| | Martin, B.R.Metabolic Regulation: A Molecular Approach. Oxford, UK; Blackwell Scientific, 1987.
Newsholme, E.A.; Start, C.Regulation in Metabolism. New York: Wiley, 1973. |
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| | Cohen, P.Control of Enzyme Activity, 2nd ed. London: Chapman and Hall, 1983.
Koshland, D.E.,Jr. Switches, thresholds and ultrasensitivity. Trends Biochem. Sci. 12:225-229, 1987 |
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|  | Enzymes Can Be Switched On and Off by Covalent Modification22
The types of feedback control just described permit the rates of reaction sequences to be regulated continuously and automatically in response to second-by-second fluctuations in metabolism. Cells have different devices for regulating enzymes when longer-lasting changes in activity, occurring over minutes or hours, are required. These involve reversible covalent modification of enzymes. This modification is usually, but not always, accomplished by the addition of a phosphate group to a specific serine, threonine, or tyrosine residue in the enzyme. The phosphate comes from ATP, and its transfer is catalyzed by a family of enzymes known as protein kinases.
In Chapter 5 we describe how phosphorylation can alter the shape of an enzyme in such a way as to increase or inhibit its activity. The subsequent removal of the phosphate group, which reverses the effect of the phosphorylation, is achieved by a second type of enzyme, called a protein phosphatase. Covalent modification of enzymes adds another dimension to metabolic control because it allows specific reaction pathways to be regulated by extracellular signals (such as hormones and growth factors) that are unrelated to the metabolic intermediates themselves.
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