Adenylate cyclase

In this case, the adenylate cyclase system is considered as an example of the action of adrenaline on liver cells. Adrenaline causes an effect in the body called “fight or flee” (hit or run) - muscle tone increases, heart rate increases. To mobilize the body, an increase in the concentration of glucose in the blood is required. The binding of adrenaline to receptors on the surface of liver cells triggers the breakdown of glycogen stored in liver cells and the release of glucose. ^[5]

Activation

• Adrenaline binds to a β2-adrenergic receptor on the plasma membrane of liver cells. As a result of ligand binding from the outside of the plasma membrane, the conformation of the entire adrenergic receptor changes and the intracellular G-protein conjugated to the adrenergic receptor is activated.
• In the inactive state, the G protein is bound to the HDF molecule. After activation, HDF is replaced by GTP, and the G-protein is divided into two parts (into α- and βγ-subunits).
• The active part of the G-protein (α-subunit) joins the enzyme adenylate cyclase and activates it. Adenylate cyclase catalyzes the conversion of ATP to cAMP .
• cAMP - is the secondary mediator of this signal transmission chain in the cell. Then, cAMP spreads throughout the cell and binds to cAMP-dependent protein kinase A , with 4 cAMP molecules being bound to one protein kinase molecule.
• Activated protein kinase A is divided into four parts, two of which have catalytic activities. Each of the catalytic subunits is able to phosphorylate phosphorylase kinase , activating it.
• Finally, phosphorylase kinase phosphorylates glycogen phosphorylase
• Activated glycogen phosphorylase breaks down glycogen, and glucose-6-phosphate is formed, which is then dephosphorylated and converted to glucose, which enters the bloodstream.

A feature of this signal transmission system in the cell is that the signal is amplified at most stages (except for the activation of protein kinases A by cAMP molecules), for example, activated adenylate cyclase synthesizes many cAMP molecules. As a result of the interaction of one adrenaline molecule with a receptor in the plasma membrane of a liver cell, about 10 million glucose molecules are released into the blood. ^[one]

Inactivation

To maintain the correct metabolic rate, not only a quick flow of glucose into the blood is required, but also a shutdown mechanism for this system. There are several ways to do this.

• When the concentration of adrenaline in the blood decreases, the adrenaline molecules naturally disconnect from the β2-adrenoreceptor
• If adrenaline is not disconnected from the β2-adrenergic receptor, then the receptor is phosphorylated by the kinase of the β2-adrenergic receptor, and then inactivated by β- arrestin
• G-protein itself has enzymatic activity and slowly (within seconds or minutes) converts GTP to GDF. After that, he departs from adenylate cyclase, and it is inactivated
• The enzyme phosphodiesterase catalyzes the conversion of cAMP to AMP
• Phosphatase enzymes dephosphorylate phosphorylase kinase and glycogen phosphorylase ^[1] .

The effect of adrenaline on other types of cells depends on which receptors are in their plasma membranes. So, for example, as a result of the binding of adrenaline to the alpha-2 adrenergic receptor , the amount of cAMP inside the cell decreases.

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