Chapter 24

Chapter 24: Glycogen Degradation Overview

  • Focuses on:

    • Glycogen-degrading enzymes.

    • Regulation of glycogen phosphorylase.

    • Role of intercellular signaling in glycogen breakdown.

Key Concepts in Glycogen Degradation

  • Glycogen synthesis and degradation are co-regulated with glycolysis and gluconeogenesis (see Chapters 16 and 17).

Glycogen Structure

  • Glycogen is a polymer of glucose, functioning as an energy storage molecule in animal cells.

    • Rapid mobilization of glucose for energy occurs mainly in the absence of oxygen, supporting brain and red blood cells.

  • Structure features:

    • Glycogen granule nucleated by glycogenin (dimeric protein).

    • Branches occur approximately every twelve residues.

    • Muscles contain about 2% glycogen by weight (for movement) while the liver harbors around 10% (for sustaining blood-glucose levels).

    • Major reactions occur at non-reducing ends of glucose chains.

Glycogen Degradation Enzymes

  1. Glycogen Phosphorylase: Key enzyme that cleaves glycogen chains.

    • Converts glycogen into glucose 1-phosphate through phosphorolysis rather than hydrolysis, requiring Pi.

    • Phosphate addition activates the product, preventing ATP usage and retaining glucose within the cell.

  2. Additional Enzymes Needed for Branch Points:

    • Transferase: Moves glucose residues from one branch to another.

    • α-1,6-Glucosidase (Debranching Enzyme): Hydrolyzes 1,6 linkages, allowing full glucose extraction.

    • Hexokinase: Phosphorylates released glucose from debranching.

    • Phosphoglucomutase: Converts glucose 1-phosphate to glucose 6-phosphate for glycolytic entry.

Disease Associated with Glycogen Breakdown

  • Failures in debranching enzymes can lead to genetic diseases.

  • Hers Disease: A hereditary disorder due to mutations in the liver isozyme of glycogen phosphorylase, causing liver enlargement and low blood glucose levels.

Regulation of Glycogen Phosphorylase

  • Types of Phosphorylase:

    • Phosphorylase a: Active, phosphorylated form.

    • Phosphorylase b: Inactive, non-phosphorylated form.

  • Conformation states:

    • R State (Relaxed): More active.

    • T State (Tense): Less active and partially blocked.

  • Tissue-Specific Regulation:

    • Muscle: B form predominant at rest, activated during exercise.

    • Liver: A form is typically active, modulated by glucose levels.

Allosteric Regulation in Muscle and Liver

  • Muscle:

    • Energy charge modulates activity: High ATP/Glucose 6-Phosphate stabilizes T state (inhibitory).

    • Low ATP/High AMP activates phosphorylase (R state).

  • Liver:

    • Active unless free glucose is present.

    • Hormonal control via insulin (dephosphorylation) and glucagon (phosphorylation).

Hormonal Regulation

  • Epinephrine: Stimulates glycogen breakdown in muscles and liver during activity.

  • Glucagon: Signals low glucose levels, promotes breakdown in the liver.

  • Both hormones regulate phosphorylase via G-protein linked signaling pathways.

Summary of Key Enzymatic Activities in Glycogen Degradation

  • Six crucial enzymes:

    • Glycogen Phosphorylase: Initial cleavage.

    • Transferase: Moves branches.

    • Debranching Enzyme: Completes degradation.

    • Hexokinase: Phosphorylates glucose.

    • Phosphoglucomutase: Converts glucose 1-P to glucose 6-P.

    • Glucose 6-Phosphatase: Exclusively in the liver for glucose export.

Key Concept Questions

  • Glycogen structure, glycosidic bonds, and enzymatic actions involved in degradation are essential for understanding glucose metabolism.