Fig. 1.

Proposed mechanism for glutamine (GLN)-mediated induction of heat shock protein 70 (HSP70). GLN is metabolized via the hexosamine biosynthetic pathway (HBP) to UDP-N-acetylglucosamine (GlcNAc). Key enzymes in hexosamine pathway are glutamine fructose-6-amidotransferase (GFAT), polypeptide-O-β-acetylglucosaminyltransferase (OGT), and O-N-acetylglucosaminidase (O-GlcNAcase). Glucosamine can enter pathway distal to the GFAT enzyme. The inhibitors utilized to inhibit GFAT [6-diazo-5-oxonorleucine (DON)], OGT [alloxan and targeted small interfering (si)RNA], and O-GlcNAcase [O-(2-acetamido-2-deoxy-D-glucopyranosylidene)-amino-N-phenylcarbamate (PUGNAc)] are shown. HSF-1, heat shock factor 1.