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Pyrimidine nucleotide de novo biosynthesis as a model of metabolic control
Author(s) -
Rodriguez Mauricio Rodriguez,
Wales Melinda E.,
Good Theresa,
Wild James R
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a265
Subject(s) - pyrimidine metabolism , in silico , metabolic control analysis , metabolic pathway , biology , flux (metallurgy) , metabolic engineering , metabolic network , biosynthesis , computational biology , biochemistry , metabolism , chemistry , enzyme , microbiology and biotechnology , gene , purine , organic chemistry , insulin
This research presents a thorough investigation and description of metabolic control dynamics in vivo and in silico using as a model de novo pyrimidine biosynthesis in E. coli. The studies described provide a unique effort toward combining mathematical analysis with dynamic transition experimental data and emphasize the significance of providing a quantitative framework for understanding metabolic control. Biochemical flux through the pathway was analyzed under dynamic conditions using middle‐exponential growth and steady state cultures. Fluctuations of pathway intermediates and end products transitions were quantified in response to physiological perturbation. Rapid versus long‐term equilibrium shifts in metabolic adaptation was analyzed. Finally, monitoring enzymatic activity levels during metabolic transitions provided insight into the interaction of genetic and biochemical mechanisms of regulation. Thus, it was possible to construct a robust mathematical model that faithfully represented, with a remarkable predictability, the nature of the metabolic response to specific environmental perturbations. These studies constitute a significant contribution to quantitative biochemistry as well as in the field of metabolic control, which can be extended to other cellular processes as well as different organisms.