MODEL7888000034
type: SBMLModel
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
rule: 049644
parameter: 049685
area units: area
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
rule: 049605
name: Vempati2007_MMP9_Regulation
parameter: 049781
parameter: 049797
compartment: 049601
parameter: 049809
parameter: 049757
parameter: 049735
parameter: 049729
parameter: 049739
rule: 049660
parameter: 049765
parameter: 049683
parameter: 049743
parameter: 049787

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

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

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

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

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

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

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

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

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

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

899102
type: SBMLUnitsDef
unit: 899114
name: first_order_rate_constant

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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