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Elusive control
Authors:Hans V Westerhoff  Boris N Kholodenko  Marta Cascante  Karel Van Dam
Institution:(1) Department of Microphysiology, Faculty of Biology, Free University, De Boelelaan 1087, NL-1081 HV Amsterdam, The Netherlands;(2) E. C. Slater Institute, University of Amsterdam, Amsterdam, The Netherlands;(3) Belozersky Institute, Moscow State University, Moscow, Russia;(4) Department of Biochemistry and Physiology, University of Barcelona, Barcelona, Spain
Abstract:The concept of a single rate-limiting step was proven to be too simplistic for understanding control and regulation of metabolism. Consequently, searches have identified relatively few steps with high control. Here we review a number of such searches and indicate what mechanisms may be responsible for this elusiveness of control. It turns out that this elusiveness of control has itself led to increased understanding of the roles played in metabolic control and regulation of such diverse factors as distributiveness of control, condition dependence, enzyme elasticity, homeostasis, control hierarchies, the input into a pathway, coenzyme sequestration, and redundancy and diversity of control function.
Keywords:Metabolic control  analysis  and regulation  control hierarchies  channelling  homeostasis  enzyme organization
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