3. Glucose uptake and storage 3_2024_MPAL_

Glucose Uptake and Storage

Major Pathways of Glucose Metabolism

What is Glycogen?

Structure of Glycogen

  • Glycogen is a multi-branched polysaccharide that serves as a form of energy storage in animals.

  • It consists of glucose units linked together.

Function of Glycogen Storage

Why Cells Store Glucose as a Polymer

  • Osmotic pressure is impacted by the concentration of glucose in a cell.

  • Glycogen can represent up to 10% of liver wet weight, which corresponds to a high concentration of free glucose.

  • Maintaining glucose in polymer form limits the osmotic pressure, preventing liver cell swelling and bursting.

  • By linking glucose units, the osmotic effect is diluted, allowing efficient storage without damaging cellular integrity.

Overview of Glycogen Metabolism

Key Enzymes and Pathways

  • Main Enzymatic Players:

    • Glycogen branching enzyme

    • Glycogen synthase

    • Glycogen phosphorylase

    • Inorganic pyrophosphatase

    • Phosphoglucomutase

Glycogen Synthesis

Role of Glycogenin and Branching Enzymes

  • Glycogenin is essential for initiating glycogen synthesis.

  • UDP-glucose acts to elongate glycogen chains through glycogen synthase, promoting a branched structure through the action of branching enzymes.

Glycogen Degradation

  • Glycogen breakdown is facilitated by glycogen phosphorylase and involves debranching enzymes to fully mobilize glucose-1-phosphate for energy use.

Regulation of Glycogen Metabolism

Allosteric Regulation

  • High levels of glucose promote glycogen synthase activity, while low glucose levels activate glycogen phosphorylase.

Hormonal Control

  • Key hormones influencing glycogen metabolism: Epinephrine, Glucagon, and Insulin.

  • These hormones trigger pathways that affect glycogen synthesis and breakdown, mediated through secondary messengers like cAMP.

Phosphorylase Regulation in Liver & Muscle

Glycogen Storage Diseases

Overview

  • Glycogen storage diseases are inherited disorders due to defective enzymes involved in glycogen metabolism.

  • Enzyme deficiency results in abnormal glycogen accumulation, impairing liver and muscle function.

Important Types of Glycogen Storage Diseases

  • Type 0 (Glycogen Synthase Deficiency): Low blood glucose; early death.

  • Type Ia (von Gierke): Enlarged liver; kidney failure due to a lack of glucose-6-phosphatase.

  • Type II (Pompe): Muscle and heart-related issues due to deficiency of glucosidase.

  • Type III (Cori or Forbes): Debranching enzyme deficiency causing liver and muscle problems.

  • Type V (McArdle): Skeletal muscle phosphorylase deficiency; exercise-induced cramps and myoglobinuria.

Summary of Type Ia (von Gierke) Disease

  • Characterized by defect in glucose-6-phosphatase, leading to significant accumulation of glycogen.

  • Symptoms include profound liver enlargement, hypoglycemia, and metabolic derangements, including increased lactate levels.

Glucose Transport and Homeostasis

  • Glucose-6-phosphate's dephosphorylation in the ER allows effective transport and regulation of glucose homeostasis.

Muscle and Liver Collaboration

  • In exercise, skeletal muscle can convert lactate back to glucose in the liver, demonstrating the interconnectedness of metabolic pathways across tissues.

Learning Outcomes Recap

  • Reinforced understanding of glycogen structure, regulation, glycogen storage diseases, and their implications on metabolic health.