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).