Reference : Predicting the impact of diet and enzymopathies on human small intestinal epithelial cells
Scientific journals : Article
Life sciences : Multidisciplinary, general & others
http://hdl.handle.net/10993/13031
Predicting the impact of diet and enzymopathies on human small intestinal epithelial cells
English
Sahoo, Swagatika [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > >]
Thiele, Ines mailto [University of Iceland > Faculty of Industrial Engineering, Mechanical Engineering & Computer Science]
2013
Human Molecular Genetics
22
13
2705-22
Yes (verified by ORBilu)
0964-6906
1460-2083
England
[en] Small intestinal epithelial cells (sIECs) have a significant share in whole body metabolism as they perform enzymatic digestion and absorption of nutrients. Furthermore, the diet plays a key role in a number of complex diseases including obesity and diabetes. The impact of diet and altered genetic backgrounds on human metabolism may be studied by using computational modeling. A metabolic reconstruction of human sIECs was manually assembled using the literature. The resulting sIEC model was subjected to two different diets to obtain condition-specific metabolic models. Fifty defined metabolic tasks evaluated the functionalities of these models, along with the respective secretion profiles, which distinguished between impacts of different dietary regimes. Under the average American diet, the sIEC model resulted in higher secretion flux for metabolites implicated in metabolic syndrome. In addition, enzymopathies were analyzed in the context of the sIEC metabolism. Computed results were compared with reported gastrointestinal (GI) pathologies and biochemical defects as well as with biomarker patterns used in their diagnosis. Based on our simulations, we propose that (i) sIEC metabolism is perturbed by numerous enzymopathies, which can be used to study cellular adaptive mechanisms specific for such disorders, and in the identification of novel co-morbidities, (ii) porphyrias are associated with both heme synthesis and degradation and (iii) disturbed intestinal gamma-aminobutyric acid synthesis may be linked to neurological manifestations of various enzymopathies. Taken together, the sIEC model represents a comprehensive, biochemically accurate platform for studying the function of sIEC and their role in whole body metabolism.
The Icelandic Research Fund (No. 100406022)
http://hdl.handle.net/10993/13031
10.1093/hmg/ddt119

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