A new variant of galactosemia: Galactose-1- phosphate uridylytransferase sensitive to product inhibition by glucose 1-phosphate

Abstract

In the erythrocytes of a patient with the clinical symptoms of galactosemia, a galactose-l-phosphate uridylyltransferase with abnormal kinetics was observed. Under standard assay conditions, the uridylyltransferase activity was almost normal initially and became completely inactivated within 30 min. The abnormal kinetics could be ascribed to a product inhibition by glucose 1- phosphate. The inhibition was produced by a variety of sugar phosphates, the most potent of which proved to be glucose 1- phosphate, mannose 1-phosphate, and fructose 6-phosphate. The variant galactose-l-phosphate uridylyltransferase was further characterized by a lowered affinity towards galactose 1-phosphate, non-Michaelis-Menten kinetics towards UDP-glucose, an increased thermal stability, and complete inactivity upon Cellogel electrophoresis. Speculation: The erythrocyte galactose-l-phosphate uridylyltransferase of the patient was almost completely inhibited at 50 /iM glucose 1- phosphate, which is within the range of the stationary glucose 1- phosphate concentration reported for liver. These findings suggest that the product inhibition of galactose-l-phosphate uridylyltransferase by glucose 1-phosphate is responsible for the impaired galactose-l-phosphate metabolism in the patient. © 1980 International Pediatric Research Foundation, Inc.