Studies on the pathway from ornithine to proline in cultured skin fibroblasts with reference to the defect in hyperornithinaemia with hyperammonaemia and homocitrullinuria.

The reduction in the conversion of ornithine to proline by fibroblasts from a patient with hyperornithinaemia with hyperammonaemia and homocitrullinuria cannot be explained by a reduced uptake of exogenous ornithine, an altered total intracellular ornithine content, or reduced conversion of gamma-glutamate semialdehyde to proline. However, neither could the postulated defect in mitochondrial ornithine uptake be demonstrated using the digitonin method. Increasing the ornithine concentration in the medium increased the incorporation of 14C label from ornithine into protein in both the patient's and control cells. In the patient's cells the apparent Km for ornithine was ten times that of the controls, although the Vmax values were comparable. This result parallels the clinical response to ornithine supplementation.