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BIOMD0000000143 - Olsen2003_neutrophil_oscillatory_metabolism

 

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Reference Publication
Publication ID: 12524266
Olsen LF, Kummer U, Kindzelskii AL, Petty HR.
A model of the oscillatory metabolism of activated neutrophils.
Biophys. J. 2003 Jan; 84(1): 69-81
European Media Laboratory, Schloss-Wolfsbrunnenweg 33, D-69118 Heidelberg, Germany. lfo@dou.dk  [more]
Model
Original Model: BIOMD0000000143.origin
Submitter: Harish Dharuri
Submission ID: MODEL5564211615
Submission Date: 15 Aug 2007 21:55:54 UTC
Last Modification Date: 03 Jun 2014 13:27:26 UTC
Creation Date: 27 Jul 2007 08:45:32 UTC
Encoders:  Harish Dharuri
set #1
bqmodel:isDerivedFrom PubMed 11901676
DOI 10.1021/j100023a001
set #2
bqbiol:isVersionOf Gene Ontology NADH peroxidase activity
Gene Ontology melatonin metabolic process
bqbiol:hasTaxon Taxonomy Mammalia
Notes
Olsen2003_neutrophil_oscillatory_metabolism

This model is described in the article:

Olsen LF, Kummer U, Kindzelskii AL, Petty HR.
Biophys. J. 2003 Jan; 84(1): 69-81

Abstract:

We present a two-compartment model to explain the oscillatory behavior observed experimentally in activated neutrophils. Our model is based mainly on the peroxidase-oxidase reaction catalyzed by myeloperoxidase with melatonin as a cofactor and NADPH oxidase, a major protein in the phagosome membrane of the leukocyte. The model predicts that after activation of a neutrophil, an increase in the activity of the hexose monophosphate shunt and the delivery of myeloperoxidase into the phagosome results in oscillations in oxygen and NAD(P)H concentration. The period of oscillation changes from >200 s to 10-30 s. The model is consistent with previously reported oscillations in cell metabolism and oxidant production. Key features and predictions of the model were confirmed experimentally. The requirement of the hexose monophosphate pathway for 10 s oscillations was verified using 6-aminonicotinamide and dexamethasone, which are inhibitors of glucose-6-phosphate dehydrogenase. The role of the NADPH oxidase in promoting oscillations was confirmed by dose-response studies of the effect of diphenylene iodonium, an inhibitor of the NADPH oxidase. Moreover, the model predicted an increase in the amplitude of NADPH oscillations in the presence of melatonin, which was confirmed experimentally. Successful computer modeling of complex chemical dynamics within cells and their chemical perturbation will enhance our ability to identify new antiinflammatory compounds.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Model
Publication ID: 12524266 Submission Date: 15 Aug 2007 21:55:54 UTC Last Modification Date: 03 Jun 2014 13:27:26 UTC Creation Date: 27 Jul 2007 08:45:32 UTC
Mathematical expressions
Reactions
Myeloperoxidase reaction Melatonin-compound I reaction Melatonin-compound II reaction compound III formation
H2O2 formation compound III-superoxide reaction NADPH autooxidation NADP radical-Oxygen reaction
H2O2 formation NADP free radical formation NADP dimer formation NADPH synthesis
Oxygen diffusion Oxygen diffusion Oxygen diffusion- phagosome/cytoplasm H2O2 diffusion phagosome/cytoplasm
Melatonin diffusion phagosome/cytoplasm Melatonin free radical diffusion phagosome/cytoplasm Superoxide diffusion phagosome/cytoplasm NADPH oxidase activity
Physical entities
Compartments Species
phagosome H2O2 Ferric peroxidase compound I
Melatonin compound II Melatonin free radical
Superoxide Hydrogen Oxygen
compound III    
cytoplasm NADPH Oxygen NADP
H2O2 NADP Superoxide
Hydrogen Melatonin free radical Melatonin
NADP2    
Global parameters
Knadph k1 kminus1 k2
k3 k4 k5 k6
k7 k8 k9 k10
k11 k12 k13 kminus13
k14 k15 k16 k17
k18 V L Ko
Reactions (20)
 
 Myeloperoxidase reaction [Ferric peroxidase] + [H2O2] → [compound I];  
 
 Melatonin-compound I reaction [Melatonin] + [compound I] → [Melatonin free radical] + [compound II];  
 
 Melatonin-compound II reaction [Melatonin] + [compound II] → [Melatonin free radical] + [Ferric peroxidase];  
 
 compound III formation [Superoxide] + [Ferric peroxidase] → [compound III];  
 
