Glycogen Synthesis

where is glycogen synthesized

all tissues, but most significantly in liver and muscle

what is glycogen for in liver

storage for use by liver and whole body

what is glycogen for in muscle?

for use by muscle only

notes about glycogen structure

has non-reducing and reducing ends, alpha-1,4 and alpha-1,6 linkages

what is glycogenin

protein bound to glycogen at the reducing end (the C=O terminal)

glycogen phosphorylase function

reacts at non-reducing end (terminal end of glycogen), breaking alpha-1,4 linkages (requires pyridoxal phosphate)

what is the basic enzyme that breaks glycogen

glycogen phosphorylase

debranching enzyme action

works in 3 steps: 1) breaks alpha-1,4 bond several units away from branch, leaving just one glucose branched on adjacent chain, 2) forms a new alpha-1,4 bond, attaching old branch at the end of adjacent chain, 3) releases free glucose, breaking the 1,6 bond

steps of glycogen synthesis

glucose-6-P >>> glucose-1-P >>> UDP-glucose (UTP >>> PPi) >>> glucose(n+1) and UDP

branching enzyme

breaks an alpha 1,4 bond and makes an alpha 1,6 bond

primer for making glycogen

glycogenin

phosphoglucomutase

glucose-6-P >>> glucose-1-P for glycogen synthesis

glycogen synthase is activated by

Dephosphorylation at 3(4) sites

GSK3

Glycogen Synthase Kinase 3 (on glucagon team), It phosphorylates glycogen synthase, inactivating it

regulation of GSK3 (what does insulin do to it?)

insulin inactivates it by phosphorylation by insulin sensitive kinase

PP1

(Phosphoprotein phosphatase) activates glycogen synthase by dephosphorylating it to its active form and inactivates glycogen phosphorylase by dephosphorylation

Ca++ effect on phosphorylase kinase

enhances activity if it's already phosphorylated, activates it if it's not phosphorylated

phosphorylase kinase structure

four subunits, 2 regulatory, 1 catalytic, 1 calmodulin (binds to Calcium and activates or enhances activity)

phosphorylase kinase activity

phosphorylates glycogen phosphorylase b, promoting glycogen breakdown

how is PP1 activated

insulin stimulated kinase phosphorylates GM, activating PP1

Glucagon activity on PP1

phosphorylates GM, causing PP1 to dissociate from complex, stopping dephosphorylation of glycogen phosphorylase and phosphorylase kinase

when GM is phosphorylated

PP1 dissociates and glucagon signal predominates because Glycogen phosphorylase and phosphorylase kinase stay phosphorylated

phosphorylated inhibitor 1

binds to PP1 and inactivates it (PI1 is phosphorylated by PKA, which activates it to inactivate PP1)

activators of PP1

insulin, G6P, glucose (cause increased glycogen synthase activity)

deficiency in branching enzyme

structure of glycogen is abnormal, very long chains form; not compact and not efficient for breakdown

muscle phosphorylase deficiency

muscle can't respond quickly to additional muscle activity

liver phosphorylase deficiency

under starvation, can't break down glycogen

uridine diphosphate glucuronate (UDP-glucuronate)

made from UDP-glucose with 2 NAD+ (makes 2 NADH); important in drug metabolism