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• W2023363172 abstract "•The previous installments in this series reviewed several mechanisms for generating ultrasensitivity. •In this review, we examine how ultrasensitivity can contribute to the functioning of more complex systems. •Ultrasensitivity can allow cascades to transmit signals effectively. •Ultrasensitivity is important for the generation of bistability by positive feedback loops. •Ultrasensitivity promotes the generation of limit cycle oscillations by negative feedback loops. Switch-like, ultrasensitive responses – responses that resemble those of cooperative enzymes but are not necessarily generated by cooperativity – are widespread in signal transduction. In the previous installments in this series, we reviewed several mechanisms for generating ultrasensitivity: zero-order ultrasensitivity; multistep ultrasensitivity; inhibitor ultrasensitivity; and positive feedback (or double negative feedback) loops. In this review, we focus on how ultrasensitive components can be important for the functioning of more complex signaling circuits. Ultrasensitivity can allow the effective transmission of signals down a signaling cascade, can contribute to the generation of bistability by positive feedback, and can promote the production of biochemical oscillations in negative feedback loops. This makes ultrasensitivity a key building block in systems biology and synthetic biology. Switch-like, ultrasensitive responses – responses that resemble those of cooperative enzymes but are not necessarily generated by cooperativity – are widespread in signal transduction. In the previous installments in this series, we reviewed several mechanisms for generating ultrasensitivity: zero-order ultrasensitivity; multistep ultrasensitivity; inhibitor ultrasensitivity; and positive feedback (or double negative feedback) loops. In this review, we focus on how ultrasensitive components can be important for the functioning of more complex signaling circuits. Ultrasensitivity can allow the effective transmission of signals down a signaling cascade, can contribute to the generation of bistability by positive feedback, and can promote the production of biochemical oscillations in negative feedback loops. This makes ultrasensitivity a key building block in systems biology and synthetic biology. having two stable steady states for a single value of the input, as contrasted with a monostable response. in the present context, it is an algebraic equation of the form Xtot = X1 + X2 + ..., where species X is interconverted among various forms (X1, X2....) but the total concentration of X (Xtot) does not change with respect to time. a characteristic of some multistep processes where completing some of the early steps makes a later step more favorable. Examples include the multistep binding of oxygen to hemoglobin and priming in multisite phosphorylation. effective concentration 50; the concentration of a stimulus required for a half-maximal (50%) response. an input-output relationship of the form Output=InputnKn+Inputn, where n is the Hill exponent or Hill coefficient. The larger the Hill exponent, the more ultrasensitive the response. a simple kinetic scheme where the rate of a reaction is directly proportional to the concentration of the substrate or substrates involved in the reaction. This contrasts with Michaelis–Menten kinetics or kinetic schemes involving Hill functions. a model for the rate of an enzymatic reaction, premised on the assumption that the enzyme is small in concentration compared to its substrate, and that the concentration of the enzyme-substrate complex is unchanging with respect to time. In the Michaelis–Menten model the rate of an enzymatic reaction is given by: dProductdt=VmaxSubstrateKm+Substrate. a hyperbolic relationship between the input to a system and its steady-state response, described by an equation of the form Output=InputEC50+Input. The equation for the response resembles the Michaelis–Menten equation (above), hence the name. Note though that a Michaelian response is obtained when the activities of the enzymes that produce the output are described by the law of mass action, not the Michealis–Menten equation. See Part 1 of this series [1Ferrell Jr, J.E. Ha S.H. Ultrasensitivity part I: Michaelian responses and zero-order ultrasensitivity.Trends Biochem. Sci. 2014; 39: 496-503Abstract Full Text Full Text PDF PubMed Scopus (124) Google Scholar] for further discussion. having one stable steady-state output for each value of the input, as contrasted with bistable or multistable responses. having two or more stable steady-state output for each value of the input, as contrasted with a monostable response. a type of limit cycle oscillator with a bistable trigger, where one slowly changing species causes a second rapidly-changing species to switch between discrete states. a property of steady-state input-output relationships that makes them switch-like in character. Goldbeter and Koshland defined input-output relationships to be ultrasensitive if it took less than an 81-fold change in input stimulus to drive the output from 10% to 90% of maximum. a zero-order chemical or biochemical reaction is one where the rate of the reaction is independent of the substrate concentration. Enzyme reactions approach zero-order when the enzyme is saturated with substrate." @default.
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• W2023363172 date "2014-12-01" @default.
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• W2023363172 title "Ultrasensitivity part III: cascades, bistable switches, and oscillators" @default.
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• W2023363172 doi "https://doi.org/10.1016/j.tibs.2014.10.002" @default.
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