049687
constant: false
units: 899054
value: NaN
name: v4
type: Parameter

049745
constant: false
units: 899016
value: 0.0
name: M9_T1_M3
type: Parameter

049697
constant: false
units: 899054
value: NaN
name: v9
type: Parameter

899102
unit: 899114
name: first_order_rate_constant
type: SBMLUnitsDef

049731
constant: false
units: 899016
value: 0.0
name: pM9_T1
type: Parameter

MODEL7888000034
parameter: 049731
is described by: http://identifiers.org/pubmed/17848556
parameter: 049691
substance units: 106194
parameter: 049699
units def: 899102
parameter: 049779
parameter: 049775
rule: 049631
rule: 049621
parameter: 049707
parameter: 049717
rule: 049629
rule: 049619
parameter: 049759
parameter: 049721
rule: 049654
parameter: 049685
rule: 049644
rule: 049678
rule: 049668
parameter: 049769
parameter: 049747
parameter: 049695
parameter: 049813
parameter: 049771
notes: This is the model described in the article: A biochemical model of matrix metalloproteinase 9 activation and inhibition. Vempati P, Karagiannis ED, Popel AS. J Biol Chem. 2007 Dec 28;282(52):37585-96. Pubmed ID: 17848556 , doi: 10.1074/jbc.M611500200 . Abstract: Matrix metalloproteinases (MMPs) are a class of extracellular and membrane-bound proteases involved in an array of physiological processes, including angiogenesis. We present a detailed computational model of MMP9 activation and inhibition. Our model is validated to existing biochemical experimental data. We determine kinetic rate constants for the processes of MMP9 activation by MMP3, MMP10, MMP13, and trypsin; inhibition by the tissue inhibitors of metalloproteinases (TIMPs) 1 and 2; and MMP9 deactivation. This computational approach allows us to investigate discrepancies in our understanding of the interaction of MMP9 with TIMP1. Specifically, we find that inhibition due to a single binding event cannot describe MMP9 inhibition by TIMP1. Temporally accurate biphasic inhibition requires either an additional isomerization step or a second lower affinity isoform of MMP9. We also theoretically characterize the MMP3/TIMP2/pro-MMP9 and MMP3/TIMP1/pro-MMP9 systems. We speculate that these systems differ significantly in their time scales of activation and inhibition such that MMP9 is able to temporarily overshoot its final equilibrium value in the latter. Our numerical simulations suggest that the ability of pro-MMP9 to complex TIMP1 increases this overshoot. In all, our analysis serves as a summary of existing kinetic data for MMP9 and a foundation for future models utilizing MMP9 or other MMPs under physiologically well defined microenvironments. This model was taken from the CellML repository and automatically converted to SBML. The original model is: Vempati, Karagiannis, Popel, 2007 version 1 The original CellML model was created and curated by: Catherine May Lloyd c.lloyd(at)auckland.ac.nz The University o…
rule: 049637
units def: 899126
parameter: 049807
parameter: 049795
parameter: 049703
parameter: 049713
parameter: 049803
parameter: 049755
parameter: 049749
parameter: 049733
parameter: 049727
parameter: 049737
parameter: 049751
units def: 899016
parameter: 049693
parameter: 049741
rule: 049615
rule: 049650
rule: 049640
rule: 049611
rule: 049609
parameter: 049761
parameter: 049789
rule: 049674
rule: 049664
parameter: 049785
parameter: 049719
parameter: 049723
parameter: 049687
volume units: metaid_0000217
parameter: 049817
rule: 049633
rule: 049623
rule: 049656
rule: 049646
rule: 049670
area units: area
rule: 049605
name: Vempati2007_MMP9_Regulation
parameter: 049781
parameter: 049797
type: SBMLModel
compartment: 049601
parameter: 049809
parameter: 049757
parameter: 049735
parameter: 049729
parameter: 049739
rule: 049660
parameter: 049765
parameter: 049683
parameter: 049743
parameter: 049787

049741
constant: false
units: 899016
value: 0.0
name: pM9_T1_M3
type: Parameter

049797
constant: true
units: 899102
value: 0.007
name: koff_TrpM9T1
type: Parameter

049735
constant: false
units: 899016
value: 0.0
name: M9_T1_star
type: Parameter

049749
constant: false
units: 899016
value: 0.0
name: Tr_pM9
type: Parameter

899054
unit: 899090
unit: 899078
unit: 899066
name: flux
type: SBMLUnitsDef

049680
constant: false
units: 899054
value: NaN
name: v1
type: Parameter

049601
constant: true
units: litre
size: 1.0
spatial dimensions: 3.0
type: Compartment

049721
constant: false
units: 899016
value: 3.0E-7
name: pM9
type: Parameter

899163
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

049683
constant: false
units: 899054
value: NaN
name: v2
type: Parameter

049711
constant: false
units: 899054
value: NaN
name: v16
type: Parameter

049793
constant: true
units: 899102
value: 0.007
name: koff_TrpM9
type: Parameter

899016
unit: 899041
unit: 899029
name: molar
type: SBMLUnitsDef

049707
constant: false
units: 899054
value: NaN
name: v14
type: Parameter

049783
constant: true
units: 899102
value: 6.3E-4
name: kon_M9T1
type: Parameter

049703
constant: false
units: 899054
value: NaN
name: v12
type: Parameter

049763
constant: true
units: 899126
value: 10000.0
name: kon_M3pM9
type: Parameter

049777
constant: true
units: 899102
value: 1.26E-4
name: koff_M3T1
type: Parameter

049819
constant: true
units: 899102
value: 0.0019
name: kact_M3pM9
type: Parameter

