week 4- glycogen degradation

glycogen phosphorylase

sequentially cleaves the alpha-1,4 bonds (can only cleave these bonds) chain ends by simple phosphorolysis (where the glycosidic bond is broken by the addition of a phosphate group), requires vitamin B6 (pyridoxine)

glycogen degradation produces

G1P until 4 glucose units remain before a branch point

branch removal by two enzyme activities of a single bifunctional protein, the debranching enzyme

oligo-alpha (4:4) transferase: removes outer 3 of 4 glucose units of branch and transfers them to non-reducing end (an alpha-1,4 bond broken and one is made); the remaining glucose residue attached in an alpha-1,6 linkage is removed by alpha-1,6 glucosidase activity to free glucose; glycogen phosphorylase can now continue degradation

conversion of G1P to G6P

G1P (produced by glycogen phosphorylase) converted in cytosol by phosphoglucomutase to G6P

fate of G6P is tissue specific- liver

G6P transported to ER by G6P translocase and converted to glucose by G-6-phosphatase, hepatocytes then release glycogen-derived glucose into blood to help maintain blood glucose

fate of G6P is tissue specific- muscle

lacks glucose-6-phosphatase, G6P enter glycolysis to provide energy to contracting muscle

glycogen degradation- kinase

adds phosphate group, converts inactive glycogen phosphorylase to active form

glycogen degradation- phosphatase

removes phosphate group, converts active glycogen phosphorylase to inactive form

regulation of glycogen phosphorylase

glucagon (liver only) or epinephrine (liver, muscle) binding stimulates intracellular cAMP, phosphorylates (activates) glycogen phosphorylase, phosphorylates (inactivates) glycogen synthase, = reciprocal control

when glucagon levels are high (fasting state)

this will cause an increase in the active form of protein kinase A, which will work to ensure that glycogen synthase is inactivated and glycogen phosphorylase is increased to allow breakdown of glycogen stores to glucose as a readily available energy substrate

G6P is an allosteric inhibitor of glycogen phosphorylase

inhibits active glycogen phosphorylase by stimulating its dephosphorylation, more rapid than hormonal regulation

glycogen degradation in skeletal muscle

regulation differs from that of liver in several respects, glucagon has no effect on muscle so glycogen levels in muscle do not vary much with fasting

activation of glycogen phosphorylase during exercise

(1) ATP to ADP to AMP (low energy state) from muscle contraction, (2) calcium release from neutral impulses, (3) epinephrine binding to cAMP