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BIOMD0000000015 - Curto1998 - purine metabolism

 

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Reference Publication
Publication ID: 9664759
Curto R, Voit EO, Sorribas A, Cascante M.
Mathematical models of purine metabolism in man.
Math Biosci 1998 Jul; 151(1): 1-49
Departament de Bioquímica i Biología Molecular, Facultat de Químiques, Universitat de Barcelona, Catalunya, Spain.  [more]
Model
Original Model: BIOMD0000000015.origin
Submitter: Nicolas Le Novère
Submission ID: MODEL6617035399
Submission Date: 13 Sep 2005 13:11:12 UTC
Last Modification Date: 02 Jul 2014 16:48:59 UTC
Creation Date: 06 Mar 2005 13:52:00 UTC
Encoders:  Nicolas Le Novère
   Tomas Radivoyevitch
set #1
bqbiol:isVersionOf Gene Ontology purine nucleobase metabolic process
set #2
bqbiol:is KEGG Pathway Purine metabolism - Homo sapiens (human)
Reactome REACT_522
set #3
bqbiol:hasTaxon Taxonomy Homo sapiens
Notes
Curto1998 - purine metabolism

This is a purine metabolism model that is geared toward studies of gout.

The model uses Generalized Mass Action (GMA; i.e. power law) descriptions of reaction rate laws.

Such descriptions are local approximations that assume independent substrate binding.

This model is described in the article:

Curto R, Voit EO, Sorribas A, Cascante M.
Math Biosci 1998 Jul; 151(1): 1-49

Abstract:

Experimental and clinical data on purine metabolism are collated and analyzed with three mathematical models. The first model is the result of an attempt to construct a traditional kinetic model based on Michaelis-Menten rate laws. This attempt is only partially successful, since kinetic information, while extensive, is not complete, and since qualitative information is difficult to incorporate into this type of model. The data gaps necessitate the complementation of the Michaelis-Menten model with other functional forms that can incorporate different types of data. The most convenient and established representations for this purpose are rate laws formulated as power-law functions, and these are used to construct a Complemented Michaelis-Menten (CMM) model. The other two models are pure power-law-representations, one in the form of a Generalized Mass Action (GMA) system, and the other one in the form of an S-system. The first part of the paper contains a compendium of experimental data necessary for any model of purine metabolism. This is followed by the formulation of the three models and a comparative analysis. For physiological and moderately pathological perturbations in metabolites or enzymes, the results of the three models are very similar and consistent with clinical findings. This is an encouraging result since the three models have different structures and data requirements and are based on different mathematical assumptions. Significant enzyme deficiencies are not so well modeled by the S-system model. The CMM model captures the dynamics better, but judging by comparisons with clinical observations, the best model in this case is the GMA model. The model results are discussed in some detail, along with advantages and disadvantages of each modeling strategy.

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: 9664759 Submission Date: 13 Sep 2005 13:11:12 UTC Last Modification Date: 02 Jul 2014 16:48:59 UTC Creation Date: 06 Mar 2005 13:52:00 UTC
Mathematical expressions
Reactions
ada ade adna adrnr
ampd aprt arna asuc
asli dada den dgnuc
dnaa dnag gdna gdrnr
gmpr gmps gnuc gprt
grna gua hprt hx
hxd impd inuc mat
polyam prpps pyr rnaa
rnag trans ua x
xd      
Physical entities
Compartments Species
cell phosphoribosylpyrophosphate inosine monophosphate adenylosuccinate
ATP_ADP_AMP_Ado s-adenosyl-L-methionine adenine
xanthosine monophosphate GTP_GDP_GMP dATP_dADP_dAMP_dAdo
dGTP_dGDP_dGMP RNA DNA
dIno_Ino_HX xanthine guanine
uric acid ribose-5-phosphate phosphate
Reactions (37)
 
 ada [ATP_ADP_AMP_Ado] → [dIno_Ino_HX];  
 
 ade [adenine] → ;  
 
 adna [dATP_dADP_dAMP_dAdo] → [DNA];   {dGTP_dGDP_dGMP}
 
 adrnr [ATP_ADP_AMP_Ado] → [dATP_dADP_dAMP_dAdo];   {dGTP_dGDP_dGMP} , {dATP_dADP_dAMP_dAdo}
 
