public model
Model Identifier
BIOMD0000000106
Short description

This model is according to the paper Dynamic Simulation on the Arachidonic Acid Metabolic Network . Figure 2A has been reproduced by SBML ode solver on line. In the original model, all the reactions are presented as ODE directly. So curator rewrite each reaction according to the semantics of the paper. In this paper, the authors used quict complex kinetics law to describe the catalysis in the network, curators did not necessarily know all the complete meanings of the paper.


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.

In summary, you are entitled to use this encoded model in absolutely any manner you deem suitable, verbatim, or with modification, alone or embedded it in a larger context, redistribute it, commercially or not, in a restricted way or not.


To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92.

Format
SBML (L2V1)
Related Publication
  • Dynamic simulations on the arachidonic acid metabolic network.
  • Yang K, Ma W, Liang H, Ouyang Q, Tang C, Lai L
  • PLoS computational biology , 3/ 2007 , Volume 3 , pages: e55 , PubMed ID: 17381237
  • Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.
  • Drug molecules not only interact with specific targets, but also alter the state and function of the associated biological network. How to design drugs and evaluate their functions at the systems level becomes a key issue in highly efficient and low-side-effect drug design. The arachidonic acid metabolic network is the network that produces inflammatory mediators, in which several enzymes, including cyclooxygenase-2 (COX-2), have been used as targets for anti-inflammatory drugs. However, neither the century-old nonsteriodal anti-inflammatory drugs nor the recently revocatory Vioxx have provided completely successful anti-inflammatory treatment. To gain more insights into the anti-inflammatory drug design, the authors have studied the dynamic properties of arachidonic acid (AA) metabolic network in human polymorphous leukocytes. Metabolic flux, exogenous AA effects, and drug efficacy have been analyzed using ordinary differential equations. The flux balance in the AA network was found to be important for efficient and safe drug design. When only the 5-lipoxygenase (5-LOX) inhibitor was used, the flux of the COX-2 pathway was increased significantly, showing that a single functional inhibitor cannot effectively control the production of inflammatory mediators. When both COX-2 and 5-LOX were blocked, the production of inflammatory mediators could be completely shut off. The authors have also investigated the differences between a dual-functional COX-2 and 5-LOX inhibitor and a mixture of these two types of inhibitors. Their work provides an example for the integration of systems biology and drug discovery.
Contributors
Kun Yang

Metadata information

is
BioModels Database MODEL8610058649
BioModels Database BIOMD0000000106
isDescribedBy
PubMed 17381237
hasTaxon
Taxonomy Homo sapiens
isVersionOf
isPartOf

Curation status
Curated

Tags
Name Description Size Actions

Model files

BIOMD0000000106_url.xml SBML L2V1 representation of Yang2007_ArachidonicAcid 72.26 KB Preview | Download

Additional files

BIOMD0000000106-biopax2.owl Auto-generated BioPAX (Level 2) 48.78 KB Preview | Download
BIOMD0000000106.sci Auto-generated Scilab file 8.85 KB Preview | Download
BIOMD0000000106-biopax3.owl Auto-generated BioPAX (Level 3) 68.13 KB Preview | Download
BIOMD0000000106.m Auto-generated Octave file 13.55 KB Preview | Download
BIOMD0000000106.xpp Auto-generated XPP file 9.69 KB Preview | Download
BIOMD0000000106.pdf Auto-generated PDF file 270.69 KB Preview | Download
BIOMD0000000106.png Auto-generated Reaction graph (PNG) 445.32 KB Preview | Download
BIOMD0000000106_urn.xml Auto-generated SBML file with URNs 76.51 KB Preview | Download
BIOMD0000000106.vcml Auto-generated VCML file 83.67 KB Preview | Download
BIOMD0000000106.svg Auto-generated Reaction graph (SVG) 80.45 KB Preview | Download

