Fig. 1: Hexosamine biosynthetic pathway (HBP).
From: Exploring the metabolic signaling network of GFPT in cancer
The HBP branches from glycolysis, utilizing ~2–5% of the glucose entering the cell. The enzyme GFPT, which has two catalytic domains (N-terminal and C-terminal), catalyzes the committed step of the HBP by converting fructose-6-phosphate (Fru-6-P) and glutamine (Gln) into glucosamine-6-phosphate (GlcN-6-P) and glutamate (Glu) as by-products. GlcN-6-P is then acetylated by glucosamine-6-phosphate N-acetyltransferase (GNPAT) to form N-acetylglucosamine-6-phosphate (GlcNAc-6-P), which is subsequently converted into GlcNAc-1-P by phosphoglucomutase (PGM3). Using UTP from nucleotide metabolism, uridine diphosphate N-acetylhexosamine pyrophosphorylase (UAP) catalyzes the conversion of GlcNAc-1-P to uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), a substrate for O-GlcNAcylation (a post-translational modification) mediated by O-GlcNAc transferase (OGT), as well as for N- and O-linked glycosylation.
