Multi-stage regulation, a key to reliable adaptive biochemical pathways

A general "multi-stage" regulation model, based on linearly connected regul atory units, is formulated to demonstrate how biochemical pathways may achi eve high levels of accuracy. The general mechanism, which is robust to chan ges in biochemical parameters, such as protein concentration and kinetic ra te constants, is incorporated into a mathematical model of the bacterial ch emotaxis network and provides a new framework for explaining regulation and adaptiveness in this extensively studied system. Although conventional the ories suggest that methylation feedback pathways are responsible for chemot actic regulation, the model, which is deduced from known experimental data, indicates that protein interactions downstream of the bacterial receptor c omplex, such as CheAs and CheZ, may play a crucial and complementary role.