Glucosamine 6-phosphate, biosynthesis

Several different pathways can be envisioned for the conversion of DHQ into AB. One such pathway (Figure 8) has some of the same chemical features as the shikimate pathway but begins with a 4-amino analogue of DHQ The critical first step in the pathway may proceed in a manner similar to that seen in glucosamine-6-phosphate biosynthesis, in which an a-hydroxyaldehyde is converted into an a-aminoaldehyde." " It is possible that the reduction of the ketone (step 3, Figure 8) could be performed by the normal shikimate enzyme, provided it could function with the 4-amino-containing analogue. Step 4 could occur either by loss of water or by phosphorylation followed by the loss of phosphate as occurs in the shikimate pathway. The last compound in this pathway, rrtf j -4-amino-3-hydroxy-l,5-cyclohexadiene-l-carboxylic acid, has been prepared" " and we have now shown it to be a precursor to pAB. 

In the biosynthesis of A. s., the amino group is supplied by transamination from glutamine. Fructose 6-phosphate is aminated to D-glucosamine 6-phosphate by a hexose-phosphate transaminase. Glucosamine phosphate can then be converted by a transacetylase into the N-acetyl derivative. The latter is isomerized to the 1-phosphate, then activated by reaction with UTP, to form UDP-N-acetylglucosamine, which can be isomerized to UDP-N-acetylgalactosamine. See Muramic acid. Neuraminic acid. 

Chlorotetaine is an irreversible inhibitor of glucosamine-6-phosphate synthetase and thereby interferes with ceil wall biosynthesis. The terminal steps of a synthesis of Chlorotetaine are shown in Scheme 6.15 in which deprotection of an iV-terminal amino group is a prelude to the final enzymatic hydrolysis of a methyl ester function.43 Critical to the success of the synthesis was the suppression of easy racemisation at the ring juncture in the ester hydrolysis step by using porcine pancreatic lipase. 

See also Fructose, Biosynthesis of Amino Sugars, Fructose Metabolism, Glucosamine-6-Phosphate... 

See also Biosynthesis of Glycoconjugates, Chitin, Glucosamine-6-Phosphate, Bacterial Cell Walls... 

Figure 16.13 Pathway for biosynthesis of UDP-N-acetylglucosamine from glucosamine-6-phosphate. 

Glucosamine is recovered as A -acetylglucosamine-6-phosphate and the reacetylation probably follows phosphorylation, as in the normal biosynthesis of A -acetylhexosamine phosphates from fructose-6-phosphate. In practice, most reclamation is probably at the level of liberated A/-acetylhexosamine, rather than hexosamine. 

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