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Ultrasensitivity in biochemical systems controlled by covalent modification. Interplay between zero-order and multistep effects.

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      A previous analysis of covalent modification systems (Goldbeter, A., and Koshland, D. E., Jr. (1981) Proc. Natl. Acad. Sci. U. S. A. 78, 6840-6844) showed that steep transitions in the amount of modified protein can occur when the converter enzymes are saturated by their protein substrate. This “zero-order ultrasensitivity” can further be amplified when an effector acts at more than one step in a monocyclic or multicyclic cascade of covalent modification. We analyze the limitations of the latter “multistep ultrasensitivity” and show how it can combine with the zero-order effect to enhance the sensitivity of biochemical systems controlled by covalent modification.

      REFERENCES

        • Koshland Jr., D.E.
        • Goldbeter A.
        • Stock J.B.
        Science (Wash. D. C.). 1982; 217: 220-225
        • Goldbeter A.
        • Koshland Jr., D.E.
        Proc. Natl. Acad. Sci. U. S. A. 1981; 78: 6840-6844
        • Bohr C.
        • Hasselbach K.
        • Krogh A.
        Arch. Physiol. 1904; 16: 402-407
        • Hill A.V.
        Biochem. J. 1913; 4: 471-480
        • Levitzki A.
        • Koshland Jr., D.E.
        Curr. Top. Cell Regid. 1976; 10: 2-40
        • Krebs E.G.
        • Fisher E.H.
        Biochem. Biophys. Acta. 1956; 20: 150-157
        • Cohen P.
        Control of Enzyme Activity. Chapman and Hall, London1983
        • Chock P.B.
        • Stadtman E.R.
        Proc. Natl. Acad. Sci. U. S. A. 1977; 24: 2766-2770
        • Chock P.B.
        • Rhee S.G.
        • Stadtman E.R.
        Annu. Rev. Biochem. 1980; 49: 813-843
        • Goldbeter A.
        • Koshland Jr., D.E.
        Q. Rev. Biophys. 1982; 15: 555-591
        • LaPorte D.
        • Koshland Jr., D.E.
        Nature (Load.). 1983; 305: 286-290
        • Koshland Jr., D.E.
        • Nemethy G.
        • Filmer D.
        Biochemistry. 1966; 5: 365-385
        • Teipel J.
        • Koshland Jr., D.E.
        Biochemistry. 1969; 8: 4656-4663
        • Cohen P.
        Molecular Aspects of Cellular Regulation. Vol. 1. Elsevier, New York1980: 255-268
        • Builder S.E.
        • Beavo J.A.
        • Krebs E.G.
        J. Biol Chem. 1980; 255: 3514-3519

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