Lecture 21 - Glycobiology 2 Flashcards
How is glycogen structured
α(14) linked glucose
α(16) linked branch points
Polydisperse (no one structure) and precise structures vary from molecule to molecule
Inner region - B chains - 2 branch points
Outer region - A chains, unbranched
SLIDE 3 + 4
What is glycogenin
SLIDE 4 and 6
How many glucoses are found in a typical glycogen in vivo
1500 glucose - ~130 outer chains
(theoretical maximum of ~55000)
What happens when glycogen grows and 13 residues have been added
The branching enzyme recognises the target and makes a new branch and the new chain is grown
Why are outer chains unbranched
Makes the glucose easily accessible
Outermost tier always contains 34.6% of the glucose of the glycogen molecule
What is the primer for formation of glycogen
glycogenin
(protein homodimer found at the core of a glycogen molecule)
What are proteins associated with each glycogen molecule responsible for
Synthesis and breakdown (control)
In glycogenin, what is the first glucose added to (in humans)
Tyrosine position 195
(Tyr195)
(self catalysing)
At what point does glycogen synthase take over the catalysing of glucose addition from glycogenin
10-20 residues
What is the energy source to add glucose to glycogen
Glycogenin and glycogen synthase utilise activated precursors
UDP-glucose – in eukaryotes
(ADP-glucose used in bacteria and plants [starch])
UTP + glucose-1-phosphate
—-> UDP-glucose
What is the conversion of UTP+glucose-1-phosphate ——> UDP-Glucose catalysed by
UDP-glucose pyrophosphorylase
Slide 17
What type of reaction is the UDP-glucose addition
Glycosyl transfer with release of UDP
What are the 2 mechanism theories in synthesis of UDP
Double SN2
SNi
How does branching reactions occur
Branching enzyme – amylo-(1,4 1,6)transglycosylase
A terminal chain section of ~7 residues is transferred to the C6-OH of another glycogen chain
What are the enzymes involved in degradation of glycogen
Glycogen phosphorylase
Glycogen debranching enzyme
Phosphoglucomutase
What is the benefit of having separate cycles of degradation and synthesis
Allows fine regulation of glucose release
What does glycogen phosphorylase mitigation
Can only get to within 5 residues of a branch point
What is the glycogen phosphorylase mechanism
- via a carbocation (SN1)
Carbocation is stabilised by pyridoxal phosphate which is covalently linked to the enzyme (PLP is active form of Vit B6)
What is the bi functions of the debranching enzyme
transferase and alpha-1,6 glucosidase
What does phosphoglucomutase do
Converts G-1-P into G-6-P
G-6-P enters glycolysis or in liver it is dephosphorylated to form glucose for the blood
What occurs when glucose is plentiful
G-6-P is formed by hexokinaseChanges equilibrium positionPhosphoglucomutase converts G-6-P in to G-1-PG-1-P is substrate to form UDP-glucose for glycogen synthesis
What is the degradative and synthetic ratio in the liver
Equal
What is the ratio of degradation to synthesis in muscle
300 times faster
