Glycogen synthesis (glycogenesis): G6P → G1P (phosphoglucomutase) → UDP-glucose (UDP-glucose pyrophosphorylase) → glycogen extension by glycogen synthase. Glycogen breakdown (glycogenolysis): glycogen phosphorylase → G1P → G6P → fates. Liver glycogen feeds blood glucose; muscle glycogen feeds local glycolysis only (no G6Pase). Glycogen storage diseases: von Gierke (G6Pase, type I), Pompe (acid maltase, type II — only one affecting lysosomal glycogen), McArdle (muscle phosphorylase, type V). Regulation: glucagon + epinephrine activate phosphorylase via PKA cascade; insulin activates glycogen synthase via PP1.
Organ Systems
endocrine
musculoskeletal
digestive
Pathway Steps
glucose-6-phosphate → glucose-1-phosphate — via phosphoglucomutase. Phosphoglucomutase reversibly interconverts G6P and G1P — the hub that links glycogen to glycolysis (via G6P) and to nucleotide-sugar synthesis. Direction follows whether the cell is storing or mobilizing glycogen.
glucose-1-phosphate → udp-glucose — via UDP-glucose pyrophosphorylase. UDP-glucose pyrophosphorylase activates G1P to UDP-glucose at the cost of UTP; hydrolysis of the released pyrophosphate pulls the reaction forward. UDP-glucose is the universal glucosyl donor — for glycogen and for glucuronidation.
udp-glucose → glycogen — via glycogen synthase (insulin-activated). Glycogen synthase is the rate-limiting synthetic enzyme, extending α-1,4 chains (branching enzyme adds α-1,6 branches). Insulin activates it via PP1 dephosphorylation and G6P activates it allosterically, while PKA phosphorylation inhibits it — reciprocal with phosphorylase.
glycogen → glucose-1-phosphate — via glycogen phosphorylase (glucagon/epinephrine-activated via PKA). Glycogen phosphorylase releases G1P by phosphorolysis and is the rate-limiting breakdown enzyme — activated by glucagon/epinephrine (PKA cascade) and, in muscle, by AMP and Ca²⁺. Myophosphorylase deficiency is McArdle disease (exercise intolerance); liver and muscle isoforms differ.