1. Research in cell biology and metabolism has progressed due to the discovery o

Question

1. Research in cell biology and metabolism has progressed due to the discovery of molecules that artificially stimulate or inhibit glucagon/epinephrine and insulin signaling pathways. Let's say you are working in a lab cataloging the effects of a library of small molecules on these pathways and have a "hit" on molecule 1stAVNGR. Preliminary data on molecule IstAVNGR indicates that the cardiac isoform of PFK2/FBPase2 is doubly phosphorylated when this molecule is present at micromolar concentrations in cell cultures. Given this context answer the following questions. Under these conditions what is the predicted degree of association between the regulatory subunits and the catalytic subunits of PKA? (1 point) a. b. Further investigation of molecule 1stAVNGR indicates elevated levels of cAMP within the cell despite the absence of epinephrine or glucagon. Hypothesize two possible explanations for this data. (4 points) When cell cultures are given both molecule IstAVNGR and molecule RedSKLL (a G-protein inhibitor) cAMP levels remain high (again despite the absence of epinephrine or glucagon). Given this new information hypothesize a possible explanation for the data. (2 points) c.

Explanation / Answer

For this exercise it is necessary to know that PFK is an enzyme that catalyzes the conversion of fructose 6 phosphate to fructose 1,6-bisphosphate. Additionally this enzyme is the most important cotrol element of glycolysis in mammals. This enzyme is inhibited in an allosteric way by high levels of ATP (that is to say that the cell has a good energetic level): ATP binds to the enzyme and with this diminishes the affinity for its substrate (with this it makes a sigmoid graph). While the AMP (cell with low energetic level) counteracts the inhibitory activity of ATP.

For the part a)

The molecule 1stAVNGr can function as an activator protein kinase A (PKA), remember that this molecule contains a regulatory subunit and a catalytic subunit. It is necessary that they be together so that they can work and cause a response in the cell. The regulatory subunit must bind to cAMP to activate and bind to the catalytic subunit (which also activates with ATP) once they are joined, a signaling cascade is started which in the end will cause a response in the cell.

For the part b)

For this we must remember that adrenaline (epinephrine) and glucagon are hormones that stimulate glycogenolysis through the membrane proteins known as adenylate cyclase which convert ATP into cAMP directly to indicate to the cell a low energetic level. This is related to the fleeing or fighting response (an evolutionary mechanism). One possible explanation is that the 1stAVNGR molecule works like glucagon or adrenaline joining the receptor (adenylate cyclase) to generate cAMP.

Since we do not know the nature of the 1stAVNGR molecule, if it is non-polar, it can cross the cell membrane and bind to other cAMP-generating enzymes, one of which is adenylate kinase which, from two molecules of ADP, generates an ATP molecule and an AMP molecule.

For the part c)

Remember that G proteins are membrane proteins which are mediated by GTP and these can inhibit or stimulate adenylate cyclase, which would reinforce the previous theory I proposed which says that 1stAVNGR is a non-polar molecule that crosses the membrane and activates other proteins that generate AMP (as adenylate kinase would be)

Related Questions

Navigate

• Browse (All)
• Browse 1
• Subjects

---

---

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