 ampd [ATP_ADP_AMP_Ado] → [inosine monophosphate];   {GTP_GDP_GMP} , {phosphate}
 
 aprt [phosphoribosylpyrophosphate] + [adenine] → [ATP_ADP_AMP_Ado];   {ATP_ADP_AMP_Ado}
 
 arna [ATP_ADP_AMP_Ado] → [RNA];   {GTP_GDP_GMP}
 
 asuc [inosine monophosphate] → [adenylosuccinate];   {ATP_ADP_AMP_Ado} , {GTP_GDP_GMP} , {phosphate}
 
 asli [adenylosuccinate] → [ATP_ADP_AMP_Ado];   {ATP_ADP_AMP_Ado}
 
 dada [dATP_dADP_dAMP_dAdo] → [dIno_Ino_HX];  
 
 den [phosphoribosylpyrophosphate] → [inosine monophosphate];   {dGTP_dGDP_dGMP} , {inosine monophosphate} , {ATP_ADP_AMP_Ado} , {GTP_GDP_GMP} , {phosphate}
 
 dgnuc [dGTP_dGDP_dGMP] → [guanine];  
 
 dnaa [DNA] → [dATP_dADP_dAMP_dAdo];  
 
 dnag [DNA] → [dGTP_dGDP_dGMP];  
 
 gdna [dGTP_dGDP_dGMP] → [DNA];   {dATP_dADP_dAMP_dAdo}
 
 gdrnr [GTP_GDP_GMP] → [dGTP_dGDP_dGMP];   {dATP_dADP_dAMP_dAdo} , {dGTP_dGDP_dGMP}
 
 gmpr [GTP_GDP_GMP] → [inosine monophosphate];   {xanthosine monophosphate} , {ATP_ADP_AMP_Ado} , {inosine monophosphate}
 
 gmps [xanthosine monophosphate] → [GTP_GDP_GMP];   {ATP_ADP_AMP_Ado}
 
 gnuc [GTP_GDP_GMP] → [guanine];   {phosphate}
 
 gprt [guanine] + [phosphoribosylpyrophosphate] → [GTP_GDP_GMP];   {GTP_GDP_GMP}
 
 grna [GTP_GDP_GMP] → [RNA];   {ATP_ADP_AMP_Ado}
 
 gua [guanine] → [xanthine];  
 
 hprt [dIno_Ino_HX] + [phosphoribosylpyrophosphate] → [inosine monophosphate];   {inosine monophosphate}
 
 hx [dIno_Ino_HX] → ;  
 
 hxd [dIno_Ino_HX] → [xanthine];  
 
 impd [inosine monophosphate] → [xanthosine monophosphate];   {GTP_GDP_GMP} , {xanthosine monophosphate}
 
 inuc [inosine monophosphate] → [dIno_Ino_HX];   {phosphate}
 
 mat [ATP_ADP_AMP_Ado] → [s-adenosyl-L-methionine];   {s-adenosyl-L-methionine}
 
 polyam [s-adenosyl-L-methionine] → [adenine];  
 
 prpps [ribose-5-phosphate] → [phosphoribosylpyrophosphate];   {ATP_ADP_AMP_Ado} , {GTP_GDP_GMP} , {phosphate} , {phosphoribosylpyrophosphate}
 
 pyr [phosphoribosylpyrophosphate] → ;  
 
 rnaa [RNA] → [ATP_ADP_AMP_Ado];  
 
 rnag [RNA] → [GTP_GDP_GMP];  
 
 trans [s-adenosyl-L-methionine] → [ATP_ADP_AMP_Ado];  
 
 ua [uric acid] → ;  
 
 x [xanthine] → ;  
 
 xd [xanthine] → [uric acid];  
 