 H2O2 formation 2.0 × [Superoxide] + 2.0 × [Hydrogen] → [Oxygen] + [H2O2];  
 
 compound III-superoxide reaction [Superoxide] + [compound III] → [Oxygen] + [compound I];  
 
 NADPH autooxidation [Oxygen] + [NADPH] → [H2O2] + [NADP];  
 
 NADP radical-Oxygen reaction [Oxygen] + [NADP] → [Superoxide] + [NADP];  
 
 H2O2 formation 2.0 × [Superoxide] + 2.0 × [Hydrogen] → [Oxygen] + [H2O2];  
 
 NADP free radical formation [NADPH] + [Melatonin free radical] → [NADP] + [Melatonin];  
 
 NADP dimer formation 2.0 × [NADP] → [NADP2];  
 
 NADPH synthesis  → [NADPH];  
 
 Oxygen diffusion  → [Oxygen];  
 
 Oxygen diffusion [Oxygen] → ;  
 
 Oxygen diffusion- phagosome/cytoplasm [Oxygen] → [Oxygen];  
 
 H2O2 diffusion phagosome/cytoplasm [H2O2] → [H2O2];  
 
 Melatonin diffusion phagosome/cytoplasm [Melatonin] → [Melatonin];  
 
 Melatonin free radical diffusion phagosome/cytoplasm [Melatonin free radical] → [Melatonin free radical];  
 
 Superoxide diffusion phagosome/cytoplasm [Superoxide] → [Superoxide];  
 
 NADPH oxidase activity 2.0 × [Oxygen] + [NADPH] → 2.0 × [Superoxide] + [NADP];  
 
 phagosome Spatial dimensions: 3.0  Compartment size: 1.0
 
 H2O2
Compartment: phagosome
Initial concentration: 0.0
 
 Ferric peroxidase
Compartment: phagosome
Initial concentration: 300.0
 
 compound I
Compartment: phagosome
Initial concentration: 0.0
 
 Melatonin
Compartment: phagosome
Initial concentration: 300.0
 
 compound II
Compartment: phagosome
Initial concentration: 0.0
 
 Melatonin free radical
Compartment: phagosome
Initial concentration: 0.0
 
 Superoxide
Compartment: phagosome
Initial concentration: 0.0
 
 Hydrogen
Compartment: phagosome
Initial concentration: 0.0
 
 Oxygen
Compartment: phagosome
Initial concentration: 0.0
 
 compound III
Compartment: phagosome
Initial concentration: 0.0
 
 cytoplasm Spatial dimensions: 3.0  Compartment size: 10.0
 
 NADPH
Compartment: cytoplasm
Initial concentration: 0.0
 
 Oxygen
Compartment: cytoplasm
Initial concentration: 0.0
 
 NADP
Compartment: cytoplasm
Initial concentration: 0.0
 
 H2O2
Compartment: cytoplasm
Initial concentration: 0.0
 
 NADP
Compartment: cytoplasm
Initial concentration: 0.0
 
 Superoxide
Compartment: cytoplasm
Initial concentration: 0.0
 
 Hydrogen
Compartment: cytoplasm
Initial concentration: 0.0
 
 Melatonin free radical
Compartment: cytoplasm
Initial concentration: 0.0
 
 Melatonin
Compartment: cytoplasm
Initial concentration: 300.0
 
 NADP2
Compartment: cytoplasm
Initial concentration: 0.0
 
Global Parameters (24)
 
   Knadph
Value: 60.0
Constant
 
   k1
Value: 50.0
Constant
 
   kminus1
Value: 58.0
Constant
 
   k2
Value: 10.0
Constant
 
   k3
Value: 0.0040
Constant
 
   k4
Value: 20.0
Constant
 
   k5
Value: 10.0
Constant
 
   k6
Value: 0.1
Constant
 
   k7
Value: 1.0E-6
Constant
 
   k8
Value: 50.0
Constant
 
   k9
Value: 500.0
Constant
 
   k10
Value: 10.0
Constant
 
   k11
Value: 60.0
Constant
 
   k12
Value: 25.0
Constant
 
   k13
Value: 12.5
Constant
 
   kminus13
Value: 0.045
Constant
 
   k14
Value: 30.0
Constant
 
   k15
Value: 30.0
Constant
 
   k16
Value: 10.0
Constant
 
   k17
Value: 10.0
Constant
 
   k18
Value: 2.0
Constant
 
   V
Value: 288.0
Constant
 
   L
Value: 550.0
Constant
 
   Ko
Value: 1.5
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000143

Curator's comment: (updated: 27 Jul 2007 20:44:35 BST)

The plot reproduces Fig 2 of the paper. Simulation result obtained from MathSBML.

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