Glycogen Metabolism Overview

Glycogen Metabolism

• The body stores glycogen primarily in the liver and muscle.
• Muscle glycogen provides energy for ATP synthesis during muscle contraction.
• Liver glycogen maintains blood glucose levels, especially during fasting.
• The total glycogen in the body is roughly 400 grams, with 1-2% of the resting muscle weight and about 10% of the well-fed adult liver's fresh weight comprised of glycogen.
• Glycogen is a branched polysaccharide consisting of glucose units.
• Glycogenesis: The synthesis of glycogen from glucose, primarily in the liver. It requires energy (ATP) and specific enzymes.
• A critical enzyme in glycogen synthesis is glycogen synthase.

Glycogenesis

• Glycogen synthase is responsible for forming the a(1→4) glycosidic linkages.
• Branching enzyme (amylo-(1,4 → 1,6)-transglucosidase) creates a(1→6) linkages to branch the glycogen molecule.
• Glycogenesis takes place in the cytosol.

Glycogenolysis

• Glycogenolysis, the breakdown of glycogen, is triggered when needed.
• Glycogen phosphorylase is the enzyme breaking down a(1→4) glycosidic bonds at the non-reducing ends of the glycogen molecule.
• This process produces glucose-1-phosphate.
• A glucosyl residue is removed from each nonreducing end.
• The branching points are removed by two debranching enzymes (a(1→4)-glucan transferase and amylo-a(1→6)-glucosidase) for complete breakdown.

Conversion of Glucose-1-Phosphate

• Glucose-1-phosphate is converted into glucose-6-phosphate by phosphoglucomutase, in the liver or muscles.

Hormonal Regulation

• Glucagon and epinephrine stimulate glycogenolysis & hinder glycogenesis during low blood sugar.
• Insulin triggers glycogenesis & hinders glycogenolysis and keeps blood sugar normal during high blood sugar.
• In muscles, glucagon doesn't have a role in glycogen metabolism.

Glycogen Storage Diseases

• Type I glycogen storage disease is also known as Von Gierke's disease.
• A deficiency in glucose-6-phosphatase causes this disease, leading to excessive glycogen buildup in the liver and difficulty in releasing glucose into the bloodstream.
• This can cause liver enlargement (cirrhosis), and children with this condition often experience early death.
• Treatment consists of frequent small food servings.

Lecture Objectives

• Differentiate between liver and muscle glycogen function.
• Describe glycogenesis and glycogenolysis.
• Explain the hormonal regulation of glycogen metabolism.
• Define the cause of type I and II glycogen storage disease.