Glutamine hexosamine

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. 

L-Glutamine donates nitrogen for hexosamine synthesis in Neurospora crassa and for the n-glucosamine units of hyaluronate in streptococci. Of twenty-three amino acids (and ammonium chloride) tested with group A streptococci, L-glutamine was the only consistent nitrogen-donor for... 

The place of L-glutamine in hyaluronate synthesis is shown by experiments with methionine sulfoxide. Since methionine sulfoxide (2-amino-4-methylsulfinylbutyric acid) inhibits L-glutamine formation the addition of the sulfoxide to a culture of hemolytic streptococci inhibits hexosamine synthesis and, consequently, hyaluronate formation. This inhibition can take place at concentrations of methionine sulfoxide which are low enough not to inhibit hyaluronate synthesis with L-glutamine. ... 

Adenosine-5-triphosphoric acid, magnesium sulfate, and cysteine bring about L-glutamine formation from ammonium L-glutamate. However, significant hexosamine synthesis is not observed when these three substances are incubated with ammonium L-glutamate in the presence of a residue-free supernatant from crushed, bacterial cells. L-Glutamine stimu-... 

R.R. Traxinger and S. Marshall, J. Biol. Chem., 1991, 266, 10148 10154, Coordinated Regulation of Glutamine Fructose-6-Phosphate Amidotransferase Activity by Insulin, Glucose, and Glutamine Role of Hexosamine Biosynthesis in Enzyme Regulation. 

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. 

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