MCQ Physiology Answer 3

Answer: 2. Inhibiting the conversion of Gs-GTP to Gs-GDP

Review:
Many extracellular substances cause intracellular actions via second-messenger system. These second messengers may bind to the receptors that are located either on the surface of the cell or within the cell itself. Substances that react withintracellular receptors are lipid-soluble (lipophillic) molecules that can pass through the lipid plasma membrane. Examples of these lipophillic substances include thyroid hormones, steroid hormones,and the fat soluble vitamins A and D. Once inside the cell they generally travel to the nucleus and bind to the Hormone Response Element(HRE) of DNA.

Some substances that react to with the cell surface receptors bind to the guanine nucleotide regulatory proteins. These proteins, called G-proteins, may be classified into:

1. Gs - Regulates intracellular conc. of cyclic adenosine 5'-monophosphate (cAMP)
   
2. Gi - Regulates intracellular conc. of cyclic adenosine 5'-monophosphate (cAMP)
3. Gt - Regulates intracytoplasmic levels of (cGMP)
   
4. Gq - Regulates intracytoplasmic levels of Calcium ions.

Gs and Gi regulate cAMP levels by their actions on the adenyl cyclase enzyme located on the inner surface of the plasma membrane that catalyzes the formation of AMP from ATP.
The adenylate cyclase G-protein complex is composed of the following components:

1. The Receptor
2. The catalytic enzyme (adenyl cyclase)
3. Coupling Unit - Consists of GTP- dependent regulatory proteins (G proteins), which may be stimulatory (Gs) or inhibitory (Gi).

When bound to GTP and active, Gs stimulates adenyl cyclase and increases cAMP levels. (Gs is an "on Switch")
In contrast Gi inhibits adenyl cyclase and decrease cAMP levels . (Gi is an "off Switch")

Both cholera toxin and pertussis toxins act via the adenyl cyclase pathway.

Cholera inhibits conversionof Gs-GTP to Gs-GDP i.e keeps on switch in the on position.
Pertussis inhibits the activation of Gi-GDP to Gi-GTP i.e. Keeps the off switch in the off position.

Category: Physiology MCQs