Open AccessMathematical modelling of metabolic pathways affected by an enzyme deficiency
Author(s) -
SCHUSTER Ronny,
JACOBASCH Gisela,
HOLZHÜTTER HermannGeorg
Publication year - 1989
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1989.tb14869.x
Subject(s) - pentose phosphate pathway , dehydrogenase , glycolysis , oxidative phosphorylation , methylene blue , metabolic pathway , biochemistry , enzyme , glucose 6 phosphate dehydrogenase , chemistry , glutathione , metabolism , flux (metallurgy) , biology , photocatalysis , catalysis , organic chemistry
The effects of various forms of glucose‐6‐phosphate dehydrogenase deficiency on erythrocyte metabolism have been studied on the basis of a complex mathematical model which comprises the main pathways of this cell: glycolysis, pentose pathway, reactions of the glutathione and adenine nucleotide metabolism. The calculated flux rates through the oxidative pentose pathway with and without methylene blue are in good accord with experimental results. The degree of deficiency as predicted by the model on the basis of calculated upper oxidative load boundaries, as well as of maximal methylene blue stimulation, correlates with the individual clinical manifestation of the metabolic disease. Therefore, the model allows one to judge the degree of metabolic disorder in the presence of glucose‐6‐phosphate dehydrogenase enzymopathies if the kinetic properties of the defect enzyme are known. Experimentally accessible parameters for an assessment of the oxidative load capacity of cells in vivo are proposed. It is pointed out that the threshold of tolerance as to energetic load is drastically reduced in the case of severe glucose‐6‐phosphate dehydrogenase deficiency.