Glutamine--fructose-6-phosphate aminotransferase (isomerizing) (GFAT)

Glutamine--fructose-6-phosphate aminotransferase (isomerizing), commonly abbreviated as GFAT, is an enzyme that catalyzes the first and rate-limiting step of the hexosamine biosynthetic pathway, converting fructose-6-phosphate and glutamine to glucosamine-6-phosphate. This reaction is critical for the production of UDP-N-acetylglucosamine, a fundamental building block for glycoproteins, glycolipids, and chitin. GFAT has two major functional domains: an N-terminal glutaminase domain that hydrolyzes glutamine, and a C-terminal isomerase domain that facilitates sugar isomerization and aminotransfer. The enzyme plays a regulatory role in cellular glycosylation and is involved in metabolic pathways related to diabetes (insulin resistance), cancer, and chitin synthesis in fungi and arthropods. Due to its regulatory and biosynthetic importance, it is considered a therapeutic target, especially in the development of antifungal agents and possibly for metabolic diseases. Alterations in GFAT activity have implications in disease states such as diabetes and cancer.

Other names

Glucosamine-fructose-6-phosphate aminotransferase (isomerizing)Glucosamine-6-phosphate synthaseGlcN6P synthaseGFATGlmS

Inhibitors block conversion of fructose-6-phosphate and glutamine to glucosamine-6-phosphate, thereby inhibiting hexosamine pathway flux and downstream glycoconjugate biosynthesis.