metaid_0000012
is version of: C07946
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000007
name: lytic_BoNT/A
type: Species

metaid_0000016
kinetic law: 930319
product: 930306
reactant: 930294
is version of: REACT 11085.1
fast: false
reversible: false
type: Reaction

930257
stoichiometry: 1.0
species: metaid_0000010
type: SpeciesReference

930209
exponent: 1.0
scale: 0
multipler: 1.0
kind: DIMENSIONLESS
type: SBMLUnit

990536
units: metaid_0000022
value: 0.141
type: LocalParameter

metaid_0000006
is: GO:0031904
constant: true
size: 1.0
spatial dimensions: 3.0
name: endosome
type: Compartment

930331
stoichiometry: 1.0
species: metaid_0000009
type: SpeciesReference

930368
stoichiometry: 1.0
species: metaid_0000008
type: SpeciesReference

metaid_0000011
has part: C07946
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000006
name: transloc_BoNT/A
type: Species

930245
exponent: -1.0
scale: 0
multipler: 60.0
kind: SECOND
type: SBMLUnit

metaid_0000015
kinetic law: 930281
product: 930269
reactant: 930257
is homolog to: REACT 11086.1
fast: false
reversible: false
type: Reaction

930344
stoichiometry: 1.0
species: metaid_0000010
type: SpeciesReference

metaid_0000019
unit: 930209
name: relative concentration
type: SBMLUnitsDef

metaid_0000009
is: C07946
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000005
name: free_BoNT/A
type: Species

metaid_0000020
unit: 930221
name: normalized volume
type: SBMLUnitsDef

930221
exponent: 1.0
scale: 0
multipler: 1.0
kind: DIMENSIONLESS
type: SBMLUnit

metaid_0000005
is: GO:0005615
constant: true
size: 1.0
spatial dimensions: 3.0
name: extracellular
type: Compartment

metaid_0000004
is: C07946
constant: false
boundary condition: true
has only substance units: false
initial concentration: NaN
initial amount: NaN
in compartment: metaid_0000005
name: tot_free_BoNT/A
type: Species

930306
stoichiometry: 1.0
species: metaid_0000012
type: SpeciesReference

BIOMD0000000178
type: SBMLModel
curated: true
rule: metaid_0000014
length unit: length
occurs in: http://identifiers.org/taxonomy/10116
is version of: GO:0009405
name: Lebeda2008_BoTN_Paralysis_4stepModel
creator:
  ORG:
    orgname: Integrated Toxicology Division, US Army Medical Research Institute of Infectious Diseases
  n:
    given: Frank
    family: Lebeda
is version of: GO:0006898
is version of: GO:0033264
is derived from: BIOMD0000000267
notes: This model is the 4-step model from the article: Onset dynamics of type A botulinum neurotoxin-induced paralysis. Lebeda FJ, Adler M, Erickson K, Chushak Y J Pharmacokinet Pharmacodyn 2008 Jun; 35(3): 251-67 18551355 , Abstract: Experimental studies have demonstrated that botulinum neurotoxin serotype A (BoNT/A) causes flaccid paralysis by a multi-step mechanism. Following its binding to specific receptors at peripheral cholinergic nerve endings, BoNT/A is internalized by receptor-mediated endocytosis. Subsequently its zinc-dependent catalytic domain translocates into the neuroplasm where it cleaves a vesicle-docking protein, SNAP-25, to block neurally evoked cholinergic neurotransmission. We tested the hypothesis that mathematical models having a minimal number of reactions and reactants can simulate published data concerning the onset of paralysis of skeletal muscles induced by BoNT/A at the isolated rat neuromuscular junction (NMJ) and in other systems. Experimental data from several laboratories were simulated with two different models that were represented by sets of coupled, first-order differential equations. In this study, the 3-step sequential model developed by Simpson (J Pharmacol Exp Ther 212:16-21,1980) was used to estimate upper limits of the times during which anti-toxins and other impermeable inhibitors of BoNT/A can exert an effect. The experimentally determined binding reaction rate was verified to be consistent with published estimates for the rate constants for BoNT/A binding to and dissociating from its receptors. Because this 3-step model was not designed to reproduce temporal changes in paralysis with different toxin concentrations, a new BoNT/A species and rate (k(S)) were added at the beginning of the reaction sequence to create a 4-step scheme. This unbound initial species is transformed at a rate determined by k(S) to a free species that is capable of binding. By systematically adjusting the values of k(S), the 4-step model simulated the r…
units def: metaid_0000022
parameter: metaid_0000003
units def: metaid_0000021
is part of: A05.1
rule: metaid_0000013
is described by: http://identifiers.org/pubmed/18551355
compartment: metaid_0000006
reaction: metaid_0000017
reaction: metaid_0000015
creator:
  ORG:
    orgname: EMBL-EBI
  n:
    given: Lukas
    family: Endler
substance units: metaid_0000019
species: metaid_0000012
species: metaid_0000004
compartment: metaid_0000007
compartment: metaid_0000005
time units: metaid_0000021
species: metaid_0000009
created:
  W3 CDTF: Fri Aug 08 16:57:53 BST 2008
is version of: REACT 11184.1
is derived from: http://identifiers.org/pubmed/6243359
reaction: metaid_0000018
occurs in: http://identifiers.org/taxonomy/9606
area units: metaid_0000005
reaction: metaid_0000016
modified:
  W3 CDTF: Wed May 16 11:02:56 BST 2012
species: metaid_0000010
species: metaid_0000011
volume units: metaid_0000020
is: MODEL8472829123
occurs in: http://identifiers.org/taxonomy/10090
units def: metaid_0000019
units def: metaid_0000020
species: metaid_0000008

metaid_0000010
has part: C07946
constant: false
boundary condition: false
has only substance units: false
initial concentration: 0.0
initial amount: NaN
in compartment: metaid_0000005
name: bound_BoNT/A
type: Species

metaid_0000021
unit: 930233
name: min
type: SBMLUnitsDef

930380
stoichiometry: 1.0
species: metaid_0000009
type: SpeciesReference

metaid_0000018
kinetic law: 930392
product: 930380
reactant: 930368
is version of: GO:0006858
fast: false
reversible: false
type: Reaction

metaid_0000008
is: C07946
constant: false
boundary condition: false
has only substance units: false
initial concentration: 1.0
initial amount: NaN
in compartment: metaid_0000005
name: bulk_BoNT/A
type: Species

990538
units: metaid_0000022
value: 0.013
type: LocalParameter

990540
units: metaid_0000022
value: 1.5E-4
type: LocalParameter

930269
stoichiometry: 1.0
species: metaid_0000011
type: SpeciesReference

930294
stoichiometry: 1.0
species: metaid_0000011
type: SpeciesReference

930233
exponent: 1.0
scale: 0
multipler: 60.0
kind: SECOND
type: SBMLUnit

metaid_0000003
constant: false
value: NaN
type: Parameter

metaid_0000017
kinetic law: 930356
product: 930344
reactant: 930331
is version of: REACT 11084.1
fast: false
reversible: false
type: Reaction

metaid_0000022
unit: 930245
name: perminute
type: SBMLUnitsDef

metaid_0000007
is version of: GO:0043679
is version of: GO:0005829
constant: true
size: 1.0
spatial dimensions: 3.0
name: neuroplasm
type: Compartment

990539
units: metaid_0000022
value: 0.058
type: LocalParameter