Urinary excretion of homocitric acid and methylhomocitric acid in propionic acidaemia: minor metabolic products of the citrate synthase aldol condensation reaction.

The identity of two formerly novel citric acid analogues, homocitric acid and methylhomocitric acid, in urine samples from patients with propionic acidaemia was confirmed by gas chromatography and mass spectrometry. Authentic reference substances were synthesized using a Reformatskii reaction. Homocitric acid and methylhomocitric acid were detected as minor metabolites in the urine samples from propionyl coenzyme A carboxylase deficient individuals. It was shown that these substances can be formed by the citrate synthase condensation reaction of alpha-ketoglutarate with acetyl coenzyme A and propionyl coenzyme A, respectively.