public model
Short description

The model should reproduce the figure 2F of the article.

The equation 7 has been split into equations 7a-7c, in order to take into account the different flux rates of Lysine and CML formation from Schiff.

The model was tested in Jarnac (SBML L2 V1) and Copasi (SBML L2 V3).

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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.

Related Publication
  • A quantitative model of the generation of N(epsilon)-(carboxymethyl)lysine in the Maillard reaction between collagen and glucose.
  • Ferreira AE, Ponces Freire AM, Voit EO
  • The Biochemical journal , 11/ 2003 , Volume 376 , pages: 109-121
  • Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade de Lisboa, Bloco C8, Campo Grande, 1749-016 Lisboa, Portugal. aeferreira@fc.ul.pt
  • The Maillard reaction between reducing sugars and amino groups of biomolecules generates complex structures known as AGEs (advanced glycation endproducts). These have been linked to protein modifications found during aging, diabetes and various amyloidoses. To investigate the contribution of alternative routes to the formation of AGEs, we developed a mathematical model that describes the generation of CML [ N(epsilon)-(carboxymethyl)lysine] in the Maillard reaction between glucose and collagen. Parameter values were obtained by fitting published data from kinetic experiments of Amadori compound decomposition and glycoxidation of collagen by glucose. These raw parameter values were subsequently fine-tuned with adjustment factors that were deduced from dynamic experiments taking into account the glucose and phosphate buffer concentrations. The fine-tuned model was used to assess the relative contributions of the reaction between glyoxal and lysine, the Namiki pathway, and Amadori compound degradation to the generation of CML. The model suggests that the glyoxal route dominates, except at low phosphate and high glucose concentrations. The contribution of Amadori oxidation is generally the least significant at low glucose concentrations. Simulations of the inhibition of CML generation by aminoguanidine show that this compound effectively blocks the glyoxal route at low glucose concentrations (5 mM). Model results are compared with literature estimates of the contributions to CML generation by the three pathways. The significance of the dominance of the glyoxal route is discussed in the context of possible natural defensive mechanisms and pharmacological interventions with the goal of inhibiting the Maillard reaction in vivo.
Harish Dharuri

Metadata information

BioModels Database MODEL0733584307
BioModels Database BIOMD0000000053
PubMed 12911334
Taxonomy Homo sapiens
Gene Ontology collagen binding
Gene Ontology peptidyl-lysine modification
Human Disease Ontology diabetes mellitus
Human Disease Ontology amyloidosis
Curation status
  • Model originally submitted by : Harish Dharuri
  • Submitted: 09-Apr-2006 22:05:31
  • Last Modified: 09-Oct-2014 16:39:20
  • Version: 2 public model Download this version
    • Submitted on: 09-Oct-2014 16:39:20
    • Submitted by: Harish Dharuri
    • With comment: Current version of Ferreira2003_CML_generation2
  • Version: 1 public model Download this version
    • Submitted on: 09-Apr-2006 22:05:31
    • Submitted by: Harish Dharuri
    • With comment: Original import of BIOMD0000000053.xml.origin
Curator's comment:
(added: 27 Aug 2009, 16:50:45, updated: 27 Aug 2009, 16:50:45)
The model reproduces the time profiles of Amadori and CML for oxidative conditions as shown in Fig 2 F. Please note that the variables are expressed as a fraction of total lysine. Simulation result obtained with Copasi 4.5 (build 30).