Glycogen

Carbohydrate Storage and Synthesis in Liver and Muscle

Glycogenesis and Glycogenolysis

  • Glycogenesis: Process of forming glycogen from glucose for storage.

  • Glycogenolysis: Breakdown of glycogen to release glucose.

Introduction

  • The brain and red blood cells (RBCs) have an absolute requirement for blood glucose.

  • Between meals, the liver serves as a key source of glucose from glycogen.

    • Liver Glycogen: Approximately a 3-hour supply for blood glucose needs.

    • Liver Gluconeogenesis: The process of producing glucose from non-carbohydrate sources.

Source of Blood Glucose During a Normal Day

  • Dietary sources, gluconeogenesis, and glycogenolysis contribute to blood glucose levels.

  • Graphical representation shows glucose sources around meals (Breakfast, Lunch, Dinner).

Glucose and Glycogen Stores in the Body (for a 70 kg Adult)

  • Tissue: Amount of glycogen and glucose in various tissues.

    • Liver:

      • Type: Glycogen

      • Amount: 75g (3-5% of liver mass)

      • Calories: 300 kcal

    • Muscle:

      • Type: Glycogen

      • Amount: 250g (0.5-1.0% of muscle mass)

      • Calories: 1000 kcal

    • Blood:

      • Glucose: 10g, Calories: 40 kcal.

Structure of Glycogen

  • Glycogen is composed of alpha-1,4 and alpha-1,6 linkages.

    • It has a branched structure that facilitates rapid digestion and energy release.

Entrance of Glucose into the Liver

  1. Glucose Transport: Enters via the Glut-2 transporter, which is freely permeable to glucose.

  2. Role of Glucokinase: Converts glucose to glucose-6-phosphate (G6P).

    • Inducible with increased activity after high carbohydrate meals.

  3. Replenishment of Glycogen: Prepares glycogen storage followed by glycolysis and triglyceride synthesis.

Glycogenesis Pathway

  • Core Steps:

    1. Glucose enters liver through Glut-2 transporter.

    2. Glycogen synthase adds glucose molecules to form glycogen.

    3. Branching occurs via branching enzyme, creating more accessible glucose storage.

Enzymes in Glycogenesis

  • Hexokinase (Glucokinase): Converts glucose to glucose-6-phosphate.

  • Phosphoglucomutase: Converts G6P to glucose-1-phosphate.

  • UDP Glucose Phosphorylase: Converts glucose-1-phosphate to UDP-glucose.

  • Glycogenin: Serves as a primer in glycogen synthesis.

  • Glycogen Synthase: Main enzyme in glycogen synthesis.

  • Branching Enzyme: Responsible for creating branches in glycogen.

Hormonal Regulation of Glycogenesis

  • Insulin Effects:

    • Activates glycogen synthase.

    • Inhibits glycogen phosphorylase.

    • Stimulates glucose uptake in muscle and adipose tissue.

    • Induces gene expression for enzymes, enhancing Glut-4 transporter activity.

  • Glucagon Effects: Opposes insulin’s action to increase blood glucose.

Glycogenolysis

  • Pathway Overview:

    1. Glucose leaves the liver via the Glut-2 transporter.

    2. The enzyme glucose-6-phosphatase is crucial for glucose export and exists only in the liver.

Enzymes in Glycogenolysis

  • Glycogen Phosphorylase: Catalyzes the breakdown of glycogen into glucose-1-phosphate.

    • Specific for alpha-1,4 bonds.

  • Debranching Enzyme: Needed for processing alpha-1,6 linkages, allowing glycogen phosphorylase to continue activity.

Hormonal Control of Glycogenolysis

  • Hormones regulating glycogenolysis include:

    • Glucagon: Stimulates glycogenolysis during hypoglycemic states.

    • Epinephrine: Activates glycogenolysis as a response to stress, hypoglycemia, and during exercise.

    • Cortisol: Contributes to chronic activation of glycogenolysis.

    • Insulin: Promotes inactivation of glycogenolysis during hyperglycemia.

Mechanism of Epinephrine Action on Glycogenolysis

  • Epinephrine binds to beta adrenergic receptors, activating a cascade that increases phosphorylase kinase.

  • This leads to the activation of glycogen phosphorylase, facilitating glycogen breakdown.

Stress Response and Glycogen Breakdown

  • During prolonged exercise or stress, epinephrine stimulates rapid glycogenolysis, ensuring a continuous glucose supply.

Calcium Ion Influence on Glycogenolysis

-Calcium-Calmodulin Complex: Activates glycogen phosphorylase kinase, promoting glycogen breakdown independent of hormonal signals.

  • High AMP levels also activate phosphorylase kinase and relieve inhibition on PFK-1, promoting glycolysis.

Summary of Glycogen Regulation

  • Glycogen Phosphorylase: Exists in inactive (b) and active (a) forms. Activation leads to glycogen breakdown, while phosphorylation inactivates it.

  • Insulin promotes the dephosphorylation and activation of glycogen synthase, balancing glycogen synthesis and breakdown.