Glycogenolysis
Stored glucose back out, one phosphorolysis at a time.
~90% as G1P at zero ATP cost · ~10% free glucose from branch points
This mnemonic, unpacked word by word →
The mirror image of glycogenesis, run by one amplification cascade: PKA switches glycogen synthase OFF directly and phosphorylase ON through phosphorylase kinase, so the two pathways can never run at once. Liver breaks glycogen down for the blood; muscle keeps every glucose for itself.
The amplification cascade: one hormone at a GPCR → adenylyl cyclase → cAMP → PKA → phosphorylase kinase → phosphorylase, each tier multiplying the signal (GLUCaGON: released when GLUCose is GONe). The tongue-twister is the mnemonic: protein kinase phosphorylates phosphorylase kinase, which phosphorylates phosphorylase. In muscle, Ca²⁺ from contraction (via the calmodulin subunit of phosphorylase kinase) and AMP activate phosphorylase with no hormone at all, so exercise mobilizes glycogen directly.
Rate-limiting. Cleaved by phosphorolysis, where inorganic phosphate rather than water attacks the α-1,4 bond, so glucose comes off pre-phosphorylated at zero ATP cost. Requires pyridoxal phosphate (B6). Activated by glucagon, epinephrine, AMP; inhibited by insulin, ATP and G6P. Stops four residues short of every branch. Muscle isoform missing in McArdle (GSD V), liver isoform in Hers (GSD VI).
Two activities in one protein: a transferase moves three of the last four residues onto the main chain, then α-1,6-glucosidase hydrolyzes the branch-point residue, releasing the only free, unphosphorylated glucose glycogen ever yields. Deficiency is Cori disease (GSD III): like a milder Von Gierke, but gluconeogenesis is intact so lactate stays normal.
The fork in the road: muscle sends G6P straight into glycolysis and keeps the fuel. Only the liver takes the final step.
The same enzyme that finishes gluconeogenesis, in liver and kidney only, which is why muscle glycogen is selfish. Missing in Von Gierke disease (GSD I): fasting hypoglycemia, big liver, and no glucose response to glucagon.