  • Model originally submitted by : Kun Yang
  • Submitted: 09-Apr-2007 20:28:33
  • Last Modified: 10-Oct-2014 12:07:42
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 10-Oct-2014 12:07:42
    • Submitted by: Kun Yang
    • With comment: Current version of Yang2007_ArachidonicAcid
  • Version: 1 public model Download this version
    • Submitted on: 09-Apr-2007 20:28:33
    • Submitted by: Kun Yang
    • With comment: Original import of AAnetwork
Legends
: Variable used inside SBML models


Species
Species Initial Concentration/Amount
TXA2

thromboxane A2 ; Thromboxane A2
0.001 μmol
TXB2

thromboxane B2 ; Thromboxane B2
0.001 μmol
AA

arachidonic acid ; Arachidonate
0.001 μmol
5-HPETE

5(S)-HPETE ; 5(S)-HPETE
0.001 μmol
5-HETE

5(S)-HETE ; 5(S)-HETE
0.001 μmol
LTA4

leukotriene A4
0.001 μmol
LTB4

leukotriene B4
0.001 μmol
w-LTB4

20-hydroxy-leukotriene B4
0.001 μmol
15-LOX

Arachidonate 15-lipoxygenase
1.5 μmol
12-LOX

Arachidonate 12-lipoxygenase, 12S-type
0.5 μmol
5-LOX

Arachidonate 5-lipoxygenase
5.0 μmol
LTA4H

Leukotriene A-4 hydrolase
0.76 μmol
Reactions
Reactions Rate Parameters
(TXA2) => ()

([thromboxane A2; Thromboxane A2]) => ()
cell*kd8*x8

cell*kd8*[thromboxane A2; Thromboxane A2]
kd8 = 0.1
() => (TXB2)

() => ([thromboxane B2; Thromboxane B2])
kd8*x8*cell

kd8*[thromboxane A2; Thromboxane A2]*cell
kd8 = 0.1
() => (AA)

() => ([arachidonic acid; Arachidonate])
cell*K15*x15*lin*(1+x4/KI19+x2/KI20+x13/KI21+x11/KI22)/(lin+k15*(1+x1/ks))

cell*K15*[Phospholipase A2]*lin*(1+[12(S)-HPETE; 12(S)-HPETE]/KI19+[15(S)-HPETE; 15(S)-HPETE]/KI20+[leukotriene B4]/KI21+[5(S)-HETE; 5(S)-HETE]/KI22)/(lin+k15*(1+[arachidonic acid; Arachidonate]/ks))
K15 = 3600.0; KI21 = 500.0; lin = 12.0; ks = 500.0; k15 = 2600.0; KI22 = 500.0; KI19 = 500.0; KI20 = 200.0
(AA) => (12-HPETE)

([arachidonic acid; Arachidonate]) => ([12(S)-HPETE; 12(S)-HPETE])
cell*K17*x17*x1/(x1+k17*(1+x4/ki18+x3/ki16+x4/ks))

cell*K17*[Arachidonate 12-lipoxygenase, 12S-type]*[arachidonic acid; Arachidonate]/([arachidonic acid; Arachidonate]+k17*(1+[12(S)-HPETE; 12(S)-HPETE]/ki18+[15(S)-HETE; (15S)-15-Hydroxy-5,8,11-cis-13-trans-eicosatetraenoate]/ki16+[12(S)-HPETE; 12(S)-HPETE]/ks))
ks = 500.0; ki18 = 10.0; ki16 = 10.0; k17 = 50.0; K17 = 1000.0
(AA) => (5-HPETE)

([arachidonic acid; Arachidonate]) => ([5(S)-HPETE; 5(S)-HPETE])
cell*K21*x21*x1/(x1+k21*(1+x5/ki7+x3/ki8+x7/ki11+x11/ki12+x10/ks))

cell*K21*[Arachidonate 5-lipoxygenase]*[arachidonic acid; Arachidonate]/([arachidonic acid; Arachidonate]+k21*(1+[12(S)-HETE; 12(S)-HETE]/ki7+[15(S)-HETE; (15S)-15-Hydroxy-5,8,11-cis-13-trans-eicosatetraenoate]/ki8+[prostaglandin E2; Prostaglandin E2]/ki11+[5(S)-HETE; 5(S)-HETE]/ki12+[5(S)-HPETE; 5(S)-HPETE]/ks))
k21 = 5.0; ks = 500.0; ki8 = 4.0; ki7 = 30.0; ki11 = 15.0; K21 = 5000.0; ki12 = 6.3
(5-HPETE) => (LTA4)

