Adenylate Cyclase Cyclic AMP Second Messenger System

Cyclic adenosine monophosphate (abbreviated cAMP) was the first "second messenger" to be discovered and is the best understood. When epinephrine and norepinephrine bind to their P-adrenergic receptors (chapter 9), the effects of these hormones are due to cAMP production within the target cells. It was later discovered that the effects of many (but not all) polypeptide and glycoprotein hormones are also mediated by cAMP.

When one of these hormones binds to its receptor protein, it causes the dissociation of a subunit from the complex of G-proteins (discussed in chapter 7; see table 7.7). This G-protein subunit moves through the membrane until it reaches the enzyme adeny-late (or adenylyl) cyclase (fig 11.8). The G-protein subunit then binds to and activates this enzyme, which catalyzes the following reaction within the cytoplasm of the cell:

Adenosine triphosphate (ATP) is thus converted into cyclic AMP (cAMP) and two inorganic phosphates (pyrophosphate, abbreviated PPj). As a result of the interaction of the hormone with its receptor and the activation of adenylate cyclase,

Fox: Human Physiology, Eighth Edition

11. Endocrine Glands: Secretion and Action of Hormones

Text

© The McGraw-H Companies, 2003

Endocrine Glands

Receptor protein

Hormone

Receptor protein

Hormone

Action Hormones

G-proteins

Adenylate cyclase

Plasma membrane

G-proteins

Adenylate cyclase

Plasma membrane

Adenylyl Cyclase Protein Kinase

Inhibitory subunit

Protein kinase (inactive)

Inhibitory subunit cAMP

Inhibitory subunit

Protein kinase (inactive)

Inhibitory subunit cAMP

Protein kinase

(active)

Phosphorylation of proteins

Activation of specific enzymes

Inactivation of specific enzymes

■ Figure 11.8 The adenylate cyclase-cyclic AMP second-messenger system. The hormone causes the production of cAMP within the target cell cytoplasm, and cAMP activates protein kinase. The activated protein kinase then causes the activation or inactivation of a number of specific enzymes. These changes lead to the characteristic effects of the hormone on the target cell.

therefore, the intracellular concentration of cAMP is increased. Cyclic AMP activates a previously inactive enzyme in the cytoplasm called protein kinase. The inactive form of this enzyme consists of two subunits: a catalytic subunit and an inhibitory subunit. The enzyme is produced in an inactive form and becomes active only when cAMP attaches to the inhibitory subunit. Binding of cAMP to the inhibitory subunit causes it to dissociate from the catalytic subunit, which then becomes active (fig. 11.8). In summary, the hormone—acting through an increase in cAMP production—causes an increase in protein kinase enzyme activity within its target cells.

Active protein kinase catalyzes the phosphorylation of (attachment of phosphate groups to) different proteins in the target cells. This causes some enzymes to become activated and others to become inactivated. Cyclic AMP, acting through protein ki-nase, thus modulates the activity of enzymes that are already present in the target cell. This alters the metabolism of the target tissue in a manner characteristic of the actions of that specific hormone (table 11.4).

Table 11.4 Sequence of Events Involving Cyclic AMP as a Second Messenger

1. The hormone binds to its receptor on the outer surface of the target cell's plasma membrane.

2. Hormone-receptor interaction acts by means of G-proteins to stimulate the activity of adenylate cyclase on the cytoplasmic side of the membrane.

3. Activated adenylate cyclase catalyzes the conversion of ATP to cyclic AMP (cAMP) within the cytoplasm.

4. Cyclic AMP activates protein kinase enzymes that were already present in the cytoplasm in an inactive state.

5. Activated cAMP-dependent protein kinase transfers phosphate groups to (phosphorylates) other enzymes in the cytoplasm.

6. The activity of specific enzymes is either increased or inhibited by phosphorylation.

7. Altered enzyme activity mediates the target cell's response to the hormone.

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Responses

  • arnor
    Where is cyclic amp on plasma membrane?
    7 years ago
  • destiny
    Which hormones use adenyl cyclase as second messsenger?
    7 years ago
  • Mary Ward
    How cyclic amp is produced within a target cell?
    6 years ago
  • lionella
    What is the name of the enzyme that inactivates cyclic adenosine monophosphate?
    6 years ago
  • sirja mett
    What causes an enzyme system to become inactivated?
    6 years ago
  • eberardo
    When a g protein becomes activated and causes an activation of enzymes?
    6 years ago
  • Fulgenzia
    Which of the following substances inactivates cyclic AMP?
    5 years ago
  • Tuulikki
    WHAT IS THE H ORMONE THAT BINDS TO MEMBRANE RECEPTOR ON ON THE CYCLIC ADENOSINE PHOSPHATE?
    5 years ago
  • Tanja
    What is the enzyme that inactivates cyclic adenosine monophoshate?
    5 years ago
  • SUMMER
    Which hormone use cyclic amp?
    5 years ago
  • Sandra
    What us the second messengerwhat enzyme inactivates camp?
    5 years ago
  • maureen
    What is the first messenger in the conversion of atp to camp?
    5 years ago
  • Matthias
    What is the sequence of the cAMP second messenger system?
    2 years ago
  • Idris
    Why ATP convert into cyclic AMP?
    2 years ago
  • Mulu
    Which hormones uses adenyl cyclase cAmp messenger system?
    1 year ago
  • felix fuchs
    Which hormone activates enzyme adenylate cyclase?
    1 year ago
  • ollie
    What are the enzymes that are activated by cyclic AMP?
    3 months ago

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