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. 2021 Oct 19;10(20):4792. doi: 10.3390/jcm10204792

Figure 2.

Figure 2

The Hexosamine Biosynthetic Pathway (HBP) and dynamic interplay between O-GlcNAc and O-phosphate. Once in the cells, glucose is enzymatically metabolized by Hexokinase (HK) to Glucose-6-Phosphate (Glc-6-P), which is then converted by Glc-6-P isomerase (GPI) into Glc-6-P to Fructose-6-phosphate (Fruc-6-P). About 3–5% of Fruc-6-P is metabolized to Glucosamine-6-phosphate (GlcN-6-P) by Glutamine Fructose-6-phosphate AmidoTransferase (GFAT). Glucosamine-6-Phosphate N-Acetyltransferase 1 (GNPNAT1) utilizes acetyl-CoA to convert GlcN-6-P into N-Acetylglucosamine-6-Phosphate (GlcNAc-6-P), which is then converted by Phospho-Acetyl Glucosamine Mutase 1 (AGM1) into N-acetylglucosamine-1-phosphate (GlcNAc-1-P). By utilizing Uridine Triphosphate (UTP), UDP-N-Acetylglucosamine Pyrophosphorylase (UAP) converts GlcNAc-1-P to Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). O-GlcNac modification and phosphorylation are reciprocal events because the site of attachment is the same or is adjacent to Ser/Thr residues. Two highly conserved enzymes mediate the addition and removal of the UDP-GlcNAc: OGlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively.