Insights into Neuronal Cell Metabolism Using NMR Spectroscopy: Uridyl Diphosphate N-Acetyl-Glucosamine as a Unique Metabolic Marker

摘要

Uridyl diphosphate N-acetyl-glucosamine (UDP-GlcNAc) was discovered 1953 and is a nucleotide or a so-called activated sugar that is produced by the hexosamine biosyn-thetic pathway (HBP). It was proposed that such activated sugars provide important information about the metabolic state of a cell, and in particular reflects possible pathological disorders. UDP-GlcNAc delivers GlcNAc units for the biosynthesis of N and O glycans, and it gained even more biological importance as a metabolic precursor along with the discovery of O GlcNAcylation. O GlcNAcylation is a post-translational modification of nuclear and cytosolic proteins wherein UDP-GlcNAc covalently links a GlcNAc residue to a serine or threonine residue, similar to phosphorylation. This modification plays an important role in many fundamental cellular processes and its dysregulation may be associated with human diseases such as cancer or diabetes. In the brain, especially in the neurons, the availability of UDP-GlcNAc is very important because O GlcNAcylation of the Tau protein is assumed to counteract the development of Alzheimer's disease.