthesis pathway 30.19 KB Preview | Download

Additional files
Bhattacharya2014.cps COPASI file of Bhattacharya2014 - A mathematical model of the sterol regulatory element binding protein 2 cholesterol biosynthesis pathway 60.24 KB Preview | Download
Bhattacharya2014.sedml SED-ML file of Bhattacharya2014 - A mathematical model of the sterol regulatory element binding protein 2 cholesterol biosynthesis pathway 2.91 KB Preview | Download

  • Model originally submitted by : Johannes Meyer
  • Submitted: Dec 12, 2019 3:22:24 PM
  • Last Modified: Dec 12, 2019 3:23:19 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Dec 12, 2019 3:23:19 PM
    • Submitted by: Johannes Meyer
    • With comment: Automatically added model identifier BIOMD0000000890
  • Version: 1 public model Download this version
    • Submitted on: Dec 12, 2019 3:22:24 PM
    • Submitted by: Johannes Meyer
    • With comment: Import of Bhattacharya2014 - A mathematical model of the sterol regulatory element binding protein 2 cholesterol biosynthesis pathway

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
c

cholesterol 		0.023 item
h

C54701 		1.1E-5 item
m

C54701 		3.65E-8 item
Reactions
Reactions Rate Parameters
=> c; h compartment*mu_c*h mu_c = 0.462
=> h; m compartment*m []
m => compartment*delta_m*m delta_m = 0.00135
c => compartment*delta_c*c delta_c = 0.0036
=> m; c compartment*mu_m/(1+(kappa_m*(1+(c/kappa_c)^y))^x) kappa_m = 1.0E-4; y = 4.0; mu_m = 1.9E-10; x = 3.0; kappa_c = 0.001
h => compartment*delta_h*h delta_h = 0.00193
Curator's comment:
(added: 12 Dec 2019, 15:23:02, updated: 12 Dec 2019, 15:23:02)
Reproduced plot of Figure 3 in the original publication. Model simulated and plot produced using COPASI 4.24 (Build 197).