Difference between revisions of "N-Glycan biosynthesis"
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[[File:N-Glycan1.JPG|thumb|The first version of the model, made in the system BioUML]] | [[File:N-Glycan1.JPG|thumb|The first version of the model, made in the system BioUML]] | ||
| − | [[File:KOR 238.JPG|thumb|Model and experiment | + | [[File:KOR 238.JPG|thumb|Model and experiment glycan peaks GP1-GP24 concentrations for the patient KOR_238]] |
[[File:Compartment1.jpg|thumb|Model of the first Golgi compartment]] | [[File:Compartment1.jpg|thumb|Model of the first Golgi compartment]] | ||
Revision as of 15:39, 1 April 2014
Contents |
Introduction
N-Linked glycans are attached in the endoplasmic reticulum to the nitrogen (N) in the side chain of asparagine in the sequon. The sequon is an Asn-X-Ser or Asn-X-Thr sequence, where X is any amino acid except proline and the glycan may be composed of N-acetyl galactosamine, galactose, neuraminic acid, N-acetylglucosamine, fructose, mannose, fucose, and other monosaccharides.
N-linked glycans are extremely important in proper protein folding in eukaryotic cells, in cell-cell interactions and in personalized medicine[1].
Mathematical model of N-Glycan biosynthesis
Model realization
Because of an important role of N-Glycans in personalized medicine it was decided to work out a mathematical model of its biosynthesis in BioUML. The research was begun with Reference pathway from KEGG database implementation [2].
Reaction rate equations were generated by KEGGtranslator[3], a number of necessary parameters, such as Michaelis-Menten constants, were taken from BRENDA Enzyme Database[4].
Model optimization
The next step was the model reduction: the decrease in the number of model parameters and materials, which allowed to significantly simplify the model, speed up the Simulation and compare the model results with the experiment.
We use the expiremental data for Korcula population [5] and made the Optimization of model parameters was performed for every individual patient.
To give more intuitive representation Glycan structures property was used and to achieve the optimum accuracy we supposed that the distribution of the N-glycans in each Golgi compartment is modeled as a well-mixed reactor[6].
References
- ↑ en.wikipedia.org/wiki/Glycan
- ↑ N-Glycan biosynthesis - Reference pathway
- ↑ KEGGtranslator
- ↑ BRENDA
- ↑ High throughput isolation and glycosylation analysis of IgG-variability and heritability of the IgG glycome in three isolated human populations.
- ↑ Systems Analysis of N-Glycan Processing in Mammalian Cells
