Adrenaline cAMP formation

The next key point is to realize that each enzyme in the pathway exists in both active and inactive forms. cAMP initiates a cascade of reactions by activating protein kinase A (PK-A)," the active form of which activates the next enzyme in the sequence, and so on. At the end of the day, glycogen phosphorylase is activated and glucose or ATP is produced. This signaling pathway is a marvelous amplification system. A few molecules of glucagon or adrenaline may induce formation of many molecules of cAMP, which may activate many of PK-A, and so on. The catalytic power of enzymes is magnified in cascades of this sort. 

Activation of Gs or Gi proteins results in stimulation or inhibition, respectively, of adenylyl cyclase which catalyses the formation of cyclic adenosine monophosphate (cAMP) from ATP The cAMP binds to protein kinase A (PKA), which mediates the diverse cellular effects of cAMP by phosphorylating substrate enzymes, thereby increasing their activity. Among the responses mediated by cAMP are increases in contraction of cardiac and skeletal muscle and glycogenolysis in the liver by adrenaline (epinephrine). Because a single activated receptor can cause the conversion of up to 100 inactive Gs proteins to the active form, and each of these results in the synthesis of several hundred cAMP molecules, there is a very considerable signal amplification. For example, adrenaline concentrations as low as 10-10 M can stimulate the release of glucose sufficient to increase... 

A well-studied example of a signal response, mediated by a heterotrimeric G protein, is the activation of the enzyme adenylyl cyclase by the hormone adrenaline. Adenylyl cyclase catalyses formation of cAMP from ATP (Fig. 5.2). 

Hormone-sensitive lipase tissue activity is stimulated by adrenaline (epinephrine), glucagon, ACTH (corticotropin), TSH (thyrotropin) and serotonin (Jensen, 1971). These hormones are presumed to exert their effects on adipose tissue by stimulating adenylate cyclase. Certainly, an increased formation of cAMP (cyclic AMP) is brought about by lipolytic hormones and cAMP has been shown to stimulate lipase activity in cell-free preparations (cf. O Doherty, 1978). 

One of the intracellular effectors that is activated by the (G-protein a-subunit)-GTP complex is adenylyl cyclase. This is an integral membrane protein which catalyses the formation of cyclic AMP (cAMP) from ATP (Figure 10.8). cAMP then acts as the second messenger in response to hormones such as glucagon and adrenaline. It is an allosteric activator of protein kinases. cAMP is also formed in the same way in response to a number of neurotransmitters. 

Adrenaline, released from the adrenal glands in response to fear or fright, acts on cell-surface receptors, leading to the formation of cAMP, which leads to increased activity of protein kinase and increased activity of glycogen phosphorylase (see Figure 10.6). 

The system is called an amplification cascade since the binding of one molecule of adrenaline can cause the formation of numerous molecules of cAMP which may dissociate protein kinase A molecules thereby sequentially promoting the activation of more molecules of phosphorylase kinase... 

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