PYGL Human

The gene encoding the liver form of glycogen phosphorylase is located on chromosome 14q22.1 . The protein consists of 847 amino acids and is allosterically regulated, meaning its activity is controlled by the binding of metabolites and post-translational modifications . The enzyme is activated by AMP and inhibited by ATP, ADP, and glucose-6-phosphate .

Glycogen phosphorylase catalyzes the rate-limiting step in glycogenolysis, the process of breaking down glycogen into glucose-1-phosphate . This reaction is essential for providing glucose during periods of fasting, exercise, and stress. The enzyme’s activity is regulated by the interconversion between its active phosphorylated form and its inactive non-phosphorylated form .

Mutations in the PYGL gene can lead to Glycogen Storage Disease Type VI (GSD VI), also known as Hers disease . This autosomal recessive disorder is characterized by the inability to properly break down glycogen, leading to its accumulation in the liver and resulting in hepatomegaly, growth retardation, and mild hypoglycemia .

The recombinant form of human liver glycogen phosphorylase is produced using genetic engineering techniques. This involves cloning the PYGL gene into an expression vector, which is then introduced into a host cell, such as E. coli or insect cells, to produce the recombinant protein . The recombinant enzyme is used in research to study its structure, function, and regulation, as well as to develop potential therapies for glycogen storage diseases.

Research on recombinant human liver glycogen phosphorylase has provided valuable insights into its regulatory mechanisms and its role in glucose metabolism . Studies have shown that glucose is a major regulator of the enzyme’s activity, with changes in glucose concentration significantly affecting its function . This knowledge is crucial for understanding metabolic disorders and developing targeted treatments.