Metabolism of Fructose and Galactose

Fructose Metabolism - Sweet & Swift

• Sources: Fruits, honey, high-fructose corn syrup, sucrose.
• Primary Site: Liver.
• Pathway:
  • Fructose enters hepatocytes via GLUT5 (insulin-independent).
  • Fructokinase (FK): Phosphorylates fructose.
    • Fructose + ATP $\rightarrow$ Fructose-1-Phosphate (F-1-P) + ADP
  • Aldolase B: Cleaves F-1-P.
    • Fructose-1-Phosphate $\rightarrow$ Dihydroxyacetone Phosphate (DHAP) + Glyceraldehyde
  • DHAP enters glycolysis.
  • Glyceraldehyde is phosphorylated by Triokinase (Glyceraldehyde + ATP $\rightarrow$ Glyceraldehyde-3-P + ADP), then enters glycolysis.
• 📌 Mnemonic: 'FructoKinase Kicks it off, Aldolase B Breaks it down.'

⭐ Fructose metabolism bypasses Phosphofructokinase-1 (PFK-1), the major rate-limiting step of glycolysis. This allows rapid fructose processing, potentially leading to ↑ VLDL synthesis and lipogenesis.

Galactose Metabolism - Milky Way Fuel

• Sources: Primarily lactose (milk, dairy), hydrolyzed to galactose & glucose.
• Leloir Pathway: Converts galactose to glucose-1-phosphate. Key enzymes:
  • Galactose + ATP $\xrightarrow{\text{Galactokinase (GALK)}}$ Galactose-1-P + ADP
  • Galactose-1-P + UDP-Glucose $\xrightarrow{\text{GALT (Galactose-1-P Uridyltransferase)}}$ UDP-Galactose + Glucose-1-P

    ⭐ UDP-glucose is essential for the conversion of galactose-1-phosphate to glucose-1-phosphate via GALT.

  • UDP-Galactose $\xrightarrow{\text{GALE (UDP-Galactose-4-Epimerase)}}$ UDP-Glucose (regenerated for GALT)
• Fate: Glucose-1-P $\rightarrow$ Glucose-6-P (enters glycolysis/gluconeogenesis) or glycogenesis.
• Clinical Note: Enzyme deficiencies (esp. GALT) cause galactosemia (cataracts, liver damage, intellectual disability).
• 📌 Mnemonic (Leloir enzymes): Kinase, Transferase, Epimerase (GalacKTE).

Disorders of Fructose Metabolism - Fruity Faults

• Two main disorders disrupt fructose metabolism, primarily due to enzyme deficiencies.

⭐ In Hereditary Fructose Intolerance, accumulation of Fructose-1-Phosphate inhibits glycogenolysis and gluconeogenesis, leading to severe hypoglycemia on fructose ingestion.

Disorders of Galactose Metabolism - Galactic Glitches

• Galactose metabolism disorders result from enzyme deficiencies, leading to galactitol accumulation.
  • Galactitol causes osmotic damage, notably cataracts.
• 📌 Galactosemia Affects Liver & Tiny tots (Classical GALT deficiency).

⭐ Newborn screening for classical galactosemia (GALT deficiency) is crucial to prevent severe complications like liver failure, sepsis, and intellectual disability.

High‑Yield Points - ⚡ Biggest Takeaways

• Essential fructosuria (fructokinase deficiency): benign; fructose in urine (reducing sugar).
• Hereditary Fructose Intolerance (aldolase B deficiency): Fructose-1-P accumulation inhibits glycogenolysis & gluconeogenesis, causing severe hypoglycemia, vomiting post fructose.
• Fructose metabolism bypasses PFK-1, a key rate-limiting step of glycolysis.
• Galactokinase deficiency: galactitol accumulation from unmetabolized galactose causes infantile cataracts.
• Classic galactosemia (GALT deficiency): Galactose-1-P accumulation causes cataracts, hepatomegaly, E. coli sepsis, intellectual disability.