main sites of synthesis:

Liver [8%]

muscle [1%]

since most people have more muscle than liver, there is more glycogen stored in the muscle than liver

dynamic source

synthesizes and stores glycogen after a carb meal

degrades glycogen to free glucose during fasting

stable source

synthesizes glycogen at rest

degrades glycogen during exercise to gereate quick ATP

many nonreducing ends [10 to 40,000 glucose residues]

1 reducing end

anomeric carbon [exposing aldehyde or ketone]

glycogenin core

alpha 1,4 linkages

alpha 1,6 linkages every 10 to 12 residues

MW=10⁶ to 10⁷ 

isomerize glucose 6-phosphate to glucose-1-phosphate

phosphoglucomutase

G1P activation

uridine diphosphate synthesis

driving force: hydrolysis of pyrophosphate

UTP used, 2 Pi come off

alpha 1,4 bond

UDP-glucose = 7.3 kcal/mol

glycogen = 4.5 kcal/mol

UDP at C1 [anomeric] tranferred to C4 hydroxyl group at nonreducing end of the glycogen chain

alpha 1,6 bond

transfers 7 unbranched residues to a C6 ≥4 residues from previous alpha 1,6 branch point

[image]

2 phosphoanhydride bonds/glucose

1ATP for glucokinase/hexokinase

1UTP to make UDP-glucose

regulated step

cleaves alpha 1,4 bond

uses Pi to cleave at nonreducing ends

product is G1P [92% yield]

reversible but Pi/G1P > 100 so it only degrades

stops 4 residues before branch point

requires pyridoxal phosphate

transglycosylase: transfers a block of 3 G residues to the C4 end; cannot cleave alpha 1,6

glucosidase: cleaves the alpha 1,6 bond at the branch point, releasing 1 glucose [yield 8%]

glycogen degrades to yield G1P and glucose when fasting

after isomerization of G1P [by phosphoglucomutase], G6P is dephosphorylated by G6Pase and enters blood

[image]

G6P generated goes into glycolysis and generates 3ATP/glucose

skeletal muscle does not have G6Pase so glucose cannot leave the cell

degradation of glycogen is glucose sparing

reduces phosphorylation of regulated enzymes

stimulates glycogen synthesis

induces phosphorylation of regulated enzymes

stimulates glycogen degradation in the liver

released from pancreatic beta cells [glucose stimulated]

reduces cAMP levels [through phosphodiesterase]

inhibits glycogen synthase kinase-3 [GSK-3]

stimulates protein phosphatase-1

in the liver:

insulin reduces cAMP and inhibits GSK-3 preventing phosphorylation of GS

insulin stimulates PP1 to dephosphorylate GS

in muscle:

G6P stimulates GS

phosphorylates: through covalent modification and allosteric effectors

1. inactivates GS

2. activates glycogen phosphorylase [phosphorylase kinase]

3. activates PP1 inhibitor and that binds to PP1

causes release of G1P

only in liver metabolism, not muscle

[image]

[image]

liver isoform is inhibited by glucose and is phosphorylated through glucagon or epinephrine

[image]

glycogen phosphorylase b is allosterically regulated by AMP and inhibited by G6P

epinephrine stimulates GP to generate G6P to use in glycolysis for quick energy

[image]

phosphorylation stimulates glycogen degradation

dephosphorylation stimulates glycogen synthesis

different:

receptors

enzyme isoforms

enzyme expression

[image]

x linked phosphorylase kinase deficiency

rare [1/40,000] autosomal recessive

deficiency is usually tissue specific due to isozymes

defective glycogen degrading enzymes

accumulation of liver and/or muscle glycogen

fasting hypoglycemia

cori's disease: alpha 1,6 glycosidase

hers' disease: glycogen phosphorylase or phosphorylase kinase

von Gierke's disease: G6Pase

McArdel's disease: muscle glycogen phosphorylase

Tarui disease: PFK1 [glycolysis is slow and G6P can't leave the cell]

Pompe disease: lysosomal alpha 1,4 glucosidase and alpha 1,6 glucosidase [aka acid maltase or alpha glucosidase]

mutation in gene that makes acid alpha glucosidase