Glycogen Metabolism and Pathways

Glycogen Metabolism, Disaccharides, and Pentose Phosphate Pathway

• Glycogen's Importance: Crucial for maintaining blood glucose levels.
• Glycogen Synthesis and Degradation: Pathways involved in these processes need understanding.
• Glycogen Storage Diseases: Various diseases stemming from defects in glycogen metabolism.
• Fructose and Galactose Metabolism: Mechanisms involved in the body's processing of these sugars.
• Enzymes in Inborn Errors: Understanding the role of specific enzymes in fructose and galactose metabolism.
• Pentose Phosphate Pathway: Comprehensive understanding of the pathway and its associated enzymes.
• Hormonal Regulation: How hormones regulate metabolism and the enzymes involved.

Glycogen

• Carbohydrate Storage: Glycogen is the primary storage form of carbohydrates in animals.
• Polymer Structure: A branched polymer of glucose units (a1-4-linked and a1-6-linked branches).
• Storage Locations: Predominantly stored in liver and muscles.
• Liver Glycogen's Role: Maintains blood glucose during fasts.
• Muscle Glycogen's Role: Provides energy to muscles.

Glycogen Structure

• UDP-Glucose: Supplies glucose units for glycogen synthesis.
• Attachment Points: New glucose molecules are added to non-reducing ends.
• Reducing End: Oxidizable end of the glucose molecule.
• Branched Structure: Allows for quicker glycogen release.

Glycogen Synthesis

• Regulation by Glycogen Synthase: Enzyme that catalyzes glycogen synthesis.
• Glucose-1-Phosphate: A substrate used during glycogen synthesis.
• UDP-Glucose: A substrate used by glycogen synthase.
• Glycogen Synthase Activity: Active in dephosphorylated form; positively regulated by insulin.

Glycogenolysis

• Glycogen Phosphorylase: Key enzyme for glycogen breakdown.
• Inorganic Phosphate (Pi): Cleaves a1-4 bonds to produce glucose-1-phosphate.
• Debranching Enzyme: Removes branches.
• Amylo-1,6-glucosidase: Enzyme activity within the debranching enzyme.
• Glucose-6-phosphate: Key product of glycogen breakdown.

Glycogen Storage Diseases

• Impaired Glycogen Breakdown: Various tissues and organs impacted and their subsequent problems.
• Liver Deficiencies: Enlarged liver (hepatomegaly), hypoglycemia, lactic acidosis often associated.
• Muscle Deficiencies: Exercise intolerance and potential respiratory problems.

Glucose-6-phosphatase

• Role in Gluconeogenesis and Glycogenolysis: Provides free glucose to blood.
• Deficiency (von Gierke Disease): Leads to profound hypoglycemia and other complications.

Glucagon-Insulin Axis

• Catabolic Hormones: Glucagon and epinephrine break down glycogen to release glucose.
• Anabolic Hormone: Insulin promotes glycogen synthesis for energy storage.
• Fasting/Fed States: Hormonal differences during fasting versus fed states.

Galactose Metabolism

• Transport: Galactose uses a specific transporter system.
• Metabolism: Converts galactose to glucose intermediates inside the body.
• Enzymes: Galactokinase and uridyltransferase crucial in galactose metabolism.

Galactosemia

• Deficiencies: Genetic disorders affecting galactose metabolism, characterized by galactose accumulation.
• Clinical Symptoms: May cause cataracts, intellectual disability, liver damage and other complications.

Fructose Metabolism

• Absorption: Fructose transported differently, unlike other sugars, and does not directly trigger insulin production.
• Metabolism in Liver: Can be converted to glucose through gluconeogenesis and glycolysis, not reliant on insulin.
• Disorders of Fructose Metabolism: Fructose-1-phosphate accumulates, leading to severe hypoglycemia and other problems.

Pentose Phosphate Pathway

• NADPH Generation: Produces NADPH, a crucial reducing agent for various metabolic roles.
• Ribose-5-Phosphate Production: Provides a precursor for nucleotide synthesis.
• Oxidative Stage: NADPH is generated, followed by subsequent steps for further conversions.
• Non-oxidative Stage: Reversible reactions convert pentose phosphates to other intermediates.

Glucose-6-Phosphate Dehydrogenase Deficiency

• Genetic Deficiency: X-linked disorder primarily affecting red blood cells.
• Consequences: Oxidative stress, haemolytic anaemia resulting from oxidative damage due to deficiency.