| GFAT1, glutamine:fructose-6-phosphate aminotransferase 1, is the rate-limiting enzyme of the hexosamine biosynthesis pathway. This enzyme catalyzes the conversion of fructose-6-phosphate and glutamine to glucosamine-6-phosphate and glutamate. The hexosamine biosynthesis pathway generates the building blocks for protein and lipid glycosylation. Furthermore, studies suggest that increased activity of this pathway is a contributing factor to hyperglycemia-induced insulin resistance. GFAT1 is more active in non-insulin-dependent diabetes mellitus (NIDDM) patients. Transgenice mice overexpressing this enzyme in skeletal muscle and adipose tissue show an insulin resistance phenotype. GFAT2, an isoenzyme of GFAT1, was later identified. Studies show that the regulation of GFAT2 is different from that of GFAT1, suggesting differential regulation of the hexosamine pathway in different tissues. |
