Glycogen Metabolism Overview

Glycogen Metabolism

• Glycogen is a storage form of glucose
• Muscles store glycogen for ATP synthesis during contraction
• Liver stores glycogen to maintain blood glucose levels, especially during fasting
• Approximately 400g of glycogen makes up 1-2% of resting muscle weight and 100g makes up to 10% of well-fed adult liver weight
• Glycogen is a branched polysaccharide of glucose, with a-1,4 and a-1,6 glycosidic linkages
• Glycogenesis is the synthesis of glycogen, occurring in the cytosol and needing energy from ATP
• Glycogen synthase makes a-1,4 linkages, and branching enzyme makes a-1,6 linkages
• Glycogenolysis is the breakdown of glycogen, also occurring in the cytosol
• Glycogen phosphorylase cleaves a-1,4 glycosidic bonds at non-reducing ends of glycogen, producing glucose-1-phosphate

Specific Objectives

• Students will be able to differentiate between liver and muscle glycogen function
• Students will be able to discuss the processes of glycogenesis and glycogenolysis
• Students will be able to explain hormonal regulation of glycogen metabolism
• Students will be able to explain the reason for glycogen storage disease type I and II

Structure and Function of Glycogen

• The main stores of glycogen are in skeletal muscle and liver
• Muscle glycogen serves as a fuel reserve for ATP during muscle contraction
• Liver glycogen maintains blood glucose concentration, especially during fasting periods

A. Shortening of Chains (Glycogenolysis)

• Glycogen phosphorylase sequentially cleaves α(1→4) glycosidic bonds at the non-reducing ends of the glycogen chain producing glucose-1-phosphate

B. Removal of Branches

• Branches are removed by a debranching enzyme
• First, a(1→4)-glucan transferase activity removes the outer three glucosyl residues attached at a branch
• Second, amylo-a(1→6)-glucosidase removes glucose at a(1→6) bond
• The glucosyl chain is available again for degradation by glycogen phosphorylase

C. Conversion of Glucose-1-Phosphate to Glucose-6-Phosphate

• This occurs via phosphoglucomutase enzyme in the cytosol

D. Lysosomal Degradation of Glycogen

• A small amount of glycogen (1-3%) is continuously degraded by lysosomal enzyme a(1→4)-glucosidase (acid maltase) in the cytoplasm
• Deficiency of this enzyme leads to glycogen storage disease type II (Pompe disease)

Regulation of Glycogen Synthesis and Degradation

• In the liver, glycogenesis speeds up during well-fed periods, while glycogenolysis speeds up during fasting periods
• In skeletal muscle, glycogenolysis occurs during exercise, followed by glycogenesis when resting

Hormonal Regulation

• Glucagon and epinephrine stimulate glycogen phosphorylase and inhibit glycogen synthase during low blood sugar
• Insulin stimulates glycogen synthase and inhibits glycogen phosphorylase during high blood sugar levels
• Glucagon has no role in muscle

Glycogen Storage Disease Type I

• Also called Von Gierke's disease
• Caused by a deficiency of glucose-6-phosphatase
• Characterized by massive liver enlargement, which can cause cirrhosis
• Children often die in early childhood
• Treatment involves frequent, small food portions