Regulatory Cascade


An enzyme cascade is a regulatory system where one enzyme catalyses the covalent modification of another enzyme. Regulatory cascades are either unidirectional or cyclic; both types are important biological switches for the regulation of physiological processes.

Keywords: cascades; protein phosphorylation; proteolysis; glycogen metabolism; blood clotting

Figure 1.

Monocyclic cascade.

Figure 2.

Control of glycogen metabolism by reversible enzyme phosphorylation. Gα, α subunit of trimeric G protein; AC, adenylyl cyclase (subscripts i and a indicate inactive and activated forms of the interconvertible enzyme); PhbK, phosphorylase kinase; G1P, glucose 1‐phosphate; G6P, glucose 6‐phosphate; UDPG, uridine diphosphate glucose; Phos a/b, glycogen phosphorylase a/b; Sy a/b, glycogen synthase a/b; Inh‐1, phosphatase inhibitor 1; P, phosphate.

Figure 3.

Mechanism of blood clotting.



Bollen M, Keppens S and Stalmans W (1998) Specific features of glycogen metabolism in the liver. Biochemical Journal 336: 19–31.

Chock PB and Stadtman ER (1996) Cyclic cascade in cellular regulation. In: Bittar EE and Bittar N (eds) Principles of Medical Biology, vol. 4: Cell Chemistry and Physiology, part II, pp. 201–220. Greenwich, CT: Jai Press.

Davie EW and Fujikawa K (1975) Basic mechanisms in blood coagulation. Annual Review of Biochemistry 44: 799–829.

Goldbeter A and Koshland DE Jr (1987) Energy expenditure in the control of biochemical systems by covalent modification. Journal of Biological Chemistry 262: 4460–4471.

Neurath H and Walsh KA (1976) In: Ribbons EW and Brew K (eds) Proteolysis and Physiological Regulation, pp. 29–40. New York: Academic Press.

Shacter E, Stadtman ER, Jurgensen SR and Chock PB (1988) Role of cAMP in cyclic cascade regulation. Methods in Enzymology 159: 3–19.

Stadtman ER and Chock PB (1978) Interconvertible enzyme cascades in metabolic regulation. Current Topics in Cellular Regulation 13: 53–95.

Further Reading

Bollen M, Keppens S and Stalmans W (1998) Specific features of glycogen metabolism in the liver. Biochemical Journal 336: 19–31.

Davie EW, Fujikawa K and Kisiel W (1991) The coagulation cascade: initiation, maintenance and regulation. Biochemistry 30: 10363–10370.

Goldbeter A and Wolpert L (1990) Covalent modification of proteins as a threshold mechanism in development. Journal of Theoretical Biology 142: 243–250.

Schulz AR (1998) Control analysis of muscle glycogen metabolism. Archives of Biochemistry and Biophysics 353: 172–180.

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Lint, Johan Van, and Vandenheede, Jackie R(Apr 2001) Regulatory Cascade. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1038/npg.els.0000867]