Glycogen Metabolism

Glycogen Metabolism

Glycogen is the storage form of glucose in animals, equivalent to starch in plants. It is a highly branched polymer of glucose with α-1,4 glycosidic bonds in chains and α-1,6 bonds at branch points. Stored in liver (glucose reservoir for blood sugar) and muscle (fuel for muscle contraction).

Glycogenesis (Synthesis)

Requires UDP-glucose as the activated glucose donor.

  1. Glucose → G6P (Glucokinase/Hexokinase)
  2. G6P → G1P (Phosphoglucomutase)
  3. G1P + UTP → UDP-glucose + PPi (UDP-glucose pyrophosphorylase) — driven by pyrophosphatase
  4. UDP-glucose → added to glycogen chain by Glycogen Synthase (rate-limiting; adds α-1,4 links)
  5. Branching enzyme: transfers 6–7 residues to C6, creating α-1,6 branch point (every 8–12 residues)

A protein primer (glycogenin) serves as initiator — glycogen synthase cannot start a new chain from scratch.

Glycogenolysis (Breakdown)

  1. Glycogen Phosphorylase (rate-limiting): Cleaves α-1,4 bonds releasing Glucose-1-phosphate (using inorganic phosphate, not water — phosphorolysis). Cannot pass within 4 residues of branch point.
  2. Debranching enzyme (bifunctional): Transfers 3 residues to chain end (transferase), then cleaves α-1,6 bond (glucosidase) releasing free glucose (not phosphorylated). Free glucose from branches exits cells; G1P is retained.
  3. G1P → G6P (Phosphoglucomutase)
  4. In liver: G6P → Glucose (G6Pase) → exported to blood
  5. In muscle: G6P → enters glycolysis directly (no G6Pase)

Hormonal Regulation

  • Glucagon/Epinephrine (cAMP cascade): Receptor → Gs protein → Adenylyl cyclase → ↑cAMP → PKA → phosphorylates: ① Phosphorylase kinase (active) → phosphorylates Glycogen Phosphorylase → active (phospho-a form) → glycogenolysis ↑ ② Glycogen Synthase (inactive phospho-b form) → glycogenesis ↓
  • Insulin: Activates Protein Phosphatase 1 → dephosphorylates Phosphorylase (inactive) and Glycogen Synthase (active) → promotes glycogenesis and stops glycogenolysis.
  • AMP (muscle): Directly activates Glycogen Phosphorylase b without phosphorylation (local energy sensor).

Glycogen Storage Diseases (GSDs)

  • Type I (Von Gierke): G6Pase deficiency; cannot release glucose from liver
  • Type II (Pompe): Lysosomal α-1,4-glucosidase (acid maltase) deficiency; glycogen in all organs; cardiomegaly
  • Type III (Cori/Forbes): Debranching enzyme deficiency; abnormal short outer branches
  • Type V (McArdle): Muscle Phosphorylase deficiency; exercise intolerance, myoglobinuria
  • Type VI (Hers): Liver Phosphorylase deficiency; mild hypoglycemia

Quiz - Exam Preparation Strategy

When studying Quiz for your final board exams, it is critical to focus on the core concepts and fundamental formulas. Relying strictly on NCERT textbook solutions and practicing previous year questions (PYQs) is the proven methodology for scoring high marks. Avoid rote memorization and instead focus on the logical application of the theories presented in this chapter.

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