GLUCOSE-6-PHOSPHATASE DEPENDENT SUBSTRATE TRANSPORT IN THE GLYCOGEN-STORAGE-DISEASE TYPE-1A MOUSE

Glycogen storage disease type 1a (GSD-1a) is caused by a deficiency in microsomal glucose-6-phosphatase (G6Pase), the key enzyme in glucose homeostasis. A G6Pase knockout mouse which mimics the pathophysiology of human GSD-1a patients was created to understand the pathogenesis of this disorder, to delineate the mechanisms of G6Pase catalysis, and t o develop future therapeutic approaches. By examining G6Pase in the li ver and kidney, the primary gluconeogenic tissues, we demonstrate that glucose-6-P transport and hydrolysis are performed by separate protei ns which are tightly coupled. We propose a modified translocase cataly tic unit model for G6Pase catalysis.