Glycogen Metabolism

• Glycogen

  Branched polymer of glucose, "animal starch"
• Glycogen catabolism

  1. Glycogen phosphorylase breaks 1→4 bonds using Pi

  2. Debranching enzyme hydrolyses 1→6 bonds and transfers 3 glucose units to core

  3. Phosphoglucomutase interconverts G-1-P and G-6-P

  4. Entry into glycolysis
• Phosphorolysis

  Breaking bonds using Pi, may be compared to hydrolysis
• Glycogen phosphorylase

  • Has deep cleft active site
  • Uses pyridoxal phosphate as prosthetic group
  • 3 isozymes: muscle, brain, liver
  • Processive enzyme, can rapidly mobilise glycogen
• Phosphorylase can't break 1→6 bonds or 1→4 bonds within 4 units of branch point, leading to limit dextrins
• Glycogen anabolism (glycogenesis)

  1. Glucose-1-phosphate converted to UDP-glucose by UDP-glucose pyrophosphorylase

  2. Glycogen synthase adds UDP-glucose to existing glycogen chains via α(1→4) bonds

  3. Glycogenin builds initial 8 unit primer chain, then branching enzyme attaches heptamer via α(1→6) bond
• Glycogenesis is reversible but doesn't happen in practice (McArdle's disease shows this)
• Glycogenesis requires nucleotide triphosphates like ATP, UTP
• Glycogen synthase can't start new chains or make α(1→6) branches
• Glycogen has 12 tiers in a typical molecule
• Glycogenolysis

  Breakdown of glycogen to glucose-1-phosphate
• Glycogenesis

  Synthesis of glycogen from glucose
• What is glycogen commonly referred to as in animals?

  animal starch
• What type of bonds connect the main chain of glycogen, and what type of bonds create branch points?

  The main chain of glycogen is connected by α(1→4) glycosidic bonds, and branch points are created by α(1→6) glycosidic bonds
• How often does branching occur in the structure of glycogen?

  Branching in glycogen occurs every 8-12 glucose units
• What percentage of liver and muscle mass can glycogen make up?

  Glycogen can make up to 10% of liver mass and 1-2% of muscle mass
• What enzymes are involved in glycogen catabolism, and what is the key difference between hydrolysis and phosphorolysis in this context?


  Glycogen phosphorylase is involved in glycogen catabolism. The key difference is that hydrolysis uses water to break bonds (forming free glucose), whereas phosphorolysis uses inorganic phosphate to break bonds, forming glucose-1-phosphate
• Why does glycogenolysis use phosphorolysis instead of hydrolysis?


  Glycogenolysis uses phosphorolysis because it conserves energy. Phosphorolysis directly forms glucose-1-phosphate without the need for ATP, whereas hydrolysis followed by phosphorylation to glucose-6-phosphate requires ATP
• What are the limitations of glycogen phosphorylase in breaking down glycogen?

  Glycogen phosphorylase cannot break α(1→6) bonds at branch points and cannot break α(1→4) bonds within 4 units of a branch point
• What role do the debranching enzymes play in glycogen catabolism?

  Debranching enzymes transfer 3 glycosyl units to the core chain and hydrolyze the single α(1→6) linked glucose, allowing further degradation by glycogen phosphorylase
• What type of structure does glycogen have, and how many glucose units typically form a chain before branching occurs?

  Glycogen has a helical structure with 12-14 glucose units typically forming a chain between branch points
• What is the approximate diameter of a glycogen molecule?

  The diameter of a glycogen molecule is approximately 10-40 nanometers
• What is the primary functional role of the enzyme phosphoglucomutase in glycogen metabolism?

  Phosphoglucomutase plays a critical role in glycogen metabolism by converting glucose-1-phosphate to glucose-6-phosphate, facilitating its entry into glycolysis
• How does the enzyme glycogen synthase contribute to glycogen anabolism?


  Glycogen synthase catalyzes the formation of α(1→4) glycosidic bonds in glycogen, adding glucose units to an existing chain. It cannot start chains or make α(1→6) branches
• What role does the branching enzyme play in glycogen synthesis?

  The branching enzyme (glycosyltransferase) reattaches a heptamer of glucose units via an α(1→6) bond during glycogen synthesis, enhancing the solubility and accessibility of glycogen
• How are the enzymes involved in glycogen catabolism regulated or activated?

  Glycogen phosphorylase, the key enzyme in glycogenolysis, is activated by hormones like glucagon and adrenaline, which signal the need for glucose production during fasting or stress
• Explain the significance of glycogen’s rapid mobilisation capability in metabolic processes


  Glycogen’s branched structure allows for rapid mobilization of glucose, providing quick energy supply during sudden demand, such as intense physical activity or fasting
• What is the sole purpose of glucose-6-phosphatase?

  To make free glucose that can be released into the blood
• What is glucose-6-phosphatase

  An enzyme complex on the endoplasmic reticulum (ER) membrane
• What is the primary function of glucose-6-phosphatase in the liver?

  The primary function of glucose-6-phosphatase in the liver is to convert glucose-6-phosphate into free glucose, which is then released into the bloodstream to help maintain blood sugar levels, especially during fasting
• Where is the enzyme glucose-6-phosphatase located within the cell?

  Glucose-6-phosphatase is located in the endoplasmic reticulum (ER) of liver and kidney cells
• How is glucose-6-phosphate transported into the endoplasmic reticulum?

  Glucose-6-phosphate is transported into the endoplasmic reticulum by a specific transport protein known as the glucose-6-phosphate transporter (G6PT)
• Describe the cooperation between glucose-6-phosphatase and transport proteins in glucose regulation

  Glucose-6-phosphatase cooperates with transport proteins to regulate glucose levels. G6PT transports glucose-6-phosphate into the ER where glucose-6-phosphatase converts it into glucose. This glucose is then transported back into the cytosol by other transport proteins, allowing it to enter the bloodstream
• What is the role of glycogen in muscle cells compared to liver cells?

  In muscle cells, glycogen provides a quick source of energy during physical activity by being broken down to glucose, which is used locally within the muscle. In liver cells, glycogen helps regulate blood glucose levels for the entire body by releasing glucose into the bloodstream
• Explain the process of glycogen synthesis (glycogenesis)


  Glycogenesis is the process of converting glucose into glycogen for storage. It involves the enzyme glycogen synthase, which adds glucose units to a growing glycogen chain through α(1→4) glycosidic bonds, and the branching enzyme which introduces α(1→6) glycosidic bonds to form branches in the glycogen molecule
• What is the role of glycogenin in glycogen synthesis?

  Glycogenin serves as a primer for glycogen synthesis. It starts the process by creating a short chain of about 8 glucose residues, which then provides the foundation for further extension by glycogen synthase
• What is the impact of hormones like glucagon and adrenaline on glycogen metabolism?

  Hormones such as glucagon and adrenaline stimulate glycogenolysis, the breakdown of glycogen into glucose. This is especially important during stress or fasting when the body needs additional glucose for energy