Glycogenesis

Question 1

Glycogen synthesis

Answer 1

Glucose is activated by attaching UDP from UTP, forming UDP-glucose. This activated glucose is added to glycogen, releasing UDP. To keep the process going, UDP is recycled back into UTP using a phosphate from ATP.

Question 1

Glycogenesis, branching points

Answer 1

In both liver and muscle , 2 ATPs required for the incorporation of a glucose into glycogen chain. G to G6P and UDP to UTP. Branching enzyme needed to introduce alpha 1-6 branch points and limit the size of glycogen molecule (branches become too crowded even if they become progressively shorter, glycogen synthase may need to interact with glycogenin to be fully active).

Question 2

Glycogen branching

Answer 2

Can’t continue to add glucose to glycogen chain. Glycogen branching enzyme cuts some of the chain and joining it to make a branch point.

Question 3

Activation of glycogen synthase

Answer 3

Regulated by reversible phosphorylation. Active when dephosphorylated, inactive when phosphorylated. Dephosphorylation catalysed by protein phosphatase I, phosphorylation catalysed by glycogen synthase kinase. Insulin stimulates PPI and so, causes glycogen synthase to be dephosphorylates and active. So, insulin effectively stimulates glycogen synthase and creates a drive for glycogen synthesis.

Question 4

Glycogenesis in liver

Answer 4

the ‘push’ mechanism. Glycogenesis responds to BGLs without the need of insulin. Although insulin will stimulate glycogen synthase further.

Question 5

Glycogenesis in muscle

Answer 5

[G6P] never get high enough to stimulate glycogen synthase. ‘pull’ method as insulin stimulates GS and drags glucose to glycogen.

Question 6

Importance of glycogenesis

Answer 6

Glucose disposal is done in addition to the background transport facilitated by GLUT-1 and is rapid. Important to do something with the glucose otherwise it exists cell.

Question 7

Glucokinase

Answer 7

Rapidly converts G to G6P. Not inhibited by buildup of G6P. High Km (10mM) for glucose, not saturated by high levels of liver glucose. So, [G6P] increases with [blood glucose]. Only works on glucose, only presents in liver, B cells.

Question 8

G6P can stimulate inactive glycogen synthase

Answer 8

G6P allosterically activates glycogen synthase, even when it’s in its inactive (phosphorylated) form. Glucose (mainly in the liver) promotes the dephosphorylation of glycogen synthase, fully activating it. This regulation involves inhibiting hexokinase and activating protein phosphatases 1

Question 9

Hexokinase

Answer 9

Works on any 6C sugar. Km for glucose ~0.1mM. Strongly inhibited by its product G6P. Present in all other tissues. If G6P is not used immediately, its build up and inhibits HK. Easily saturated with glucose..