Glycogen Synthesis and Breakdown p1 wk3

Introduction to Glycogen Synthesis and Breakdown

  • The lecture focuses on glycogen, the process of glycogen synthesis, and breakdown, acknowledging the territory of the Kaggle land and the importance of the elders past, present, and emerging.

Summary of Glycogen

  • Glycogen is the polymeric form of glucose, serving as a storage form when there is excess glucose in the cells.

    • Pathways for glycogen synthesis and breakdown are tightly regulated.

    • The lecture’s learning outcomes include:

    • Understanding the process of glycogen synthesis from glucose.

    • Exploring how glycogen is broken down for energy.

    • Learning about the regulation of both processes.

    • Engaging in problem-solving to test understanding of glycogen metabolism.

    • Reference for the lecture: Leningen Principles of Biochemistry, Chapter 15.

Historical Context of Glycogen

  • Glycogen was first discovered in the 1800s by Claude Bernhardt, a French physiologist.

    • He identified an enzyme in the liver that released reducing sugar, naming it glycogen because of its sugar-forming properties.

Structure of Glycogen

  • Glycogen comprises branched chains of glucose molecules, connected by linkages:

    • Alpha-1,4 glycosidic bond: Links linear glucose molecules.

    • Alpha-1,6 glycosidic bond: Forms branches in glycogen structure.

    • Glycogen is primarily stored in the liver and muscles.

    • A 70 kg male can store approximately 480 grams of glycogen.

    • This glycogen can be broken down to release glucose for glycolysis to produce ATP when energy is needed.

    • Glycogen appears as granules in the cytosol of cells.

Energy from Food Sources

  • Energy intake and storage are discussed with respect to a 70 kg male consuming an average of 2000 kcal/day.

    • Breakdown of different substrates yields various amounts of energy:

    • Glycogen (carbohydrates): 4 kcal/g.

    • Proteins: 4 kcal/g, with approximately 6000 g stored.

    • Fats: 9 kcal/g, with an estimated 12000 g stored.

    • Energy calculations demonstrate how long energy stores can last without food intake:

    • Glycogen: 480 g x 4 kcal/g = 1920 kcal, which can sustain energy for 1 day.

    • Protein: 6000 g x 4 = 24000 kcal, lasting for 12 days.

    • Fats: 12000 g x 9 = 108000 kcal, lasting for approximately 54 days.

    • Important note on the impracticality of relying solely on fats for energy.

Key Definitions

  • Non-reducing Sugar:

    • A sugar that does not possess a free aldehyde or ketone as a functional group and does not undergo oxidation.

  • Non-reducing End of Glycogen:

    • The end of a glycogen chain from which glucose units are removed during glycogenolysis (the breakdown process).

Glycogen Synthesis Mechanism

  • Glycogen synthesis begins with a dimer known as glycogenin, which serves as a primer.

    • Glycogenin is a dimer (two subunits), where the synthesis begins.

  • The structure contains several tiers of chains (A chains as outermost, B chains as inner):

    • Maximum of 12 tiers of branching in mature glycogen granules.

    • The general mechanism of glycogen storage and mobilization is similar in liver and muscle tissues but differs in enzyme functionality reflecting each tissue’s role.

Enzymes in Glycogen Metabolism

  • Glycogen Synthase:

    • A key enzyme in synthesizing glycogen from glucose.

    • Cannot initiate new glycogen chains without a primer (glycogenin).

    • Tightly regulated due to its central role in glycogen synthesis.

  • Glycogen Phosphorylase:

    • Enzyme responsible for breaking down glycogen.

Steps of Glycogen Synthesis

  1. Formation of Glycogen Core:

    • A glucose molecule is transferred from UDP-glucose to a tyrosine residue (position 194) on glycogenin, catalyzed by glucosyltransferase.

    • Subsequent glucose molecules are added through similar reactions, forming a small chain attached to the glycogenin dimer.

  2. Role of Glycogen Synthase:

    • After a short chain is formed, glycogen synthase takes over to extend the chain (using alpha-1,4 linkages) and to initiate branching (using alpha-1,6 linkages).

  3. Conversion Process:

    • Glucose-6-phosphate (substrate from glycolysis) converts to glucose-1-phosphate through the enzyme phosphoglucomutase, which facilitates the transfer of a phosphate between carbon 6 and carbon 1.

    • Glucose-1-phosphate reacts with uridine triphosphate (UTP) via UDP-glucopyrophosphorylase to yield UDP-glucose and pyrophosphate (PPi).

    • UDP-glucose is utilized by glycogen synthase to add glucose molecules to the growing glycogen chain, forming the alpha-1,4 and alpha-1,6 glycosidic linkages.

Conclusion

  • The first video concluded with an overview of glycogen synthesis.

  • Next, the focus will shift to glycogen breakdown, particularly when cells signal energy need and low ATP concentrations in tissues.