Synthesis of Amino Sugars the Hexosamine Signaling Pathway.
Glycosaminoglycans are large complexes of negatively charged polysaccharide chains formed from amino-sugars or hexosamines. The latter are made from F-6-P and an amino group from glutamine. Glycosaminoglycans are the body's ground substance" which supports various protein structures and provides a stable aqueous environment in our tissues. Glycosaminoglycan chains are formed from repeating hexosamine units. These units come from activated hexosamines, that is, they are formed by joining UDP-hexosamine units, driven forward by the energy in the high-energy phosphate bonds in UTP. This resembles synthesis of glycogen from UDPglucose (UDPG).
In most tissues about 2-5 % of the F-6-P formed enters hexosamine synthesis. The first and rate-determining step is coupling of an amino group from glutamate to F-6-P. This is catalyzed by glutamine: fructose-6-phosphate amidotransferase or GFAT. Glucosamine-6-P then acetylated through exchange with acetyl-CoA forming N-acetylglucosamine-6-phosphate. An isomerase converts the 6-phosphate to N-acetyl-glucoseamine-1-phosphate. Finally, this reacts with UTP, forming UDP-N-acetylglucosamine (UDP-GlcNAc).