  Spatial dimensions: 3.0  Compartment size: 1.0
 
 phosphoribosylpyrophosphate
Compartment: cell
Initial amount: 5.01742
 
 inosine monophosphate
Compartment: cell
Initial amount: 98.2634
 
 adenylosuccinate
Compartment: cell
Initial amount: 0.198189
 
 ATP_ADP_AMP_Ado
Compartment: cell
Initial amount: 2475.35
 
 s-adenosyl-L-methionine
Compartment: cell
Initial amount: 3.99187
 
 adenine
Compartment: cell
Initial amount: 0.98473
 
 xanthosine monophosphate
Compartment: cell
Initial amount: 24.793
 
 GTP_GDP_GMP
Compartment: cell
Initial amount: 410.223
 
 dATP_dADP_dAMP_dAdo
Compartment: cell
Initial amount: 6.01413
 
 dGTP_dGDP_dGMP
Compartment: cell
Initial amount: 3.02581
 
 RNA
Compartment: cell
Initial amount: 28680.5
 
 DNA
Compartment: cell
Initial amount: 5179.34
 
 dIno_Ino_HX
Compartment: cell
Initial amount: 9.51785
 
 xanthine
Compartment: cell
Initial amount: 5.05941
 
 guanine
Compartment: cell
Initial amount: 5.50638
 
 uric acid
Compartment: cell
Initial amount: 100.293
 
 ribose-5-phosphate
Compartment: cell
Initial amount: 18.0
 
 phosphate
Compartment: cell
Initial amount: 1400.0
 
ada (2)
 
   aada
Value: 0.001062
Constant
 
   fada4
Value: 0.97
Constant
 
ade (2)
 
   aade
Value: 0.01
Constant
 
   fade6
Value: 0.55
Constant
 
adna (3)
 
   aadna
Value: 3.2789
Constant
 
   fdnap9
Value: 0.42
Constant
 
   fdnap10
Value: 0.33
Constant
 
adrnr (4)
 
   aadrnr
Value: 0.0602
Constant
 
   fadrnr4
Value: 0.1
Constant
 
   fadrnr9
Value: -0.3
Constant
 
   fadrnr10
Value: 0.87
Constant
 
ampd (4)
 
   aampd
Value: 0.02688
Constant
 
   fampd4
Value: 0.8
Constant
 
   fampd8
Value: -0.03
Constant
 
   fampd18
Value: -0.1
Constant
 
aprt (4)
 
   aaprt
Value: 233.8
Constant
 
   faprt1
Value: 0.5
Constant
 
   faprt4
Value: -0.8
Constant
 
   faprt6
Value: 0.75
Constant
 
arna (3)
 
   aarna
Value: 614.5
Constant
 
   frnap4
Value: 0.05
Constant
 
   frnap8
Value: 0.13
Constant
 
asuc (5)
 
   aasuc
Value: 3.5932
Constant
 
   fasuc2
Value: 0.4
Constant
 
   fasuc4
Value: -0.24
Constant
 
   fasuc8
Value: 0.2
Constant
 
   fasuc18
Value: -0.05
Constant
 
asli (3)
 
   aasli
Value: 66544.0
Constant
 
   fasli3
Value: 0.99
Constant
 
   fasli4
Value: -0.95
Constant
 
dada (2)
 
   adada
Value: 0.03333
Constant
 
   fdada9
Value: 1.0
Constant
 
den (6)
 
   aden
Value: 5.2728
Constant
 
   fden1
Value: 2.0
Constant
 
   fden2
Value: -0.06
Constant
 
   fden4
Value: -0.25
Constant
 
   fden8
Value: -0.2
Constant
 
   fden18
Value: -0.08
Constant
 
dgnuc (2)
 
   adgnuc
Value: 0.03333
Constant
 
   fdgnuc10
Value: 1.0
Constant
 
dnaa (2)
 
   adnaa
Value: 0.001938
Constant
 
   fdnan12
Value: 1.0
Constant
 
dnag (2)
 
   adnag
Value: 0.001318
Constant
 
   fdnan12
Value: 1.0
Constant
 
gdna (3)
 
   agdna
Value: 2.2296
Constant
 
   fdnap9
Value: 0.42
Constant
 
   fdnap10
Value: 0.33
Constant
 
gdrnr (4)
 
