The mechanism of activation of adenylate cyclase and production of cAMP can be d
ID: 178428 • Letter: T
Question
The mechanism of activation of adenylate cyclase and production of cAMP can be described as (page 81 of your handout book): L + R doubleheadarrow_k_r^k_f C, C + E doubleheadarrow_k_u^k_c E - C rightarrow^k_a E * + C (rightarrow^k_d E + C) To develop the model, steady-state kinetic experiments were performed to understand the activation of the enzyme adenylate cyclase as function of time, ligand concentrations, receptor numbers on the cellular surface, and enzyme numbers (results were shown as Figure 5-6 and Figure 5-7 on pages 81-82 of your handout book). These experiments were designed to probe the kinetics of activation of enzyme and accumulation of cAMP during period of steady state receptor/ligand binding to the beta-adrenergic receptor on erythrocytes. All experiments were performed in the presence of GppNHp which is the non-hydrolyzable GTP analog preventing the deactivation of activated G-proteins. Please provide a rationale and a brief description how (1) concentrations of ligand (L- epinephrine), (2) numbers of receptor (beta-adrenergic receptor), (3) numbers of the activated enzyme (adenylate ayclase), and (4) level of the activated G-protein could be controlled in these measurements.Explanation / Answer
1) Ligand is epinephrine/adrenaline. This ligand plays important role in 'fight and flight'. This hormone is produced by the adrenal glands, during stress condition in our body. ACTH of pituitary stimulates adrenal medulla to release this hormone at the time of stress. So, concentration of ligand can be controlled by:
2) Receptor number cannot be controlled. Beta-2 adrenergic receptors are present on the cell membrane; only the number of ligands can be controlled.
4) Level of G-protein can be controlled by those factors which control binding of GTP to these proteins. These factors are "ligand" and "receptor". After this binding, a conformational change occurs in G-protein; as a result, GTP binds to G-protein instead of GDP.
3) Numbers of Adenylate cyclase (activated enzyme) are again be controlled by G-proteins; which in turn are controlled by receptor and ligand.
So, the numbers of all the four above are controlled by the concentration of each other.