Glycogen biosynthesis (UDP-glucose → glycogen) — GSD 0/IV/XV, UGP2-DEE

Glycogen biosynthesis is the cytosolic pathway that builds the branched glucose polymer glycogen from the activated sugar donor UDP-glucose, storing glucose for later mobilisation. Four steps: UDP-glucose pyrophosphorylase (UGP2) activates glucose-1-phosphate with UTP to form UDP-glucose + pyrophosphate; glycogenin (GYG1) primes synthesis by autoglucosylating a specific tyrosine, using UDP-glucose to build a short covalently-attached alpha-1,4-glucan (~8-12 residues) that nucleates the granule; glycogen synthase (muscle GYS1, liver GYS2) then elongates the chain by processively adding UDP-glucose-derived glucose units in alpha-1,4 linkage; and the glycogen branching enzyme (GBE1) transfers ~6-7-residue segments to internal positions via alpha-1,6 linkages, creating the branches that make glycogen soluble and multiply the non-reducing ends for both synthesis and later degradation. Glycogen synthase is the rate-controlling, tightly regulated step (inhibited by phosphorylation, allosterically activated by glucose-6-phosphate). Inherited defects define disorders across the pathway: UGP2 deficiency causes a developmental and epileptic encephalopathy; GYG1 deficiency causes glycogen storage disease type XV (polyglucosan-body myopathy/cardiomyopathy); GYS2 deficiency causes hepatic glycogen storage disease type 0a (fasting ketotic hypoglycemia) and GYS1 deficiency muscle GSD 0b (cardiomyopathy, sudden death); and GBE1 deficiency causes GSD type IV (Andersen disease) and adult polyglucosan body disease — accumulation of poorly branched, amylopectin-like polyglucosan.