Glykogenphosphorylase

Glykogenphosphorylase, commonly called glycogen phosphorylase, is a cytosolic enzyme that catalyzes the rate-limiting step of glycogenolysis: the phosphorolysis of α-1,4-glycosidic bonds in glycogen to yield glucose-1-phosphate. This reaction uses inorganic phosphate as the phosphate donor and produces a shortened glycogen chain and free glucose-1-phosphate for entry into glycolysis or further metabolism.

In humans, there are three tissue-specific isozymes encoded by separate genes: PYGL (liver), PYGM (muscle), and PYGB (brain). Each isoform shares the same catalytic mechanism but differs in regulation and tissue distribution. The enzyme generally exists as a dimer and is a pyridoxal phosphate (PLP)-dependent enzyme, with the PLP cofactor bound in the active site to facilitate catalysis.

Regulation of glycogen phosphorylase occurs via phosphorylation/dephosphorylation and allosteric control. Phosphorylation by phosphorylase kinase converts the enzyme from the less active phosphorylase b form to the active phosphorylase a form; this phosphorylation is triggered by hormonal signals such as adrenaline and glucagon through the cAMP/PKA pathway. Dephosphorylation by protein phosphatase-1 inactivates the enzyme. Allosteric effectors modulate activity in a tissue-specific manner; AMP activates the muscle enzyme, while glucose allosterically inhibits the liver enzyme, helping to prevent unnecessary glycogen breakdown when glucose is abundant.

Clinical relevance includes glycogen storage diseases caused by deficits in glycogen phosphorylase. McArdle disease (GSD V) results from muscle phosphorylase deficiency, causing exercise intolerance and muscle cramps. Hers disease (GSD VI) arises from liver phosphorylase deficiency, leading to hepatomegaly and hypoglycemia after fasting.

Glycogen phosphorylase thus plays a central role in mobilizing glycogen stores to meet the body’s energy needs.