The Role of Stress-Induced O-GlcNAc Protein Modification in the Regulation of Membrane Transport

Figure 1

The hexosamine biosynthesis pathway (HBP) and the O-GlcNAc posttranslational modification. (a) An estimated 1–3% of the total glucose enters HBP. The key enzymatic reaction of this pathway is the addition of an amino group from glutamine to fructose-6-phosphate by the rate-limiting enzyme glutamine-fructose-6-phosphate amidotransferase (GFAT). Following subsequent steps (addition of an acetyl group, converting 6-phosphate to 1-phosphate and finally the transfer to UDP), the end product of HBP is uridine diphosphate N-acetylglucosamine (UDP-GlcNAc). (b) The majority of UDP-GlcNAc is utilized in the endoplasmic reticulum and the Golgi apparatus for various glycolipid, glycoprotein, and glycan synthesis. A small, but significant, percentage of UDP-GlcNAc serves as a substrate pool for the dynamic, reversible posttranslational modification termed O-GlcNAc. A single N-acetylglucosamine group is attached to the Ser/Thr residues of target proteins by O-GlcNAc transferase, while the removal of this group is managed by the enzyme O-GlcNAcase. O-GlcNAc modification occurs predominantly in the cytoplasm and in the nucleus, and it is strongly dependent on substrate availability (i.e., the metabolic flux through HBP).

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