title: Apoptosis: an optimization approach.
abstract: The present study examined the levels of procaspases (zymogens of the main apoptosis enzymes, caspases) that are predicted based on application of the optimization principle. Optimization models have previously been successfully developed for many other physiological systems (e.g., circulation, oxygen transport system, fibrinolysis, and blood coagulation) but have not previously been applied to apoptotic biochemical pathways. Our model assumed that apoptotic pathways are designed to minimize protein consumption. Procaspase concentrations were predicted based on this assumption, along with known schemes of apoptosis reactions and kinetic constants for procaspase activation and target cleavage. Good agreement between the model predictions and actual procaspase levels was observed.
authors.affiliation: Mathematical Modeling Laboratory, Center for Theoretical Problems of Pharmacology, Russian Academy of Sciences, Marshal Konev Str. 16/34, Moscow 23060, Russia. khanin@softel.ru
authors.forename: Michael A
authors.initials: MA
authors.lastname: Khanin
authors.forename: Aleksey N
authors.initials: AN
authors.lastname: Lobanov
authors.forename: Scott H
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D004792:Enzyme Precursors / Q000378:metabolism; D007700:Kinetics; D008962:Models, Theoretical
chemical_list: D004792:Enzyme Precursors; D020169:Caspases