049693
constant: false
units: 899054
value: NaN
name: v7
type: Parameter

049713
constant: false
units: 899054
value: NaN
name: v17
type: Parameter

049801
constant: true
units: 899102
value: 0.007
name: koff_TrpM9T1M3
type: Parameter

049717
constant: false
units: 899054
value: NaN
name: v19
type: Parameter

049753
constant: false
units: 899016
value: 0.0
name: Tr_pM9_T1_M3
type: Parameter

049809
constant: true
units: 899102
value: 5.7E-4
name: kact_M3pM9T1M3
type: Parameter

899126
unit: 899163
unit: 899150
unit: 899138
name: second_order_rate_constant
type: SBMLUnitsDef

049787
constant: true
units: 899126
value: 1900000.0
name: kon_M3_pM9T1
type: Parameter

049737
constant: false
units: 899016
value: 0.0
name: M9
type: Parameter

049815
constant: true
units: 899102
value: 6.0E-4
name: kact_TrpM9T1
type: Parameter

049773
constant: true
units: 899102
value: 0.001
name: koff_M3pM9T1M3
type: Parameter

049727
constant: false
units: 899016
value: 3.0E-7
name: T1
type: Parameter

049767
constant: true
units: 899126
value: 10000.0
name: kon_M3pM9T1
type: Parameter

899078
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

049805
constant: true
units: 899126
value: 34000.0
name: koff_M9_M3T1
type: Parameter

049811
constant: true
units: 899102
value: 1.26E-4
name: kact_M9T1M3
type: Parameter

049757
constant: true
units: 899102
value: 7.48E-5
name: koff_pM9T1
type: Parameter

899090
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

899041
exponent: -1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

049689
constant: false
units: 899054
value: NaN
name: v5
type: Parameter

049747
constant: false
units: 899016
value: 1.0E-7
name: Tr
type: Parameter

899066
exponent: 1.0
scale: 0
multipler: 1.0
kind: MOLE
type: SBMLUnit

049795
constant: true
units: 899126
value: 10000.0
name: kon_TrpM9T1
type: Parameter

049799
constant: true
units: 899126
value: 10000.0
name: kon_TrpM9T1M3
type: Parameter

899150
exponent: 1.0
scale: 0
multipler: 1.0
kind: LITRE
type: SBMLUnit

049699
constant: false
units: 899054
value: NaN
name: v10
type: Parameter

049733
constant: false
units: 899016
value: 0.0
name: M3_pM9_T1
type: Parameter

049685
constant: false
units: 899054
value: NaN
name: v3
type: Parameter

899114
exponent: -1.0
scale: 0
multipler: 1.0
kind: SECOND
type: SBMLUnit

049743
constant: false
units: 899016
value: 0.0
name: M3_pM9_T1_M3
type: Parameter

049723
constant: false
units: 899016
value: 5.0E-8
name: M3
type: Parameter

049695
constant: false
units: 899054
value: NaN
name: v8
type: Parameter

049779
constant: true
units: 899126
value: 5600000.0
name: kon_M9T1_star
type: Parameter

049803
constant: true
units: 899102
value: 7.48E-5
name: kon_M9_M3T1
type: Parameter

049701
constant: false
units: 899054
value: NaN
name: v11
type: Parameter

899138
exponent: -1.0
scale: 0
multipler: 1.0
kind: MOLE
type: SBMLUnit

049715
constant: false
units: 899054
value: NaN
name: v18
type: Parameter

049781
constant: true
units: 899102
value: 1.6E-5
name: koff_M9T1_star
type: Parameter

049817
constant: true
units: 899102
value: 6.0E-4
name: kact_TrpM9T1M3
type: Parameter

049691
constant: false
units: 899054
value: NaN
name: v6
type: Parameter

049705
constant: false
units: 899054
value: NaN
name: v13
type: Parameter

049791
constant: true
units: 899126
value: 10000.0
name: kon_TrpM9
type: Parameter

899029
exponent: 1.0
scale: 0
multipler: 1.0
kind: MOLE
type: SBMLUnit

049771
constant: true
units: 899126
value: 10000.0
name: kon_M3pM9T1M3
type: Parameter

049751
constant: false
units: 899016
value: 0.0
name: Tr_pM9_T1
type: Parameter

049719
constant: false
units: 899054
value: NaN
name: v20
type: Parameter

049789
constant: true
units: 899102
value: 1.26E-4
name: koff_M3_pM9T1
type: Parameter

049725
constant: false
units: 899016
value: 0.0
name: M3_pM9
type: Parameter

049785
constant: true
units: 899102
value: 2.5E-4
name: koff_M9T1
type: Parameter

049739
constant: false
units: 899016
value: 0.0
name: M9_T1
type: Parameter

049813
constant: true
units: 899102
value: 0.002
name: kact_TrpM9
type: Parameter

049755
constant: true
units: 899126
value: 34000.0
name: kon_pM9T1
type: Parameter

049769
constant: true
units: 899102
value: 0.001
name: koff_M3pM9T1
type: Parameter

049729
constant: false
units: 899016
value: 0.0
name: M3_T1
type: Parameter

049759
constant: true
units: 899126
value: 34000.0
name: kon_pM9T1M3
type: Parameter

049709
constant: false
units: 899054
value: NaN
name: v15
type: Parameter

049765
constant: true
units: 899102
value: 0.001
name: koff_M3pM9
type: Parameter

049807
constant: true
units: 899102
value: 5.7E-4
name: kact_M3pM9T1
type: Parameter

049761
constant: true
units: 899102
value: 7.48E-5
name: koff_pM9T1M3
type: Parameter

049775
constant: true
units: 899126
value: 1900000.0
name: kon_M3T1
type: Parameter