glycogen synthesis and glycogenin Flashcards
Problems
cant find any physiology concentration of Pi to thermodynamically add in a favorable sense G1P to glycogen.
Second problem is that GS needs a primer, cannot start with nothing and build a chain, needs a prebuilt piece of a chain. GS will add units to an existing glycogen chain, when that chain as 10 units of sugar added. So NEED a 10 unit sugar before we can do anything.
initiation and initail extension
glycogenin.
glycogenin
homodimer, has an active site in both SU, in both cases there is a tyrosine that is important.
what is this rxn
auto catalytic rxn, catalysizing on itself. So can build the chain from scratch, leave, and pass it on to GS
on the first glucose unit
glycogenin will attach 1st glucose unit to the special tyrosine in the AS of glycogenin. So for the first UDP glucose, the tyrosine is the acceptor of the 1st UDPG unit.
Before we can attachh tehe glucose, need to do a few things:
Need to remove proton from tyrosine (Or else there will be O+ which we dont want)
Need to attach an Asp from enzyme to C1 of glucose temporarily. Two separate aspartates.
Asp attacking 1st UDPG mech
Asp 162 does attack to displace UDP, which will give u the first SN2 which has Asp 162 attached to sugar unit.
to have Tyr oxygen attack glucose, need to remove proton on tyrosine, which involves GABC with Asp 159. This is second SN2/
DOUBLE SN2
Remaining rxns
required to have alpha 1-4, bc this is what links sugar units together. Anomeric C of the sugars you are adding will add to the C4 OH of the previous glucose after temporary bond with asp 162, this is double inversion so double SN2.
So for the second UDP glucose and everything beyond, the acceptor is the C4 OH of the previous glucose.
end terminal porton of glycogenin
rossmann fold, the nucleotide/deriv is the UDP glucose
need Mn2+ or Mg2+. why
need it there to be a charge soak for the phosphates in this rxn
