MODEL0911270007
type: SBMLModel
notes: This a model from the article: A theoretical model of type I collagen proteolysis by matrix metalloproteinase (MMP) 2 and membrane type 1 MMP in the presence of tissue inhibitor of metalloproteinase 2. Karagiannis ED, Popel AS. J Biol Chem 2004 Sep 10;279(37):39105-14 15252025 , Abstract: One well documented family of enzymes responsible for the proteolytic processes that occur in the extracellular matrix is the soluble and membrane-associated matrix metalloproteinases. Here we present the first theoretical model of the biochemical network describing the proteolysis of collagen I by matrix metalloproteinases 2 (MMP2) and membrane type 1 matrix metalloproteinases (MT1-MMP) in the presence of the tissue inhibitor of metalloproteinases 2 (TIMP2) in a bulk, cell-free, well stirred environment. The model can serve as a tool for describing quantitatively the activation of the MMP2 proenzyme (pro-MMP2), the ectodomain shedding of MT1-MMP, and the collagenolysis arising from both of the enzymes. We show that pro-MMP2 activation, a process that involves a trimer formation of the proenzyme with TIMP2 and MT1-MMP, is suppressed at high inhibitor levels and paradoxically attains maximum only at intermediate TIMP2 concentrations. We also calculate the conditions for which pro-MMP2 activation is maximal. Furthermore we demonstrate that the ectodomain shedding of MT1-MMP can serve as a mechanism controlling the MT1-MMP availability and therefore the pro-MMP2 activation. Finally the proteolytic synergism of MMP2 and MT1-MMP is introduced and described quantitatively. The model provides us a tool to determine the conditions under which the synergism is optimized. Our approach is the first step toward a more complete description of the proteolytic processes that occur in the extracellular matrix and include a wider spectrum of enzymes and substrates as well as naturally occurring or artificial inhibitors. This model was taken from the CellML repository and automatically converted to …
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parameter: 368847
parameter: 368863
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compartment: 368737
parameter: 368834
parameter: 368921
parameter: 368850
parameter: 368828
rule: 368791
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volume units: volume
name: Karagiannis2004_CollagenIproteolysis
parameter: 368906
parameter: 368809
parameter: 368867
parameter: 368879
rule: 368767
rule: 368773
rule: 368779
parameter: 368831
rule: 368785
parameter: 368891
time units: 577459
units def: 589375
parameter: 368885
curated: false
parameter: 368873
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substance units: 573275
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area units: area
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parameter: 368841
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parameter: 368866
parameter: 368897
parameter: 368857
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parameter: 368844
units def: 589327
parameter: 368860
parameter: 368918
is described by: http://identifiers.org/pubmed/15252025
parameter: 368894
parameter: 368912
parameter: 368837
parameter: 368819
parameter: 368825
parameter: 368870
parameter: 368882
parameter: 368853
parameter: 368876
parameter: 368915
parameter: 368813
parameter: 368909
parameter: 368927
parameter: 368888

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368863
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368828
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368906
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368809
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368867
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368891
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368885
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368900
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name: kon_MT1T2M2p

368838
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368854
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name: kact_M2

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value: 0.0
name: MT1_T2_star

368844
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units: 589291
value: 4.0E-9
name: T2

368860
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value: 3.0E-11
name: M2

368918
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constant: true
units: 589402
value: 3540000.0
name: kon_MT1T2

368894
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constant: true
units: 589375
value: 0.0045
name: kcat_M2C1

368912
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value: 0.00197
name: kcat_MT1C1

368837
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units: 589291
value: 1.0E-8
name: MT1

368819
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name: v6

368825
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units: 589291
value: 1.76E-4
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368882
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name: kiso_M2T2

368853
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name: MT1_T2_M2p

368876
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name: kon_M2T2

368915
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name: kshed_MT1

368813
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units: 589327
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name: v4

368909
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constant: true
units: 589375
value: 9.0E-4
name: koff_MT1T2M2pMT1

368927
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units: 589291
value: 8.5E-6
name: km_MT1C1

368888
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units: 589402
value: 2600.0
name: kon_M2C1

368903
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value: 0.0047
name: koff_MT1T2M2p

368816
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constant: false
units: 589327
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name: v5