Properties Needed for the Enzymes of an Interconvertible Cascade to Generate a Highly Sensitive Response

Abstract

One of the important problems in biology is how to produce a sufficiently sensitive response to a signal. An essential point in metabolic control is thus the sensitivity in the response of a pathway to an effector. Consequently the understanding of the mechanisms that allow a high degree of sensitivity should constitute a major goal of any theory of metabolic control. Cooperativity in the response of an enzyme to an effector is undoubtedly an important mechanism, but it appears insufficient as the degree of cooperativity of enzymes is never very high (Hill coefficients less than 4 in nearly all cases). Thus even an effector that acts on a step with a flux control coefficient close to unity would only be able to switch on and off the pathway flux (say between 10% and 90% of full activity) if its concentration increases at least three-fold. Even a Hill coefficient as high as 6, rarely seen in nature, would only lower this ratio to two-fold. Furthermore, as flux control coefficients in reality are usually less than unity, the sensitivity of the pathway to the effector is decreased accordingly.