L-Glutamine:D-fructose-6-phosphate

L-Glutamine D-fructose 6-phosphate aminotransferase (EC 2.6.1.16) is widely distributed in mammalian tissue,430,431 and in E. coli,4MNeurospora cras a,4S0 and B. subtilis.432,433 The enzyme catalyzes the formation of 2-amino-2-deoxy-D-glucose 6-phosphate ... 

L-Glutamine + D-fructose-6-phosphate - D-gIucosamine-6-phosphate + L-glutamate... 

In several studies of the L-glutamine D-fructose 6-phosphate amidotransferase reaction it has been shown that specific glutamine antagonists may be used to inhibit the reaction. Ghosh et al. (1960) showed that 6-diazo-5-oxo-L-norleucine (DON) was a potent inhibitor of the enzyme, whereas azaserine was less effective. The glutamine analogs, methionine sulfoxide and y-glutamyl hydrazide, on the other hand, were not inhibitory (Clarke and Pasternak, 1962). 

Another, more classical, control mechanism exists for the feedback regulation of key enzymes for the synthesis of Gm-6-P04 and for N-acetylmannosamine. Each of these is the first enzyme in the metabolic commitment to hexosamine and sialic acid synthesis. Komfeld et al, (1964) showed that UDP-GlcNAc is an efficient feedback inhibitor for L-glutamine-D-fructose-6-phosphate aminotransferase and that CMP-NAN also inhibits UDP-GlcNAc-2-epimerase, which is responsible for the synthesis of A/ -acetylmannosamine. This is an example of the by now familar endproduct inhibition of the first enzyme of a metabolic pathway (see Figure 6). They were also able to demonstrate that in vivo administration of puromycin to rats, which inhibits de novo protein synthesis and also depresses sialic acid and hexosamine utilization, does not lead to an accumulation of UDP-GlcNAc. Furthermore, the turnover of the UDP-hexosamine pool was shown to be slowed down. These data suggest that impairment of the utilization of UDP-hexosamine leads to decreased synthesis of UDP-hexosamines or their precursors (i.e., classical feedback inhibition). 

Winterbum and Phelps (1970) have suggested that the L-glutamine-D-fructose-6-phosphate aminotransferase does not display classical feedback kinetic behavior in the presence of UDP-GlcNAc. Furthermore, they suggest that there is a 10-fold excess of enzyme over that necessary for a steady state for hexosamine metabolism. 

Kornfeld, R., 1967, Studies on L-glutamine D-fructose 6-phosphate amidotransferase I. Feedback inhibition by uridine diphosphate-N-acetylglucosamine, J, Biol. Chem. 242 3135-3141. 

D-Fructose 6-phosphate and ammonia interact to produce hexosamine when they are added to a fraction of pig-kidney protein together with catalytic amounts of A -acetyl-n-glucosamine 6-phosphate. Neither L-glutamine nor L-asparagine can replace ammonium sulfate as a nitrogen source in this system, and D-fructose 6-phosphate cannot be replaced by D-fructose, n-xylose, n-glucose, or D-ribose. The presence of N-acetyl-D-glucosamine is also essential for this reaction. 

Figure 13.1 Biosynthetic conversion of D-glucose into some of biologically important monosaccharides. The enzymes involved in these monosaccharide interconversions are transferases and isomerases. Nncleotide phosphoglycoses are synthesized as the glycose donors for biosynthesis of glycans. It is noted that 2-amino-2-deoxysugars (glycosamines) arise from D-fructose-6-phosphate and glutamine by the action of D-fmctose-6-phosphate L-glutamine transamidase with subsequent acetylation by acetyl coenzyme A...

Yki-Jarvinen, H. Vogt, C. Lozzo, P. Pipek, R. Daniels, M.C. Virkamaki, A. Makimattila, S. Mandarine, L. DeFronzo, R.A. McClain, D. Gottschalk, W.K. UDP-N-acetylglucosamine transferase and glutamine Fructose 6-phosphate amidotransferase activities in insulin-sensitive tissues. Diabetologia 1997, 40, 76-81. 

E.D. Crook, J. Zhou, M. Daniels, J.L. Neidigh and D.A. McClain, Diabetes, 1995, 44, 314-320, Regulation of glycogen synthase by glucose, glucosamine, and glutamine fructose-6-phosphate amidotransferase. 

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