Glutamine--fructose-6-phosphate aminotransferase 1 (GFAT1)

Glutamine--fructose-6-phosphate aminotransferase 1 (GFAT1) is the first and rate-limiting enzyme in the hexosamine biosynthetic pathway and controls the flux of glucose into this pathway[1][2][6][7]. It catalyzes the conversion of fructose-6-phosphate and glutamine to glucosamine-6-phosphate, a precursor for UDP-N-acetylglucosamine, which is essential for protein N- and O-glycosylation[7]. GFAT1 activity is implicated in insulin resistance, protein homeostasis, and metabolic diseases such as diabetes and cancer[1][3]. This enzyme is regulated by feedback inhibition via UDP-N-acetylglucosamine; mutations that disrupt this regulation can significantly alter cellular metabolism and longevity in model systems[3]. GFAT1 is expressed in various tissues, with splice variants such as GFAT1-L showing tissue-specific expression[1].

Other names

Glutamine:fructose-6-phosphate amidotransferase 1Glutamine--fructose-6-phosphate transaminase 1GTPT1GFPT1CMSTA1GFAGFATGFAT1mGFPTGFPT1LMSLGCMS12Hexosephosphate aminotransferase 1

Inhibition of GFAT1 reduces production of UDP-N-acetylglucosamine, impacting protein glycosylation and metabolic pathways[3] - Gain-of-function mutations can activate the hexosamine pathway, altering protein homeostasis and cellular metabolism[3]