Glycogen Metabolism Overview

Glycogen Metabolism

• Glycogen is a homopolymer of α-D-glucopyranose.
• Liver glycogen is broken down for distribution to other organs via the bloodstream and maintaining proper blood glucose levels.
• Muscle glycogen is used to produce energy.

Glycogen Breakdown (Glycogenolysis)

• Glycogen phosphorylase catalyzes phosphorolysis, cleaving bonds by substituting a phosphate group. This forms glucose-1-phosphate.
• Pyridoxal phosphate is an essential cofactor, derived from Vitamin B6.
• Debranching enzyme (oligo(α-1,6→α-1,4) glucantransferase) removes branches, cleaving α-1,6 glycosidic bonds.
• Phosphoglucomutase converts glucose-1-phosphate to glucose-6-phosphate.

Release of Glucose as Glucose-1-P

• Glucose released is already phosphorylated, preventing it from leaving the cell.
• It readily enters glycolysis after converting to glucose-6-phosphate by phosphoglucomutase.

Re-modeling of Glycogen

• Restructuring occurs near branch points to prepare for further degradation.
• The action of glycogen phosphorylase continues until only 4 residues are left from the branch point.

De-branching

• α-1,6-glycosidic bonds are cleaved by α-1,6-glucosidase.
• Released glucose from de-branching is converted to glucose-6-phosphate, entering glycolysis.

Glycogen Synthesis (Glycogenesis)

• Enzymes involved are UDP-glucose pyrophosphorylase, glycogen synthase, and branching enzyme.
• UDP-glucose is the activated form of glucose, serving as a glucose donor for glycogen synthesis.

Formation of Glucose-6-P

• Hexokinase converts glucose into glucose-6-phosphate using ATP.

Conversion of Glucose-6-P to Glucose-1-P

• Phosphoglucomutase converts glucose-6-phosphate into glucose-1-phosphate.

Formation of UDP-Glucose

• UDP-glucose pyrophosphorylase converts glucose-1-phosphate and UTP to UDP-glucose and PPi.

Addition of Glucose to Glycogen

• Glycogen synthase links glucose molecules to a growing glycogen chain.
• It requires a primer chain of at least 4 glucose molecules.
• Glycogenin synthesizes the initial primer.

Branching

• Branching enzyme creates branches by transferring segments of 7 glucosyl residues in length
• New branch point is at least 4 residues away from another.

Hormonal Regulation of Glycogen Metabolism

• Insulin promotes glycogen synthesis and inhibits glycogen breakdown.
• Epinephrine (muscle) and glucagon (liver) induce glycogen breakdown.
• Glycogenolysis and glycogenesis are reciprocally regulated. Normal blood glucose is 70-100 mg/100 mL.

Gluconeogenesis

• Synthesizes glucose from non-carbohydrate precursors (e.g., pyruvate, lactate, glycerol, amino acids).
• Enzymes differ in irreversible steps from glycolysis to avoid futile cycles.
• Primarily occurs in the liver and kidney.

Cori Cycle

• Occurs during intense muscular activity (hypoxia).
• Lactate travels from muscles to liver, where gluconeogenesis transforms it to glucose.
• Glucose returns to muscles for glycogenesis or glycolysis.
• Prevents lactic acidosis and muscle cramps

Photosynthesis

• Autotrophic organisms convert CO₂ into sugars using light energy.
• Process occurs in chloroplasts.

Light Reactions (Photosynthesis)

• Converts light energy into chemical energy (ATP and NADPH).
• Occurs in thylakoid membranes.

Dark Reactions (Photosynthesis)

• CO₂ is fixed and reduced to form sugars.
• Uses ATP and NADPH.
• Occurs in the stroma.