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The Cyclic AMP System

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Enzymes in Anesthesiology
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Abstract

Cyclic 3′, 5′-adenosine monophosphate (cAMP), a nucleotide present in small amounts in almost every type of mammalian cell, has a key role in the regulation of many processes in the body. Cyclic AMP was discovered by E. W. Sutherland almost 20 years ago in the course of studies of the hyperglycemic effect of epinephrine. Sutherland postulated that in order to increase hepatic glucose output epinephrine must increase the activity of the rate-limiting enzyme involved in the conversion of glycogen to glucose. This enzyme was identified as phosphorylase, which catalyzes the hydrolysis of glycogen to glucose 1-phosphate. Indeed, the addition of epinephrine to a liver slice or preparation of ruptured liver cells produced an increase in phosphorylase activity. However, when phosphorylase was partially purified, epinephrine did not increase enzyme activity, an observation that led to the assumption that the hormone does not activate phosphorylase directly but exerts its effect at a step prior to the activation of the enzyme. When fragments of cell membrane were exposed to epinephrine, boiled, and added to purified phosphorylase, its activity increased. Epinephrine evidently interacted with an enzyme present in the cell membrane producing a heat-stable compound that in turn activated phosphorylase. The heat-stable compound was identified by Sutherland as cAMP in 1957, and the enzyme with which epinephrine interacts was identified as adenylate cyclase in 1962.

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Triner, L. (1978). The Cyclic AMP System. In: Foldes, F.F. (eds) Enzymes in Anesthesiology. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-6248-0_11

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  • DOI: https://doi.org/10.1007/978-1-4612-6248-0_11

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