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

In the erythrocytes of a patient with the clinical symptoms of galactosemia, a galactose-1-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-1-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.