the formation of hydrogen bonds that stabilize the crystalline structure of this polymer, providing greater resistance to fracture. Nevertheless, in prokaryotic metabolism, the hexosamine biosynthesis pathway follows a different reaction step, in which a different enzyme acts upon the same characteristic substrates (Figure 1). In prokaryotes, the phosphate transfer from the 6-carbon to the 1-carbon takes place before the acylation, such that the substrate of carbon-adding reaction is Glucosamine-1-phosphate rather than D-glucosamine-6-phosphate. This time, the enzyme responsible for the acetylation is the bifunctional protein glmU (N-Acetylglucosamine-1-phosphate uridyltransferase), that also catalyzes the addition of UDP to the phosphate group on N-Acetyl-D-Glucosamine-1-Phosphate. In humans, glucosamine-phosphate N-acetyltransferase is a dimer with two identical subunits, and is encoded in the gene GNPNAT (HGNC Symbol). More specifically, the enzyme is strongly expressed in the liver, stomach and gastrointestinal tract tissues, and within the cell, it is located in endosomes and in the Golgi apparatus (by manual annotation). Mechanism The molecular structure of the reaction catalyzed by GNA is shown below, with the transferred acetyl group in blue. The general reaction mechanism postulated for protein N-end acetylation (inspired by lysine acetylation mechanism) with Acetyl-CoA involves a nucleophilic attack of the amino group (in this case from D-Glucosamine-6-phosphate) on the terminal carbonyl in the carbon transfer, leading to the formation of a carbon tetrahedral intermediate. The reaction proceeds with the restoration of the carbonyl by removing the CoA as a leaving group, such that now the acetyl group is connected to the amino group in the other substrate. Specifically for this N-acetyltransferase catalysts, studies with S. cerevisiae GNA enzyme have shown that some specific amino acids contribute to substrate binding, increased nucleophilicity of the amino group and finally catalysis, which supports the postulated mechanism described above. Glu98, Asp99, and Ile100 polarize the carbonyl bond in the Acetyl-CoA, increasing the carbon electrophilicity as well as stabilizing the carbon tetrahedral intermediate. Tyr143 is responsible for stabilizing the thiolate anion, favoring the S-CoA as a leaving group from the tetrahedral carbon. Finally, Asp134 enhances the nucleophilicity of the amino group in D-Glucosamide-6-phosphate by donating electron density to the nitrogen atom. In a different organism, C. albicans, a similar set of amino acids were found to be essential to the catalytic activity, respectively the Glu88-Asp-89-Ile90 system, Asp125 and Tyr133. Structure As of late 2019, 13 structures have been solved for this class of enzymes in different species, with PDB access codes