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Proc Natl Acad Sci U S A. Nov 1981; 78(11): 6840–6844.
PMCID: PMC349147

An amplified sensitivity arising from covalent modification in biological systems.

Abstract

The transient and steady-state behavior of a reversible covalent modification system is examined. When the modifying enzymes operate outside the region of first-order kinetics, small percentage changes in the concentration of the effector controlling either of the modifying enzymes can give much larger percentage changes in the amount of modified protein. This amplification of the response to a stimulus can provide additional sensitivity in biological control, equivalent to that of allosteric proteins with high Hill coefficients.

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  • KREBS EG, FISCHER EH. The phosphorylase b to a converting enzyme of rabbit skeletal muscle. Biochim Biophys Acta. 1956 Apr;20(1):150–157. [PubMed]
  • Krebs EG, Beavo JA. Phosphorylation-dephosphorylation of enzymes. Annu Rev Biochem. 1979;48:923–959. [PubMed]
  • Cohen P. The role of cyclic-AMP-dependent protein kinase in the regulation of glycogen metabolism in mammalian skeletal muscle. Curr Top Cell Regul. 1978;14:117–196. [PubMed]
  • Chock PB, Rhee SG, Stadtman ER. Interconvertible enzyme cascades in cellular regulation. Annu Rev Biochem. 1980;49:813–843. [PubMed]
  • Greengard P. Phosphorylated proteins as physiological effectors. Science. 1978 Jan 13;199(4325):146–152. [PubMed]
  • Uy R, Wold F. Posttranslational covalent modification of proteins. Science. 1977 Dec 2;198(4320):890–896. [PubMed]
  • Springer MS, Goy MF, Adler J. Protein methylation in behavioural control mechanisms and in signal transduction. Nature. 1979 Jul 26;280(5720):279–284. [PubMed]
  • Koshland DE., Jr A model regulatory system: bacterial chemotaxis. Physiol Rev. 1979 Oct;59(4):811–862. [PubMed]
  • Sutherland EW. Studies on the mechanism of hormone action. Science. 1972 Aug 4;177(4047):401–408. [PubMed]
  • Stadtman ER, Chock PB. Superiority of interconvertible enzyme cascades in metabolic regulation: analysis of monocyclic systems. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2761–2765. [PMC free article] [PubMed]
  • Chock PB, Stadtman ER. Superiority of interconvertible enzyme cascades in metabolite regulation: analysis of multicyclic systems. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2766–2770. [PMC free article] [PubMed]
  • Stadtman ER, Chock PB. Interconvertible enzyme cascades in metabolic regulation. Curr Top Cell Regul. 1978;13:53–95. [PubMed]
  • Koshland DE, Jr, Némethy G, Filmer D. Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry. 1966 Jan;5(1):365–385. [PubMed]
  • Perutz MF. Regulation of oxygen affinity of hemoglobin: influence of structure of the globin on the heme iron. Annu Rev Biochem. 1979;48:327–386. [PubMed]
  • Lee EY, Silberman SR, Ganapathi MK, Petrović S, Paris H. The phosphoprotein phosphatases: properties of the enzymes involved in the regulation of glycogen metabolism. Adv Cyclic Nucleotide Res. 1980;13:95–131. [PubMed]
  • DANFORTH WH, HELMREICH E, CORICF The effect of contraction and of epinephrine on the phosphorylase activity of frog sartorius muscle. Proc Natl Acad Sci U S A. 1962 Jul 15;48:1191–1199. [PMC free article] [PubMed]
  • Stalmans W, De Wulf H, Hue L, Hers HG. The sequential inactivation of glycogen phosphorylase and activation of glycogen synthetase in liver after the administration of glucose to mice and rats. The mechanism of the hepatic threshold to glucose. Eur J Biochem. 1974 Jan 3;41(1):127–134. [PubMed]
  • Hers HG. The control of glycogen metabolism in the liver. Annu Rev Biochem. 1976;45:167–189. [PubMed]
  • Schutt H, Holzer H. Biological function of the ammonia-induced inactivation of glutamine synthetase in Escherichia coli. Eur J Biochem. 1972 Mar 15;26(1):68–72. [PubMed]
  • Collett MS, Erikson RL. Protein kinase activity associated with the avian sarcoma virus src gene product. Proc Natl Acad Sci U S A. 1978 Apr;75(4):2021–2024. [PMC free article] [PubMed]
  • Hunter T, Sefton BM. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1311–1315. [PMC free article] [PubMed]
  • Levinson AD, Oppermann H, Levintow L, Varmus HE, Bishop JM. Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein. Cell. 1978 Oct;15(2):561–572. [PubMed]
  • Martiel JL, Goldbeter A. Metabolic oscillations in biochemical systems controlled by covalent enzyme modification. Biochimie. 1981 Feb;63(2):119–124. [PubMed]

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