PYGL

This gene encodes a homodimeric protein that catalyses the cleavage of alpha-1,4-glucosidic bonds to release glucose-1-phosphate from liver glycogen stores. This protein switches from inactive phosphorylase B to active phosphorylase A by phosphorylation of serine residue 15. Activity of this enzyme is further regulated by multiple allosteric effectors and hormonal controls. Humans have three glycogen phosphorylase genes that encode distinct isozymes that are primarily expressed in liver, brain and muscle, respectively. The liver isozyme serves the glycemic demands of the body in general while the brain and muscle isozymes supply just those tissues. In glycogen storage disease type VI, also known as Hers disease, mutations in liver glycogen phosphorylase inhibit the conversion of glycogen to glucose and results in moderate hypoglycemia, mild ketosis, growth retardation and hepatomegaly. Alternative splicing results in multiple transcript variants encoding different isoforms.

Full Name

liver glycogen phosphorylase

Function

Allosteric enzyme that catalyzes the rate-limiting step in glycogen catabolism, the phosphorolytic cleavage of glycogen to produce glucose-1-phosphate, and plays a central role in maintaining cellular and organismal glucose homeostasis.

Biological Process

Biological Process 5-phosphoribose 1-diphosphate biosynthetic processIEA:Ensembl
Biological Process glucose homeostasisManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process glycogen catabolic processManual Assertion Based On ExperimentIBA:GO_Central
Biological Process glycogen metabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process necroptotic processIEA:Ensembl
Biological Process response to bacteriumIEA:Ensembl

Cellular Location

Cytoplasm, cytosol

Involvement in disease

Glycogen storage disease 6 (GSD6):
A metabolic disorder characterized by mild to moderate hypoglycemia, mild ketosis, growth retardation, and prominent hepatomegaly. Heart and skeletal muscle are not affected.

PTM

Acetylation, which is up-regulated by glucose and insulin and down-regulated by glucagon, inhibits the glycogen phosphorylase activity by promoting PPP1R3B-mediated recruitment of phosphatase PP1 and Ser-15 dephosphorylation.
Phosphorylation at Ser-15 converts inactive phosphorylase b into active phosphorylase a (PubMed:10949035).
Dephosphorylation of Ser-15 by phosphatase PP1 inactivates the enzyme (PubMed:22225877).