Metabolic pathway analysis of enzyme-deficient human red blood cells

被引:28
作者
Çakir, T [1 ]
Tacer, CS [1 ]
Ülgen, KO [1 ]
机构
[1] Bogazici Univ, Dept Chem Engn, TR-34342 Istanbul, Turkey
关键词
stoichiometric modeling; elementary flux modes; control-effective flux; erythrocyte enzymopathy; metabolic pathway analysis;
D O I
10.1016/j.biosystems.2004.06.004
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Five enzymopathies (G6PDH, TPI, PGI, DPGM and PGK deficiencies) in the human red blood cells are investigated using a stoichiometric modeling approach, i.e., metabolic pathway analysis. Elementary flux modes (EFMs) corresponding to each enzyme deficiency case are analyzed in terms of functional capabilities. When available, experimental findings reported in literature related to metabolic behavior of the human red blood cells are compared with the results of EFM analysis. Control-effective flux (CEF) calculation, a novel approach which allows quantification and interpretation of determined EFMs, is performed for further analysis of enzymopathies. Glutathione reductase reaction is found to be the most effective reaction in terms of its CEF value in all enzymopathies in parallel with its known essential role for red blood cells. Efficiency profiles of the enzymatic reactions upon the degree of enzyme deficiency are obtained by the help of the CEF approach, as a basis for future experimental studies. CEF analysis, which is found to be promising in the analysis of erythrocyte enzymopathies, has the potential to be used in modeling efforts of human metabolism. (C) 2004 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:49 / 67
页数:19
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