Immunochemical analysis of carbamyl phosphate synthetase I and ornithine transcarbamylase deficient livers: elevated N-acetylglutamate level in a liver lacking carbamyl phosphate synthetase protein.

Liver tissue from 3 patients with carbamyl phosphate synthetase I deficiency and 11 patients with ornithine transcarbamylase deficiency was analyzed by Western blots for the presence of carbamyl phosphate synthetase I and ornithine transcarbamylase cross-reactive material with anti-rat enzyme antibodies. One patient with carbamyl phosphate synthetase I deficiency had no cross-reactive material with the antibody to this enzyme, one had reduced amounts, and one had similar to normal amounts. Only one of the patients with ornithine transcarbamylase deficiency had apparently normal amounts of enzyme protein in his liver, another patient had markedly reduced amounts, and the other nine patients had traces or absence of reactive ornithine transcarbamylase protein. N-acetylglutamate content in the carbamyl phosphate synthetase I deficient liver with absent enzyme protein, was higher (98.4 nmol/g) than that measured in 5 normal controls (41.6 +/- 19.3 mean +/- SD, n = 5) and much higher than the N-acetylglutamate level (2.2 nmol/g) in another carbamyl phosphate synthetase I deficient liver with normal amounts of enzyme protein. Hepatic N-acetylglutamate content in 3 patients with complete ornithine transcarbamylase deficiency was below the normal mean but within 2 standard deviations from the mean (8.5-12.8 nmol/g) whereas it was higher (30.7 nmol/g) in another partial ornithine transcarbamylase deficient patient. Most patients with ornithine transcarbamylase deficiency have markedly reduced or undetectable enzyme protein in their liver, therefore. Western blot analysis could help to establish this diagnosis in most patients. Absent carbamyl phosphate synthetase I enzyme protein may have caused elevation of the hepatic content of its cofactor, N-acetylglutamate, by an as yet unknown mechanism.