In studies trying to understand the regulation of hormone-sensitive adenylate cy

Question

In studies trying to understand the regulation of hormone-sensitive adenylate cyclase, it was discovered that non-hydrolyzable GTP analogs and cholera toxin (that inhibits the GTPase activity of Gs) were able to activate the enzyme in a sustained (irreversible) profile, therefore indicating that GTP hydrolysis represents a deactivation (turn-off) regulatory step. PLEASE ANSWER CLEARLY with full explanation. thanks

a) Will these analogs or toxin have any effect on adenylate cyclase activity in the absence of any added hormone?

b) If you add an factor that increases the rate of GTPase hydrolysis of the Gs protein, will this activate or inhibit the observed downstream effect upon addition of the hormone (this is in the absence of GTP analogs or toxin). Explain your answer.

Explanation / Answer

Based on the given data, Cholera toxin is made up of five identical B subunits and one “A subunit.” In causing cholera, first one of the B subunits of cholera toxin binds to a glycolipid receptor in the cytoplasmic membrane of an intestinal epithelial cell. Then, when the A subunit is cleaved, a portion of it known as A1 enters the cell’s cytosol, acting as an enzyme and activating adenylate cyclase.

After adenylate cyclase is activated, it enzymatically converts ATP (adenosine triphosphate) into cyclic AMP (cAMP), which stimulates secretion of excess levels of electrolytes from the cell. Through osmosis, water follows the electrolytes out of the cell into the intestinal lumen. This process results in the severe diarrhoea characterizing cholera.

a)

Yes, in the absence of any added hormone the GTP analogs, like Gpp(NH)p, Gpp(CH2)p and GTPyS and cholera toxin Increases the activity of the enzyme and the action of hormone is potentiated.

b)

The activity of enzyme adenylate cyclase requires GTP nucleotides. If we add actor that increases the rate of GTPase hydrolysis of the Gs protein, then it will degrade all GTPs. It results unavailability of GTP to adenylate cyclase. Therefore, it will inhibit the observed downstream effect upon addition of the hormone.      

Related Questions

Navigate

• Browse (All)
• Browse I
• Subjects

Integrity-first tutoring: explanations and feedback only — we do not complete graded work. Learn more.