Glutamine: Fructose-6-phosphate aminotransferase (GFAT) inhibitory activity of the anthocyanins present in black rice bran: a probable mechanism for the anti diabetic effect

Abstract

Glutamine: fructose-6-phosphate aminotransferase (GFAT) is the first and rate-limiting enzyme in the hexosamine biosynthetic pathway, which plays an important role in type 2 diabetes. GFAT controls the flux of glucose into the hexosamine pathway and catalyzes the formation of glucosamine 6-phosphate. Recent findings indicate that the flux through the hexosamine pathway, regulated by GFAT, is responsible for the development of diabetic vascular diseases, particularly diabetic nephropathy. Therefore, this enzyme is a therapeutic target for control of type 2 diabetes and the complications caused by the disease. Black rice bran contains many bioactive compounds and previous studies have shown that the black rice bran extract (BRBE) can decrease glucose levels in diabetic rats. Among the phenolic compounds, cyanidin-3-O-glucoside (COG) is the major anthocyanin in black rice. To elucidate the mechanism of antidiabetic effect of BRBE, the present study was designed to evaluate molecular interactions existing between six bioactive compounds extracted from black rice (Oryza sativa L.) viz. Cyanadin-3-O-Glucoside (COG), 6´-O-Feruloylsucrose (FLS), p-Coumaric acid (pCmA), Syringic acid (SYA), Sinapic acid (SPA) and Protocatechuic acid (PCA) with GFAT enzyme. The results indicated that of all the compounds extracted from black rice, COG and FLS show greater binding affinity than the native ligand glucose-6-phosphate. The other components of black rice also show a comparable binding affinity with the receptor. Thus the compounds extracted from black rice may produce significant antidiabetic effect by binding with GFAT.