   agdrnr
Value: 0.1199
Constant
 
   fgdrnr8
Value: 0.4
Constant
 
   fgdrnr9
Value: -1.2
Constant
 
   fgdrnr10
Value: -0.39
Constant
 
gmpr (5)
 
   agmpr
Value: 0.3005
Constant
 
   fgmpr2
Value: -0.15
Constant
 
   fgmpr4
Value: -0.07
Constant
 
   fgmpr7
Value: -0.76
Constant
 
   fgmpr8
Value: 0.7
Constant
 
gmps (3)
 
   agmps
Value: 0.3738
Constant
 
   fgmps4
Value: 0.12
Constant
 
   fgmps7
Value: 0.16
Constant
 
gnuc (3)
 
   agnuc
Value: 0.2511
Constant
 
   fgnuc8
Value: 0.9
Constant
 
   fgnuc18
Value: -0.34
Constant
 
gprt (4)
 
   agprt
Value: 361.69
Constant
 
   fgprt1
Value: 1.2
Constant
 
   fgprt8
Value: -1.2
Constant
 
   fgprt15
Value: 0.42
Constant
 
grna (3)
 
   agrna
Value: 409.6
Constant
 
   frnap4
Value: 0.05
Constant
 
   frnap8
Value: 0.13
Constant
 
gua (2)
 
   agua
Value: 0.4919
Constant
 
   fgua15
Value: 0.5
Constant
 
hprt (4)
 
   ahprt
Value: 12.569
Constant
 
   fhprt1
Value: 1.1
Constant
 
   fhprt2
Value: -0.89
Constant
 
   fhprt13
Value: 0.48
Constant
 
hx (2)
 
   ahx
Value: 0.003793
Constant
 
   fhx13
Value: 1.12
Constant
 
hxd (2)
 
   ahxd
Value: 0.2754
Constant
 
   fhxd13
Value: 0.65
Constant
 
impd (4)
 
   aimpd
Value: 1.2823
Constant
 
   fimpd2
Value: 0.15
Constant
 
   fimpd7
Value: -0.09
Constant
 
   fimpd8
Value: -0.03
Constant
 
inuc (3)
 
   ainuc
Value: 0.9135
Constant
 
   finuc2
Value: 0.8
Constant
 
   finuc18
Value: -0.36
Constant
 
mat (3)
 
   amat
Value: 7.2067
Constant
 
   fmat4
Value: 0.2
Constant
 
   fmat5
Value: -0.6
Constant
 
polyam (2)
 
   apolyam
Value: 0.29
Constant
 
   fpolyam5
Value: 0.9
Constant
 
prpps (6)
 
   aprpps
Value: 0.9
Constant
 
   fprpps1
Value: -0.03
Constant
 
   fprpps4
Value: -0.45
Constant
 
   fprpps8
Value: -0.04
Constant
 
   fprpps17
Value: 0.65
Constant
 
   fprpps18
Value: 0.7
Constant
 
pyr (2)
 
   apyr
Value: 1.2951
Constant
 
   fpyr1
Value: 1.27
Constant
 
rnaa (2)
 
   arnaa
Value: 0.06923
Constant
 
   frnan11
Value: 1.0
Constant
 
rnag (2)
 
   arnag
Value: 0.04615
Constant
 
   frnan11
Value: 1.0
Constant
 
trans (2)
 
   atrans
Value: 8.8539
Constant
 
   ftrans5
Value: 0.33
Constant
 
ua (2)
 
   aua
Value: 8.744E-5
Constant
 
   fua16
Value: 2.21
Constant
 
x (2)
 
   ax
Value: 0.0012
Constant
 
   fx14
Value: 2.0
Constant
 
xd (2)
 
   axd
Value: 0.949
Constant
 
   fxd14
Value: 0.55
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000015

Curator's comment: (updated: 02 Jun 2008 14:14:13 BST)

Reproduction of figure 2b of the original publication, showing the time course of hypoxanthine of the GMA model in response to a PRPP pulse. As mentioned in the article, the concentration of PRPP was increased 10 fold from 5 to 50 microM. There seems to be a typo in the articles figure caption, as the increase of PRPP takes place at t =0 not 10.

The simulation was performed using Copasi 4.4 b.26.

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