USMLE

Fructose Metabolism

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Biochemical Pathways
  1. Glycolysis
  2. Citric Acid Cycle (TCA Cycle)
  3. Electron Transport Chain (ETC)
  4. Cori Cycle
  5. De Novo Purine Synthesis
  6. De Novo Pyrimidine Synthesis
  7. Purine Salvage
  8. Purine Excretion
  9. Ethanol Metabolism
  10. Pyruvate Metabolism
  11. HMP Shunt (Pentose Phosphate Pathway)
  12. Galactose Metabolism
  13. Sorbitol (Polyol) Pathway
  14. Urea Cycle
  15. Alanine (Cahill) Cycle
  16. Catecholamine Synthesis & Breakdown
  17. Homocysteine Metabolism
  18. Fatty Acid Synthesis (Citrate Shuttle)
  19. Fatty Acid Breakdown (Carnitine Shuttle)
  20. Propionic Acid Pathway
  21. Fructose Metabolism
  22. Regulation by Fructose-2,6-Bisphosphate (F-2,6-BP)
  23. Glycogenesis

Summary

Fructose metabolism describes the series of reactions used to breakdown fructose by cells in the body. This pathway begins with fructose, which is phosphorylated by the enzyme fructokinase to form fructose-1-phosphate, in a reaction that consumes 1 molecule of ATP. This first reaction is inhibited in patients with Essential fructosuria, a metabolic disorder characterized by a lack of fructokinase.

Next, aldolase B acts on fructose-1-phosphate to produce 2 products: dihydroxyacetone phosphate or DHAP, as well as glyceraldehyde. This breakdown reaction is inhibited in patients with Hereditary fructose intolerance, a metabolic disorder characterized by a lack of aldolase B.

Finally, both DHAP and glyceraldehyde are converted into G3P or glyceraldehyde-3-phosphate, an intermediate that connects to both the glycolytic and gluconeogenic pathways.

Key Points

  • Fructose Metabolism
    • Biochemical pathway used to break down fructose
      • Begins with fructose, obtained from diet and from polyol breakdown
      • Ends with glyceraldehyde-3-phosphate (G3P), which returns to glycolytic pathway
    • Reaction Pathway
      • Fructose + ATP  Fructose-1-P (F1P)
        • Catalyzed by Fructokinase
          • Defective in Essential Fructosuria
            • Buildup in unmetabolized fructose (benign)
        • Contrast F1P from F6P (produced in glycolysis)
      • Fructose-1-P → Dihydroxyacetone-P (DHAP) + Glyceraldehyde
        • Catalyzed by Aldolase B
          • Defective in Hereditary Fructose Intolerance
            • Buildup in unmetabolized fructose-1-P (toxic)
      • DHAP and Glyceraldehyde both converted into Glyceraldehyde-3-P (G3P)
        • 2 molecules of G3P are made per unit of fructose
        • G3P can enter glycolysis
        • Note that fructose metabolism bypasses phosphofructokinase (PFK) metabolism, which is the rate-limiting step of glycolysis
          • Fructose is the fastest monosaccharide cleared from the bloodstream because it bypasses this step
        • DHAP → Glyceraldehyde-3-P
          • Catalyzed by triose phosphate isomerase
        • Glyceraldehyde + ATP → Glyceraldehyde-3-P (used in glycolysis)
          • Catalyzed by triose kinase (triokinase)
        • Glyceraldehyde may also react with NADH to produce glycerol