ALLOSTERIC:glycogen phosphorylase T to R: AMP vs ATP Flashcards
allosteric
we are discussing the left wall, phosphorylase b.
AMP and ATP
compete for allosteric binding site on b form.
T to R forms
promoted by AMP partly due to alpha phosphate forming ion pairs with arg 309 and 310 in GP. If Arg is present, talking about ion pairs
R to T forms
promoted by ATP’s alpha and b phosphates forming ion pairs with arg310 and arg309 in GP, if have alpha AND beta as opposed to just alpha, will be different set of chemical interactions. WIll have one instead of 2 or two instead of one, depending on how you look at it.
Will also have an additional interaction: ion pairs with the gamma phosphate of ATP. ALL three Pi are forming ion pairs.
a/b are forming ion pair with same arg that just the a/AMP was forming. Plus the gamma is ion pairing additionally.
WHy matters:
ATP strucutre, =have a ribose, and an adenine base. Adenine will move from the spot it was in originally as AMP. NO MORE pi stacking with tyrosine when moving from AMP
folliwng ATP disrupting pi stack with tyr…
the adenine will stick out of the GP, so no more interactions of T to R conformer. Dont have R form interactions, will let T form predominate, because this is the predom form at equilibrium.
muscle phosphorylase b mroe sensitive to…
G6P and AMP than liver phosphorylase b.
liver phosphorylase b is more responsive to
+/- Pi,
How is muscle phosphorylated if there are no glycagon receptors?
- cant phosphorylate with glucagon due to lack of receptors, so can use epinephrine, which can turn on phos control. Muscle can respond to epinephrin.
Muscle GP
G6P will inhbit by competing with AMP. G6P and AMP structurally in common: phosphate and sugar ring (one ribose, one glucose). They will compete due to these similarities.
G6P binding site overlaps AMP, so G6P phosphate ion pairs with argenines in binding site. Sugar position will be different, due to lack of adenine in G6P.
If glucose + g6P are both present.
Right wall: if glucose and G6P present, in a form, will stabilize T state synergistically (together). They are more important in hte liver.