Glutamate asparagine synthesis

The formation of asparagine from aspartate is chemically analogous to the formation of glutamine from glutamate. Both transformations are amidation reactions and both are driven by the hydrolysis of ATP. The actual reactions are different, however. In bacteria, the reaction for the asparagine synthesis is... 

The non-essential amino acids are alanine, arginine, aspartate, asparagine, cysteine, glutamate, glutamine, glycine, proline, serine and tyrosine. A summary of the reactions involved in their synthesis is given in Figure 8.3 and full details of these pathways are provided in Appendix 8.2. 

Fig. 1.3 Reactions showing synthesis of glutamate in brain. Aspartate aminotransferase (1) glu-taminase (2) glutamate dehydrogenase (3) GABA aminotransferase (4) alanine aminotransferase (5) ornithine aminotransferase (6) Al-pyrroline 5-carboxylic acid dehydrogenase (7) and asparagine synthetase (8)...

Cyclization of aspartic acid and asparagine to form aspartimides, and to a lesser extent of glutamic acid and glutamine to form glutarimide is an acid- and base-catalyzed common side reaction in peptide synthesis (see also Section 2.2.2). In SPPS it is particularly troublesome when Asp-Gly, Asp-Ala, and Asp-Ser sequences are present,but also with Asp-Asn.P P Piperidine-catalyzed aspartimide formation can be very rapid,and in this context DBU is even worse than piperidine.P The formation of aspartimide is reduced by the addition of HOBt or 2,4-dinitrophenol, but more efficiently it is reduced by protecting the aspartyl amide bond with the 2-hydroxy-4-methoxybenzyl (Hmb) group (see Section 2.3.2).P 1... 

Unlike fractions of pig-kidney protein, Neurospora crassa extracts can use L-glutamine, but not ammonium salts nor ammonium salts plus adeno-sine-5-triphosphoric acid. No synthesis of D-glucosamine is stimulated in Neurospora extracts by L-glutamic acid, L-aspartic acid, L-asparagine, L-alanine, glycine, L-valine, L-leucine, L-lysine, L-arginine, L-serine, L-cys-teine, L-citrulline, L-ornithine, butyramide, putrescine, or urea. Recently, a protein fraction has been discovered, in rat liver, that converts D-glucose... 

This amide of glutamic acid has properties similar to those of asparagine. The y-amido nitrogen, derived from ammonia, can be used in the synthesis of purine and pyrimidine nucleotides (Chapter 27), converted to urea in the liver (Chapter 17), or released as NH3 in the kidney tubular epithelial cells. The last reaction, catalyzed by the enzyme glutaminase, functions in acid-base regulation by neutralizing H+ ions in the urine (Chapter 39). 

Fig. I. Metabolic map for synthesis and metabolism of glutamate and aspartate. AAT = aspartate aminotransferase AS = asparagine synthetase GAD = glutamic acid decarboxylase GDH = glutamate dehydrogenase GS = glutamine synthetase OAT = ornithine D-aminotransferase P5CDH = l-pyrroline-5-carboxylate dehydrogena.se PAG = phosphate-activated glutaminase PO = proline oxidase TCA = tricarboxylic acid.

Synthesis and Catabolism of Glutamate, Aspartate, Alanine, Glutamine, and Asparagine (Diagram 1, 2, 3 Figure 20.14)... 

Amino sugars Asparagine Other compounds Glutamate donor for synthesis of Glutathione GABA Ornithine Arginine Proline... 

Dicylohexylcarbodiimide reacts readily with carboxyl groups, as was discussed earlier in regard to its use in peptide synthesis (see text. Section 4.4). Hence, the most likely targets are aspartate and glutamate side chains. In fact, aspartate 61 of subunit C of E. colt Fq is specifically modified by this reagent. Conversion of this aspartate to an asparagine by site-specific mutagenesis also eliminates proton conduction. See A. E. Senior. Biochim. Biophys. Acta 726(1983) 81. 

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