Glycogen Metabolism and Storage Diseases

Glycogen Metabolism

• Glycogen is a storage polysaccharide
• Primarily stored in the liver and muscles
• In muscle, glycogen provides ATP during muscle contraction
• In the liver, glycogen maintains blood glucose levels
• Glycogenesis is the synthesis of glycogen
• Glycogenolysis is the degradation of glycogen
• Glycogen synthesis begins with UDP-glucose
• Glycogen synthase elongates glycogen chains
• Branching enzyme creates branches in glycogen
• Glycogen phosphorylase shortens glycogen chains producing glucose-1-phosphate

Degradation of Glycogen

• Glycogen phosphorylase removes glucose from non-reducing ends, yielding glucose-1-phosphate
• A debranching enzyme removes branches with two enzymatic activities
• A(14)-glucosidase is an example of a lysosomal enzyme
• Defects in glycogen-degrading enzymes cause glycogen storage diseases (GSD)

Glycogen Storage Diseases

• Von Gierke disease (Type Ia): Glucose-6-phosphatase deficiency, fasting hypoglycemia
• GSD Type 1 (b): Glucose-6-phosphate translocase deficiency
• Pompe disease (Type II): Lysosomal a(1,4)-glucosidase deficiency
• Cori disease (Type III): Debranching enzyme deficiency
• McArdle disease (Type V): Skeletal muscle glycogen phosphorylase deficiency
• Hers disease (Type VI): Liver glycogen phosphorylase deficiency

Regulation of Glycogen Synthesis and Degradation

• Glycogen synthase and glycogen phosphorylase are hormonally regulated (phosphorylation/dephosphorylation)
• Allosteric regulation by glucose and energy levels.
• Glucagon (liver) and epinephrine (liver and muscle) stimulate glycogen breakdown, leading to increased cAMP and activation of glycogen phosphorylase.
• Glycogen synthesis occurs when glucose and energy levels are high and insulin stimulates glycogen synthesis via protein phosphatase-1
• Calcium is involved in muscle contraction and glycogen degradation
• AMP also activates glycogen degradation in muscle under extreme conditions like anoxia and ATP depletion.

Allosteric Regulation

• Glycogen synthase and phosphorylase are subject to allosteric regulation, reacting to the cell's energy needs
• High glucose and energy levels promote glycogen synthesis
• Low glucose and energy levels promote glycogen breakdown

Metabolic Characteristics

• Glycogen metabolism occurs primarily in the liver and muscle
• Glycogen synthesis requires UTP and produces UDP-glucose
• Ingestion of glucose increases blood glucose levels, triggering insulin release, promoting glycogen synthesis
• Low blood glucose triggers glucagon release, promoting glycogen degradation

Important Note

• Pompe disease affects all organs containing lysosomes
• Early onset of progressive muscle hypotonia, cardiac failure, death before age 2, is associated with this disease.

This quiz covers important concepts related to glycogen metabolism, including glycogenesis and glycogenolysis. It also discusses glycogen storage diseases, their causes, and symptoms. Test your knowledge of how glycogen functions in the body and the impact of its disorders.