Glycogen phosphorylase, liver form (PYGL) (PYGL)

Glycogen phosphorylase, liver form (PYGL) is a key metabolic enzyme that catalyzes the rate-limiting step of glycogenolysis in the liver, converting glycogen into glucose-1-phosphate (Wikipedia, 2024; UniProt, 2024). This process is vital for maintaining blood glucose levels during fasting and is tightly regulated by hormonal and allosteric signals (MedlinePlus, 2024). In type 2 diabetes, the liver often produces excessive glucose, contributing to chronic hyperglycemia, which has led to the investigation of PYGL as a therapeutic target (NIH, 2020). Inhibitors of PYGL are designed to suppress hepatic glucose output and improve glycemic control (PubMed, 2006). However, clinical development has faced hurdles due to safety concerns, as prolonged inhibition can cause significant glycogen accumulation in the liver (AstraZeneca, 2010). This accumulation may lead to hepatomegaly and elevated liver enzymes, similar to the symptoms observed in Hers disease, a genetic condition caused by PYGL deficiency (MedlinePlus, 2024).

Other names

Liver glycogen phosphorylaseHuman liver glycogen phosphorylaseHLGPGSD6Phosphorylase, glycogen, liver

Inhibition of hepatic glycogenolysis by targeting the liver isoform of glycogen phosphorylase to reduce hepatic glucose production and lower systemic blood glucose levels (NIH, 2020; PubMed, 2006).