([5(S)-HPETE; 5(S)-HPETE]) => ([leukotriene A4])
cell*K21*x21*x10/(x10+k21*(1+x5/ki7+x3/ki8+x7/ki11+x11/ki12+x12/ks))

cell*K21*[Arachidonate 5-lipoxygenase]*[5(S)-HPETE; 5(S)-HPETE]/([5(S)-HPETE; 5(S)-HPETE]+k21*(1+[12(S)-HETE; 12(S)-HETE]/ki7+[15(S)-HETE; (15S)-15-Hydroxy-5,8,11-cis-13-trans-eicosatetraenoate]/ki8+[prostaglandin E2; Prostaglandin E2]/ki11+[5(S)-HETE; 5(S)-HETE]/ki12+[leukotriene A4]/ks))
k21 = 5.0; ks = 500.0; ki8 = 4.0; ki7 = 30.0; ki11 = 15.0; K21 = 5000.0; ki12 = 6.3
(5-HETE) => ()

([5(S)-HETE; 5(S)-HETE]) => ()
kd11*x11*cell

kd11*[5(S)-HETE; 5(S)-HETE]*cell
kd11 = 0.001
(LTA4) => (LTB4)

([leukotriene A4]) => ([leukotriene B4])
cell*K22*x22*x12/(x12+k22*(1+x13/ks))

cell*K22*[Leukotriene A-4 hydrolase]*[leukotriene A4]/([leukotriene A4]+k22*(1+[leukotriene B4]/ks))
K22 = 125.0; ks = 500.0; k22 = 20.0
(LTB4) => (w-LTB4)

([leukotriene B4]) => ([20-hydroxy-leukotriene B4])
cell*K23*x23*x13/(x13+k23*(1+x5/ki14+x11/ki15+x14/ks))

cell*K23*[Docosahexaenoic acid omega-hydroxylase CYP4F3]*[leukotriene B4]/([leukotriene B4]+k23*(1+[12(S)-HETE; 12(S)-HETE]/ki14+[5(S)-HETE; 5(S)-HETE]/ki15+[20-hydroxy-leukotriene B4]/ks))
ks = 500.0; K23 = 150.0; ki14 = 0.2; ki15 = 0.86; k23 = 3.9
(15-LOX) => ()

([Arachidonate 15-lipoxygenase]) => ()
cell*kd16*x16

cell*kd16*[Arachidonate 15-lipoxygenase]
kd16 = 0.01
(12-LOX) => ()

([Arachidonate 12-lipoxygenase, 12S-type]) => ()
cell*ki17*x2*x17

cell*ki17*[15(S)-HPETE; 15(S)-HPETE]*[Arachidonate 12-lipoxygenase, 12S-type]
ki17 = 10.0
() => (5-LOX)

() => ([Arachidonate 5-lipoxygenase])
cell*KI23*x13*x21

cell*KI23*[leukotriene B4]*[Arachidonate 5-lipoxygenase]
KI23 = 0.053
(LTA4H) => ()

([Leukotriene A-4 hydrolase]) => ()
cell*K22*x22*x12/((x12+k22)*129)

cell*K22*[Leukotriene A-4 hydrolase]*[leukotriene A4]/(([leukotriene A4]+k22)*129)
K22 = 125.0; k22 = 20.0
Curator's comment:
(added: 23 Mar 2007, 20:57:51, updated: 23 Mar 2007, 20:57:51)
Figure 2A has been reproduced by SBML ode solver on line.