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Anonymous
06-05-2004, 06:59 PM
Question 3: PFK-1 Regulation in Liver
Given that the phosphofructokinase-1 (PFK-1) enzyme is regulated by insulin, but not via (de)phosphorylation, how is this regulation accomplished?

A. Via increased transcription of the gene encoding this enzyme
B. By recruitment of pre-existing enzyme from the Golgi
C. Via allosteric regulation by fructose-2,6-bisphosphatase
D. Activation by association with IRS-1
E. An inhibitory subunit of the enzyme dissociates after binding cAMP


PFK-1 Regulation by PFK-2 in Liver

http://www.biology.arizona.edu/biochemistry/problem_sets/carbomet/graphics/03t.gif


This regulatory loop is a liver specialty. PFK-2, which exists mainly in liver, is part of a bifunctional enzyme. In the presence of insulin, this activity is activated via dephosphorylation and produces small amounts of fructose-2,6-bisphosphate (note the correspondence between PFK-2 and F-2,6-bisP, vs.the more common enzyme PFK-1 and its product F-1,6-bisP).

Anyway, this small amount of F-2,6-bisP is enough to switch on PFK-1 in liver, leading to eventual conversion of glucose to pyruvate and thence to fatty acids, lipids and other goodies. Again, memorization of this whole scenario can be minimized (but unfortunately not eliminated) by always keeping in mind the purpose of insulin, namely to promote glucose uptake/storage. Or at least you could check yourself by remembering this.



ans:
C. Via allosteric regulation by fructose-2,6-bisphosphatase
Activation of PFK-1 in liver is indirect, and occurs as follows: dephosphorylation of the bifunctional PFK-2/Fructose-bis phosphatase enzyme places this enzyme in the PFK-2 mode, producing fructose-2,3-bisP, which then allosterically activates PFK-1 (the tutorial for this question provides a diagram of this). A bit complicated, but when placed in the context of insulin's role to promote glucose utilization/storage, it fits nicely into the big picture.