Ultrasensitivity part I: Michaelian responses and zero-order ultrasensitivity

•The simplest signal transduction systems exhibit hyperbolic, michaelian responses.•Sigmoidal, ultrasensitive responses are nevertheless commonplace in cell signaling.•Zero-order ultrasensitivity is one mechanism for producing such responses.•Zero-order ultrasensitivity is probably employed by real signaling systems.

Quantitative studies of signal transduction systems have shown that ultrasensitive responses – switch-like, sigmoidal input/output relationships – are commonplace in cell signaling. Ultrasensitivity is important for various complex signaling systems, including signaling cascades, bistable switches, and oscillators. In this first installment of a series on ultrasensitivity we survey the occurrence of ultrasensitive responses in signaling systems. We review why the simplest mass action systems exhibit Michaelian responses, and then move on to zero-order ultrasensitivity, a phenomenon that occurs when signaling proteins are operating near saturation. We also discuss the physiological relevance of zero-order ultrasensitivity to cellular regulation.