Research in cell biology and metabolism has progressed due to the discovery of molecules that artificially...

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Biology

Research in cell biology and metabolism has progressed due tothe discovery of molecules that artificially stimulate or inhibitglucagon/epinephrine and insulin signaling pathways. Let’s say youare working in a lab cataloging the effects of a library of smallmolecules on these pathways and have a “hit” on molecule 1stAVNGR.Preliminary data on molecule 1stAVNGR indicates that the cardiacisoform of PFK2/FBPase2 is doubly phosphorylated when this moleculeis present at micromolar concentrations in cell cultures. Giventhis context answer the following questions.

a. Under these conditions what is the predicted degree ofassociation between the regulatory subunits and the catalyticsubunits of PKA?

b. Further investigation of molecule 1stAVNGR indicates elevatedlevels of cAMP within the cell despite the absence of epinephrineor glucagon. Hypothesize two possible explanations for thisdata.

c. When cell cultures are given both molecule 1stAVNGR andmolecule RedSKLL (a G-protein inhibitor) cAMP levels remain high(again despite the absence of epinephrine or glucagon). Given thisnew information hypothesize a possible explanation for thedata.

d. In consideration of the data presented in this problem whatwould be the expected effect of molecule 1stAVNGR on glycolyticflux in a culture of cardiac myocytes? Explain your reasoning?

e. Finally, if molecule 1stAVNGR were infused into a culture ofhepatocytes what would be the expected effect on glycolytic flux inthese cells? Explain your reasoning.

Answer & Explanation Solved by verified expert
3.6 Ratings (358 Votes)
a Bifunctional enzyme 6phosphofructo2kinase PFK2fructose26 bisphosphatase FBPase2 controls the level of fructose26 bisphosphate in the cardiac cells This enzyme has 100 times more PFK2 activity than FBase2 PFK2 leads to production of fructose 26 bisphosphate while Fbase2 degrades it In heart PFK2 is activated by protein kinase A PKA Inactive PKA is composed of two dimeric regulatory R subunits forming a dimer and two catalytic C subunits The catalytic subunits are bound to the R subunits to form the inactive tetrameric holoenzyme Activation of PKA occurs due to an increase in intracellular cAMP concentration During activation two cAMP molecules bind to each R subunit As a    See Answer
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