Expansion
Both enter glycolysis, and blocks in either pathway cause distinct disorders
Expansion
Fructose
- Fructokinase gives fructose-1-phosphate, then aldolase B splits it
- Deficiency of fructokinase gives essential fructosuria: benign
- Deficiency of aldolase B gives hereditary fructose intolerance: fructose-1-phosphate accumulates, trapping phosphate and inhibiting both glycogenolysis and gluconeogenesis. Presents at weaning with vomiting, hypoglycaemia and liver failure. Children develop a striking aversion to sweet foods and are notably free of dental caries
Galactose
- Galactokinase then galactose-1-phosphate uridyltransferase
- Galactokinase deficiency: galactitol accumulates in the lens, causing cataracts alone
- Classic galactosaemia (uridyltransferase deficiency): presents in the neonate on milk with vomiting, jaundice, hepatomegaly, cataracts, and a characteristic susceptibility to Escherichia coli sepsis
The organising principle is that the first enzyme deficiency is benign (the sugar is simply excreted) while the second is severe, because a phosphorylated intermediate accumulates and traps cellular phosphate.