Accumulation of 3-hydroxyisobutyric acid, 2-methyl-3-hydroxybutyric acid and 3-hydroxyisovaleric acid in ketoacidosis.

1. Urine and serum samples from patients with ketoacidosis of varying degree and etiology have been examined by gas chromatography and mass spectrometry. 2. In addition to 3-hydroxyisovaleric acid, relatively high concentrations of two analogous hydroxy acids, 3-hydroxyisobutyric acid and 2-methyl-3-hydroxybutyric acid, were found in the urine. 3. There were highly significant positive correlations between the excreted amounts of the three acids. 4. Experiments on rats with isotope-labelled compounds revealed that the acids were formed by the degradation of leucine, isoleucine and valine. 5. The accumulation of the hydroxy acids during ketoacidosis is probably caused by a similar derangement of the metabolism of all three branched-chain amino acids.