Glutamine–fructose-6-phosphate aminotransferase 2 (GFPT2)

Glutamine–fructose-6-phosphate aminotransferase 2 (GFPT2) is a cytosolic enzyme that catalyzes the first and rate-limiting step of the hexosamine biosynthetic pathway (HBP), converting fructose 6-phosphate and glutamine into glucosamine 6-phosphate. This reaction is crucial for generating UDP-N-acetylglucosamine (UDP-GlcNAc), a substrate needed for N- and O-linked glycosylation of proteins and lipids, which governs many aspects of protein folding, stability, and function. Unlike its paralog GFPT1, GFPT2 is primarily expressed in the central nervous system and in certain cancerous tissues, and its altered regulation is associated with cancer metastasis, diabetes, and nervous system disorders. GFPT2 is tightly regulated by feedback inhibition from UDP-GlcNAc, but is less sensitive to inhibition than GFPT1, which has implications for its tissue- and disease-specific roles. Dysregulation or overexpression of GFPT2 contributes to tumor progression, especially through effects on glycosylation-mediated signaling and cell adhesion. Although essential for basic cellular functions, it is being investigated as a potential therapeutic target in oncology and metabolic diseases.

Other names

GFPT2GFAT2Glutamine-fructose-6-phosphate transaminase 2D-fructose-6-phosphate amidotransferase 2Hexosephosphate aminotransferase 2glucosamine–fructose-6-phosphate aminotransferase 2Glutamine:fructose-6-phosphate amidotransferase 2

Enzyme inhibition (modulating the rate-limiting step of the hexosamine pathway; in principle, inhibition reduces UDP-GlcNAc availability and downstream protein glycosylation)