mechanism of glycogen phosphorylase

Question 1

GABC

Answer 1

what we use to break a1-4 glycosidic bond to retain a specific config.

Can do in a few ways:
1. double SN2 OR blocked face SN1 (which is kinetically confirmed)

Question 2

blocked face Sn1

Answer 2

blocked face Sn1, blocking one of the faces so that carbocation can only be attacked from one direction. We know this because it has been kinetically confirmed at random bi-bi mechanism (2 S, 2 P , substrates can add in either order)

Tells you it will be Sn1, if it was Sn2 it would be ping-pong

Question 3

C1’s glycosidic bond

Answer 3

(C1-O)
This bond breaks from the nonreducing end of the glycogen unit meaning we are breaking it off from one of the nonreducing arms…
WHen this bnd breaks, there is a resonance stabilized carbocation because the O e- can form a double bond. No longer have the plus charge at this point, but have positive charge now on the O. (oxonium ion)

This oxonium is in the 1/2 chair, this conf exists because need oxygen and carbocation to be planar in order for you to get the double bond as one of your resonance contribs.

Question 4

Oxonium ion

Answer 4

will ion pair with the mechanistic phosphate, which is H bonded to PLP’s phosphate.

Ion pairing occurs between O- of Pi with the carbocation of oxonium.

Question 5

Lys 568

Answer 5

ion pairing with mechanistic phosphate and PLP’s phosphate.

Question 6

lys 679

Answer 6

schiff base bonded to PLP to have prosthetic group?

Question 7

Mechanism

Answer 7

two way proton exchange/relay…
Typically PLP acts as e- sink. but here the phosphate, is acting as the participant. SO …
e- in glycolytic bond take the proton from PLP Pi2, breaks bond and creates protonated sugar unit with a released glucose unit.

The phosphate then ion pairs with the carbocation.

Retention of config = keeping mechanistic Pi close by so it can only add from below.

Return relay:
e- from PLP
s Pi1 O grabs a proton from Pi2, Pi2 forms ion pair with glucose unit