Effects of exercise on the hexosamine biosynthetic pathway and glycosylation

Abstract

Minor amounts of glucose incorporated into the cells is metabolized via the hexosamine biosynthetic pathway, resulting in the production of uridine-5'-diphosphate-N-acetylglucosamine (UDP-GlcNAc), which is utilized as a donor substrate for the N-and O-linked glycosylation of extracellular and membrane proteins in the Golgi apparatus, or for the O-linked GlcNAc modification (O-GlcNAcylation) of intracellular proteins in the cytosol. In particular, O-GlcNAcylation, the addition of GlcNAc to serine/threonine residues, is reversibly regulated by the enzymatic activities of O-GlcNAc transferase (OGT) and O-GlcNAcase. Since OGT activity is sensitive to the intracellular UDP-GlcNAc level, flux via the hexosamine pathway influences O-GlcNAcylation. Actually, excess flux via the hexosamine pathway and resultant increased O-GlcNAcylation are associated with several pathophysiological conditions, including insulin resistance. To date, there are several studies addressing the effects of exercise on the hexosamine pathway and O-GlcNAcylation. Thus, this short review focuses on the relationships among exercise, the hexosamine pathway, O-GlcNAcylation, and insulin resistance.

Hepatic Metabolic Profiling of Lifelong Exercise Training Rats

“…42 Significant alternations were observed on a variety of nucleotide sugars (UDP-glucose, GDP-L-fucose and its precursor GDP-mannose, and UDP-alpha-D-galactose), and D-glucosamine 6-phosphate is widely involved in amino sugar and nucleotide sugar metabolism, galactose metabolism (UDPalpha-D-galactose and UDP-glucose), and fructose mannose metabolism (GDP-mannose and GDP-L-fucose). These metabolites are widely associated with protein glycosylation reactions 43 and may indicate increased protein biosynthesis required to support intense muscle exercise.…”