α-Ketoglutaramate: Increased Concentrations in the Cerebrospinal Fluid of Patients in Hepatic Coma

Abstract

α-Ketoglutaramate, a deaminated metabolite of glutamine not previously identified in biological tissues, was measured in the cerebrospinal fluid of human subjects and found to be increased three- to tenfold in patients with hepatic coma. When perfused into the cerebral lateral ventricles of rats, α-ketoglutaramate (10 mM) depressed the animals' nocturnal locomotor activity, and at higher doses induced circling behavior and myoclonus. The concentration of α-ketoglutaramate in cerebrospinal fluid appears to be a reliable diagnostic indicator of hepatic coma, and its accumulation may contribute to the pathogenesis of this disease.