leverglycogenolyse

Leverglycogenolyse, or hepatic glycogenolysis, is the process by which glycogen stored in the liver is broken down to release glucose or glucose-6-phosphate, helping to maintain blood glucose levels during fasting and stress. In the liver, the released glucose can enter the bloodstream, unlike in skeletal muscle where the glucose-6-phosphate remains inside cells.

Biochemically, leverglycogenolyse begins with glycogen phosphorylase cleaving α-1,4 glycosidic bonds, producing glucose-1-phosphate. Glucose-1-phosphate is converted to glucose-6-phosphate by phosphoglucomutase. At branch points, the debranching enzyme facilitates continued breakdown of glycogen. In hepatocytes, glucose-6-phosphatase then dephosphorylates glucose-6-phosphate to free glucose, which exits the cell through the GLUT2 transporter into the bloodstream.

Regulation of leverglycogenolyse is primarily hormonal. Glucagon (from the pancreas) and epinephrine (adrenal medulla) activate a cAMP-dependent protein kinase A (PKA) pathway that promotes phosphorylation and activation of glycogen phosphorylase, increasing glycogen breakdown. Insulin counteracts this process by reducing cAMP levels and activating protein phosphatase 1, which dephosphorylates and inactivates glycogen phosphorylase. Calcium signaling can also modulate the pathway in some contexts, particularly in the liver during certain hormonal stimuli.

Physiological significance includes maintenance of euglycemia during fasting or early exercise, when hepatic glycogen stores are mobilized to supply glucose to the bloodstream. Defects in hepatic glycogenolysis, such as in Hers disease (glycogen storage disease type VI), can cause hypoglycemia and hepatomegaly due to impaired hepatic glucose release.