Absence of diffusible inhibitor of glutamate dehydrogenase in the hepatocytes of Reye syndrome patients.

Hepatic glutamate dehydrogenase (GDH) activity was measured in postmortem specimens obtained from two stage V Reye syndrome patients and in three postmortem specimens of normal human liver. The Reye syndrome specimens showed the hepatic mitochondrial enzyme deficits in GDH and monoamine oxidase activities that are characteristic of Reye syndrome. GDH activity was linear with the amount of supernatant fraction added, both for Reye and normal liver preparations: moreover, the activities of mixtures of Reye and control supernatant fractions were the sums of the activities of the individual components. This means that the activity difference between Reye and normal GDH activity is not due to a diffusible inhibitor in the Reye hepatocytes or to an activator of GDH in the normal control hepatocytes. Serum obtained from six Reye cases during neurologic deterioration was added to normal hepatic GDH preparations to test for a serum inhibitor of FDH. Highly variable effects were found, with two serum samples producing marked inhibition and others showing weak inhibition, no effect, or stimulation of GDH activity. The inhibitor was not removed by charcoal treatment and most of the activity was retained by a 10,000 dalton Diaflo membrane, signifying either that the compound had a high molecular weight or that it was bound to serum protein. We conclude that the decreased activity of GDH in Reye hepatocytes is not due to an intracellular diffusible inhibitor, and that serum effects are quite variable and are not directly related to intracellular changes in GDH activity.