Xla

Epinephrine-receptor complex

Hepatocyte

Inactive PKA

x molecules

20x molecules

10x molecules x molecules

20x molecules

10x molecules

Active ^ phosphorylase b / kinase

100x molecules

Active glycogen , phosphorylase a

Glycogen i %

1,000x molecules

Glucose 1-phosphate

Glucose 1-phosphate

Blood glucose

10,000x molecules

Blood glucose

10,000x molecules

FIGURE 12-16 Epinephrine cascade. Epinephrine triggers a series of reactions in hepatocytes in which catalysts activate catalysts, resulting in great amplification of the signal. Binding of a small number of molecules of epinephrine to specific ^-adrenergic receptors on the cell surface activates adenylyl cyclase. To illustrate amplification, we show 20 molecules of cAMP produced by each molecule of adenylyl cyclase, the 20 cAMP molecules activating 10 molecules of PKA, each PKA molecule activating 10 molecules of the next enzyme (a total of 100), and so forth. These amplifications are probably gross underestimates.

kinase activates glycogen phosphorylase b, which leads to the rapid mobilization of glucose from glycogen. The net effect of the cascade is amplification of the hormonal signal by several orders of magnitude, which accounts for the very low concentration of epinephrine (or any other hormone) required for hormone activity.

Cyclic AMP, the intracellular second messenger in this system, is short-lived. It is quickly degraded by cyclic nucleotide phosphodiesterase to 5'-AMP (Fig. 12-12, step ©), which is not active as a second messenger:

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