Biochem Chp 13 & 15 Review

What is Step 1 in a signal transduction pathway?

signal: a primary messenger is released in response to physiological change

What is Step 2 in a signal transduction pathway?

reception: primary messenger is received by integral membrane protein (receptor) and receptor undergoes conformational change upon binding; amplification occurs during which the signal is mass produced by secondary messengers

What is Step 3 in a signal transduction pathway?

transduction: secondary messenger relays detection of primary messenger and activates effector muscles to initiate physiological responses

What is Step 4 in a signal transduction pathway?

termination: end of the signal cascade

What are some common second messengers?

cyclic AMP (cAMP), cyclic GMP (cGMP), calcium ion, diacylglycerol (DAG), and inositol 1,4,5-triphosphate (IP₃)

What are the three major classes of membrance receptors?

• seven transmembrane helix receptors (7TM); i.e. epinephrine and glucagon

• dimeric receptors that recruit protein kinases; i.e. human growth hormone

• dimeric receptors that are protein kinases; i.e. insulin receptor

Explain the mechanism of 7TM receptors:

• beta-adrenergic receptor is activated by binding to epinephrine, activates heterotrimeric G-protein

• activated G-protein ejects GDP and replaces it with GTP

• alpha subunit dissociates from beta-gamma dimer, which can now interact with other things

Explain what an activated G-protein does:

• termed Gas, the protein stimulates adenylate cyclase

• activation of the cyclase synthesizes cAMP

• cAMP then activates protein kinase A (PKA)

Explain the structure of protein kinase A:

consists of two pairs of subunits: catalytic (C) and regulatory (R); binding of cAMP to the R subunits cause dissociation and activation of C subunits

What is the role of activated C subunits?

continues the epinephrine signal transduction pathway by phosphorylating additional protein targets that alter physiological functions of the cell

How do G-proteins terminate?

• through inherent GTPase activity that cleaves the bound GTP to GDP so that the protein spontaneously reassociates with the beta-gamma subunits

• phosphodiesterase converts cAMP to AMP, no longer activating PKA

• concentration of epinephrine declines, leaving receptor inactive

Clinical Insight: How does altered G-protein activity cause cholera?

choleragen (bacterial toxin), modifies Gas protein and traps it in the active GTP form → overstimulation of PKA → excessive loss of NaCl and water in intestines