Glutamate reactions

To achieve its catalytic reaction, glutamate mutase faces the problem of how to surmount the two relatively high transition-state energy barriers that lead from the 4-glutamyl radical to acrylate and the glycyl radical and then the recombination of these radicals to the 3-methylene-aspartate radical (Scheme 4). These barriers were computed as AH = -f 59.9 and - - 66.5 kJ mol (10), respectively, and the 3-methylene-aspartate radical was found to be significantly less stable than the resonance-stabilized 4-glutamyl radical (AH = 20.3 kJ mol ). Likewise, with methylmalonyl-CoA mu-... 

In the backward reaction, glutamate dehydrogenase provides an oxidizable carbon source used for the production of energy. 

Proline. Proline catabolism begins with an oxidation reaction that produces A -pyrroline. The latter molecule is converted to glutamate-y-semialdehyde by a hydration reaction. Glutamate is then formed by another oxidation reaction. 

NADPH-GltS and Fd-GltS also catalyze the reverse reaction - glutamate oxidation forming ammonia and... 

In muscle and brain, but not in liver, the purine nucleotide cycle allows Nlij to be released from amino acids (see Fig. 38.5). Nitrogen is collected by glutamate from other amino acids by means of transamination reactions. Glutamate then transfers its amino group to oxaloacetate to form aspartate, which supplies nitrogen to the purine nucleotide cycle (see Chapter 41). The reactions of the cycle release fumarate and NH4. The ammonium ion formed can leave the muscle in the form of glutamine. 

The available evidence indicates that in brewing yeast the main acceptor for amino groups is a-oxoglutarate [61]. The products of the reaction, glutamic acid and an oxo-acid (the carbon skeleton of the amino acid) enter the cell s metabolic pools. The synthesis of amino acids by the yeast cell then proceeds by transfer of the amino group of glutamic acid to oxo-acids in the pools. The oxo-acids may be derived from amino acids present in wort or from carbohydrate metabolism. In the latter instance, de novo synthesis of amino acids is said to occur and the penultimate reaction is usually transamination [see Fig. 17.16]. 

Glutamine is formed by the enzyme glutamine synthase, which catalyses the reaction Glutamate + ATP + Glutamine + ADP + Pj... 

A transimination reaction with a lysine side chain releases the product of the reaction (glutamate) and regenerates the imine between PLP and the lysine side chain of the enzyme. 

Figure 10.3-20 shows that i-glutamate plays an important role in the metabolism with many reactions leading to this compound and many reactions starting from it. The first example gives a full structure search in order to show how easy it is to find all reactions that a certain compound participates in. 

The 20 ammo acids listed m Table 27 1 are biosynthesized by a number of different path ways and we will touch on only a few of them m an introductory way We will exam me the biosynthesis of glutamic acid first because it illustrates a biochemical process analogous to a reaction we discussed earlier m the context of amine synthesis reductive ammatwn (Section 22 10)... 

Abass and colleagues developed an amperometric biosensor for NHA that uses the enzyme glutamate dehydrogenase to catalyze the following reaction. 

The reaction is very slow in neutral solution, but the equiUbrium shifts toward the lactam rather than glutamic acid. Under strongly acidic or alkaline conditions, the ring-opening reaction requires a very short time (10). Therefore, neutralization of L-glutamic acid should be performed cautiously because intramolecular dehydration is noticeable even below 190°C. 

The first L-folic acid synthesis was based on the concept of a thiee-component, one-pot reaction (7,22). Ttiainino-4(3JT)-pyrirnidinone [1004-45-7] (10) was reacted simultaneously with C -dibromo aldehyde [5221-17-0] (11) and j )-aminoben2oyl-L-glutamic acid [4271-30-1] (12) to yield fohc acid (1). 

Radiolabeled folate provides a powerful tool for folate bioavaHabiUty studies in animals and for diagnostic procedures in humans. Deuteration at the 3- and 5-positions of the central benzene ring of foHc acid (31) was accompHshed by catalytic debromination (47,48) or acid-cataly2ed exchange reaction (49). Alternatively, deuterium-labeled fohc acid (32) was prepared by condensing pteroic acid with commercially available labeled glutamic acid (50). 

Folic acid is synthesized both in microorganisms and in plants. Guanosine-5-ttiphosphate (GTP) (33), -aminobenzoic acid (PABA), and L-glutamic acid are the precursors. Reviews are available for details (63,64). The sequence of reactions responsible for the enzymatic conversion of GTP to 7,8-dihydrofohc acid (2) is shown. 

In E. coli GTP cyclohydrolase catalyzes the conversion of GTP (33) into 7,8-dihydroneoptetin triphosphate (34) via a three-step sequence. Hydrolysis of the triphosphate group of (34) is achieved by a nonspecific pyrophosphatase to afford dihydroneopterin (35) (65). The free alcohol (36) is obtained by the removal of residual phosphate by an unknown phosphomonoesterase. The dihydroneoptetin undergoes a retro-aldol reaction with the elimination of a hydroxy acetaldehyde moiety. Addition of a pyrophosphate group affords hydroxymethyl-7,8-dihydroptetin pyrophosphate (37). Dihydropteroate synthase catalyzes the condensation of hydroxymethyl-7,8-dihydropteroate pyrophosphate with PABA to furnish 7,8-dihydropteroate (38). Finally, L-glutamic acid is condensed with 7,8-dihydropteroate in the presence of dihydrofolate synthetase. 

Work in the mid-1970s demonstrated that the vitamin K-dependent step in prothrombin synthesis was the conversion of glutamyl residues to y-carboxyglutamyl residues. Subsequent studies more cleady defined the role of vitamin K in this conversion and have led to the current theory that the vitamin K-dependent carboxylation reaction is essentially a two-step process which first involves generation of a carbanion at the y-position of the glutamyl (Gla) residue. This event is coupled with the epoxidation of the reduced form of vitamin K and in a subsequent step, the carbanion is carboxylated (77—80). Studies have provided thermochemical confirmation for the mechanism of vitamin K and have shown the oxidation of vitamin KH2 (15) can produce a base of sufficient strength to deprotonate the y-position of the glutamate (81—83). 

The side chains of the 20 different amino acids listed in Panel 1.1 (pp. 6-7) have very different chemical properties and are utilized for a wide variety of biological functions. However, their chemical versatility is not unlimited, and for some functions metal atoms are more suitable and more efficient. Electron-transfer reactions are an important example. Fortunately the side chains of histidine, cysteine, aspartic acid, and glutamic acid are excellent metal ligands, and a fairly large number of proteins have recruited metal atoms as intrinsic parts of their structures among the frequently used metals are iron, zinc, magnesium, and calcium. Several metallo proteins are discussed in detail in later chapters and it suffices here to mention briefly a few examples of iron and zinc proteins. 

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