کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4497809 1318951 2009 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The rational parameterisation theorem for multisite post-translational modification systems
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم کشاورزی و بیولوژیک علوم کشاورزی و بیولوژیک (عمومی)
پیش نمایش صفحه اول مقاله
The rational parameterisation theorem for multisite post-translational modification systems
چکیده انگلیسی

Post-translational modification of proteins plays a central role in cellular regulation but its study has been hampered by the exponential increase in substrate modification forms (“modforms”) with increasing numbers of sites. We consider here biochemical networks arising from post-translational modification under mass-action kinetics, allowing for multiple substrates, having different types of modification (phosphorylation, methylation, acetylation, etc.) on multiple sites, acted upon by multiple forward and reverse enzymes (in total number L), using general enzymatic mechanisms. These assumptions are substantially more general than in previous studies. We show that the steady-state modform concentrations constitute an algebraic variety that can be parameterised by rational functions of the L free enzyme concentrations, with coefficients which are rational functions of the rate constants. The parameterisation allows steady states to be calculated by solving L algebraic equations, a dramatic reduction compared to simulating an exponentially large number of differential equations. This complexity collapse enables analysis in contexts that were previously intractable and leads to biological predictions that we review. Our results lay a foundation for the systems biology of post-translational modification and suggest deeper connections between biochemical networks and algebraic geometry.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Theoretical Biology - Volume 261, Issue 4, 21 December 2009, Pages 626–636
نویسندگان
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