Sugar Disorders

Fructose, Galactose and Mannose Metabolism

galactosemia
  • Fructose intolerance:
    • Aldolase B deficiency causes accumulation of F1P
    • Depletes liver phosphates, no phosphate no glycogenolysis
    • ATP drops so no gluconeogenesis. Activates glycolysis, causes lactic acidosis.
    • Hypoglycemia because of glycogenolysis and gluconeogenesis inhibition.
    • Jaundice, cirrhosis, vomiting.
    • Develops distaste for sweet stuff.
  • Essential fructosuria:
    • Fructokinase defect causes fructose to appear in urine.
    • Benign because fructose doesn't enter cells.
  • Classical Galactosemia:
    • Galactose-1-phosphate uridyltransferase defect causes accumulation galactose (appears in blood, urine, reduced to galactitol in lens).
    • Galactose enters eye, aldose reductase changes it to galactitol (can't leave).
    • Galactitol accumulates in lens and causes cataracts (Diabetics have glucose → sorbitol which causes cataracts).
    • Failure to thrive, jaundice, hepatomegaly, infantile cataracts, mental retardation.
    • Treatment: no galactose or lactose (glucose and galactose).
    • Enzymes involved in galactose → glucose:
      • Galactokinase: Gal → Gal-1-P. Deficiency causes ↑ galactose (cataracts).
      • Galactose-1-phosphate uridyltransferase: Gal-1-P → UDP-Gal. Deficiency (classic galactosemia) causes ↑ galactose (cataracts) + Gal-1-P (growth failure, mental retardation, liver damage).
      • UDP-Gal epimerase: UDP-Gal → UDP-Glc. Deficiency of which causes ↑ galactose (cataracts) + Gal-1-P (growth failure, mental retardation, liver damage) + UDP-Gal.
  • Lactose intolerance: lactase deficiency (blacks, asians lose brush-border enzyme). Lactose = Gal-Glc, dietary source of galactose.