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- Explain how the pKa for histidine 57 is important to its role in the mechanism of chymotrypsin actionWhat effect does binding of the IRF protein to the IRE in the mRNA encoding ferritin have on the production of ferritin? Briefly explain why this effect is observed.Describe the general function and structural features of G-protein-coupled receptors (GPCRs). Be sure to include an explanation of GTPase activating proteins (GAPs) and GDP exchange factors (GEFs) in the context of the GTPase cycle. How are different classes of heterotrimeric G-proteins defined?
- In response to nitric oxide signaling in the male genitalia, GTP is cyclized to produce 3’-5’ cyclic GMP (cGMP): cGMP stimulates vasodilation and produces an erection. Viagra (Sildenafil) is a selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP. Based on this information, do you expect that Viagra can produce a spontaneous erection in the absence of a stimulus? Provide a short (one sentence) rationale for your answerDescribe the similarities and differences in the structures of GPCRs specific for various ligands including the extracellular , transmembrane , and intracellular domains.GTP-binding proteins play critical roles in many signal transductions through G proteins. Describe two examples in which G proteins act and compare the role of the G proteins in each case.
- Describe the role of pH in regulating the interaction between mannose 6-phosphate and the M6P receptor. Why does a rise in endosomal pH lead to the secretion of newly synthesized lysosomal enzymes into the extracellular medium?Describe the path for the synthesis of TTP from UTP.Describe the mechanisms that limit signaling by the phosphoinositide pathway.
- Explain the regulatory processes of purine synthesis that would result in an increase in the concentration of GMP.In studies trying to understand the regulation of hormone-sensitive adenylatecyclase, it was discovered that non-hydrolyzable GTP analogs and cholera toxin (that inhibits theGTPase activity of Gs ) were able to activate the enzyme in a sustained (irreversible) profile, thereforeindicating that GTP hydrolysis represents a deactivation (turn-off) regulatory step.a) Will these analogs or toxin have any effect on adenylate cyclase activity in the absenceof any added hormone?b) If you add an factor that increases the rate of GTPase hydrolysis of the Gs protein, willthis activate or inhibit the observed downstream effect upon addition of the hormone (this is in theabsence of GTP analogs or toxin). Explain your answer.Explain why in cells that are genetically NF1–/–, basal levels of GTP-bound activated Ras are higher than normal and respond to growth factor stimulation by increasing rapidly to far higher levels.