Makindo Medical Notes

Related Subjects: |Fat Metabolism |Glucose Metabolism |Protein metabolism |Glycolysis Krebs Electron Transport Chain |DNA replication |DNA structure in Nucleus |Cell Cycle |Mitosis and Meiosis |Ribosomes |Microtubules |Mitochondria |Smooth and Rough Endoplasmic Reticulum

Overview of Glucose Metabolism

Glucose metabolism involves the breakdown and utilization of glucose for energy production and other cellular processes. It is central to energy homeostasis and is tightly regulated by hormonal and enzymatic mechanisms.

Key Concepts

• Sources of Glucose:
  • Dietary Intake: Glucose is absorbed from the digestion of carbohydrates.
  • Glycogenolysis: Breakdown of glycogen stored in the liver and muscles.
  • Gluconeogenesis: Synthesis of glucose from non-carbohydrate precursors (e.g., amino acids, lactate, glycerol).
• Glycolysis:
  • Converts glucose to pyruvate, producing ATP and NADH.
  • Occurs in the cytoplasm of cells.
• Aerobic Respiration:
  • Includes the Krebs cycle and oxidative phosphorylation.
  • Occurs in the mitochondria and produces a large amount of ATP.
• Anaerobic Respiration:
  • Occurs when oxygen is limited, converting pyruvate to lactate.
  • Produces less ATP compared to aerobic respiration.
• Glycogen Metabolism:
  • Glycogenesis: Synthesis of glycogen from glucose for storage.
  • Glycogenolysis: Breakdown of glycogen to release glucose.
• Regulation of Glucose Metabolism:
  • Hormones: Insulin lowers blood glucose levels; glucagon and adrenaline/epinephrine raise blood glucose levels.
  • Enzymatic Regulation: Key enzymes include hexokinase, phosphofructokinase, and pyruvate kinase.

Detailed Pathways

• Glycolysis:
  • Glucose -> Glucose-6-phosphate (via Hexokinase).
  • Glucose-6-phosphate -> Fructose-6-phosphate.
  • Fructose-6-phosphate -> Fructose-1,6-bisphosphate (via Phosphofructokinase).
  • Fructose-1,6-bisphosphate -> Glyceraldehyde-3-phosphate + Dihydroxyacetone phosphate.
  • Glyceraldehyde-3-phosphate -> 1,3-Bisphosphoglycerate.
  • 1,3-Bisphosphoglycerate -> 3-Phosphoglycerate.
  • 3-Phosphoglycerate -> 2-Phosphoglycerate.
  • 2-Phosphoglycerate -> Phosphoenolpyruvate.
  • Phosphoenolpyruvate -> Pyruvate (via Pyruvate Kinase).
• Krebs Cycle (Citric Acid Cycle):
  • Pyruvate -> Acetyl-CoA (via Pyruvate Dehydrogenase).
  • Acetyl-CoA + Oxaloacetate -> Citrate.
  • Citrate -> Isocitrate.
  • Isocitrate -> Alpha-Ketoglutarate.
  • Alpha-Ketoglutarate -> Succinyl-CoA.
  • Succinyl-CoA -> Succinate.
  • Succinate -> Fumarate.
  • Fumarate -> Malate.
  • Malate -> Oxaloacetate.
• Oxidative Phosphorylation:
  • Occurs in the inner mitochondrial membrane.
  • Involves the electron transport chain and ATP synthase.
  • NADH and FADH2 donate electrons to the electron transport chain.
  • Proton gradient drives ATP synthesis from ADP and inorganic phosphate.
• Gluconeogenesis:
  • Occurs mainly in the liver and kidney.
  • Converts non-carbohydrate precursors into glucose.
  • Key substrates: lactate, glycerol, and glucogenic amino acids.
• Glycogen Metabolism:
  • Glycogenesis:
    • Glucose -> Glucose-6-phosphate.
    • Glucose-6-phosphate -> Glucose-1-phosphate.
    • Glucose-1-phosphate -> UDP-glucose.
    • UDP-glucose -> Glycogen (via Glycogen Synthase).
  • Glycogenolysis:
    • Glycogen -> Glucose-1-phosphate (via Glycogen Phosphorylase).
    • Glucose-1-phosphate -> Glucose-6-phosphate.
    • Glucose-6-phosphate -> Glucose (via Glucose-6-phosphatase in the liver).

Clinical Relevance

• Diabetes Mellitus:
  • Characterized by impaired insulin secretion or action.
  • Results in hyperglycemia and disrupted glucose metabolism.
• Hypoglycemia:
  • Low blood glucose levels due to excessive insulin or inadequate glucose production.
  • Symptoms include shaking, sweating, and confusion.
• Glycogen Storage Diseases:
  • Inherited disorders affecting glycogen metabolism.
  • Examples: Von Gierke's disease, Pompe disease.
• Metabolic Syndrome:
  • Cluster of conditions including insulin resistance, hyperglycaemia, and dyslipidemia.
  • Increases risk of cardiovascular disease and type 2 diabetes.

Summary

Understanding glucose metabolism is crucial for recognizing its impact on health and disease. Key pathways include glycolysis for immediate energy, aerobic and anaerobic respiration for ATP production, gluconeogenesis for glucose synthesis, and glycogen metabolism for storage and mobilization. Hormonal regulation, especially by insulin and glucagon, plays a significant role in maintaining glucose homeostasis, with implications for conditions such as diabetes, hypoglycemia, and metabolic syndrome.