Glutamine--fructose-6-phosphate transaminase family
glutamine--fructose-6-phosphate transaminase family
The key enzyme in the de novo production of UDP-GlcNAc through the hexosamine biosynthesis pathway is glutamine--fructose-6-phosphate amidotransferase (GFPT). GFPT is present in all cellular organisms, including prokaryotes and eukaryotes, underscoring the importance of this enzyme and the HBP for normal cell function. The two mammalian paralogs, GFPT1 and GFPT2, share 75–80% amino acid sequence identity. GFPT1 is found more ubiquitously, whereas GFPT2 seems to have higher expression in tissues of the central nervous system. GFPT comprises an N-terminal 27 kDa glutaminase domain that catalyzes the hydrolysis of glutamine to glutamate and ammonia. The C-terminus harbors the 40 kDa isomerase domains that use ammonia to convert fructose-6-P (a glycolytic intermediate) to glucosamine-6-phosphate (GlcN-6-P). This reaction is the rate-limiting step of the de novo synthesis of hexosamines.