Glutamate deamination

A new reaction scheme for the synthesis of 5-aminolevulinic acid, considering the RNA dependent formation of G-l-SA from glutamate, deamination to DOVA and transamination to ALA. 

Although the equilibrium of this reaction is very much in favour of glutamate formation, in the cell the rapid removal of the 2-oxoglutarate and NAD(P)H allows the enzyme to function efficiently in the direction of glutamate deamination. Liver glutamate dehydrogenase is a very active enzyme, and the reaction is not rate-limiting for amino acid deamination. 

Glutamate deamination is the main route of nitrogen removal in the body. Glutamate dehydrogenase is a mitochondrial enzyme in the Hver and the kidney. It can use NADH or NADPH as coen rmes for its catalytic activity. 

Urea biosynthesis occurs in four stages (1) transamination, (2) oxidative deamination of glutamate, (3) ammonia transport, and (4) reactions of the urea cycle (Figure 29-2). 

These points have important functional implications. While neuronal glutamate may come from glucose via pyruvate, the Krebs cycle and transamination of alpha-oxoglutamate, it seems likely that most of the transmitter originates from the deamination of glutamine. After release, the high-affinity uptake sites (transporters)... 

Glutamate is a commonly occurring amino acid that acts as an excitatory transmitter in CNS. The molecule may be synthesized within the nerve ending either by transamination from 2-oxoglutarate (described in Section 6.3.1.1) or by deamination of glutamine (see Section 8.2.2). However, in common with other synaptic signals, there exists an efficient uptake mechanism in the axon to recycle glutamate that has been released. 

Additionally, several amino acids may undergo transamination to produce glutamate which in the liver is oxidatively deaminated to form 2-oxoglutarate (2-OG, see Figure 6.6), a substrate of the TCA cycle. Alternatively, glutamate maybe converted into glutamine, an important but often overlooked fuel substrate. 

The 2-oxoglutarate produced is recycled for transamination or may enter the TCA cycle. The ammonia liberated by oxidative deamination is used to form glutamine (from glutamate, catalysed by glutamine synthase) prior to export from the muscle cell ... 

The glutamate which results form the reaction remains in the mitochondria where it is oxidatively deaminated by glutamate dehydrogenase to form 2-oxoglutarate. 

Most of the applications so far focus on the production of the chiral amino acid as the end product. Conversion of the chiral amino acid into the prochiral oxoacid as the end product is less common, although, for instance, Odman etal describe the use of GDH to convert L-glutamate into the higher-value 2-oxoglutarate. Similarly, Findrik et al describe in some detail the kinetics of quantitative conversion of L-methionine into 2-oxo-4-methylthiobutyric acid. In view of the relatively unfavorable equilibrium for amino acid oxidation, thermodynamic and kinetic considerations have to be carefully balanced. A high pH favors oxidative deamination, and fortunately also the PheDH has an unusually high pH optimum, above 10. However, this in itself will not secure... 

This enzyme is found in many tissues, where it catalyzes the reversible oxidative deamination of the amino acid glutamate. It produces the citric acid cycle intermediate a-ketoglutarate, which serves as an entry point to the cycle for a group of glucogenic amino adds. Its role in urea synthesis and nitrogen removal is stiU controversial, but has heen induded in Figure 1-17-1 and Table 1-17-1. 

Glutamate dehydrogenation is involved in deamination of most of the amino acids. The first two reactions are not involved in the overall deamination system they are included here for completeness and because they are of some general interest. The complete biochemical description of these reactions is given in Appendix 8.4. For a few amino acids, e.g. threonine and serine, other specific reactions are responsible for deamination. 

The amino acid glutamate is deaminated in a reaction catalysed by the enzyme glutamate dehydrogenase, using either NAD+ or NADF as the oxidising agent, as follows ... 

Glutamate dehydrogenase, in combination with the process of transamination, plays the major role in deamination of many amino acids. 

The fate of the glutamate is re-formation of oxoglntarate in the deamination reaction catalysed by glntamate dehydrogenase, in which the NH2 gronp in glntamate is removed as ammonia and the oxoglntarate is formed, as follows ... 

Some amino acids are converted to glutamate prior to deamination these are proline, arginine, histidine and glutamine (Figure 8.12). 

Figure 9.5 A summary of pathways of the three main fueb and the positions where they enter the cycle. The figure also shows the release of hydrogen atoms/electrons and their transfer into the electron transfer chain for generation of ATP and formation of water. Glutamine is converted to glutamate by deamidation and glutamate is converted to oxoglutarate by transamination or deamination. The process of glycolysis also generates ATP as shown in the Figure.

Oxidative deamination, with the formation of NADH+H only applies to glutamate in animal metabolism. The reaction mainly takes place in the liver and releases NH3 for urea formation (see p. 178). 

This enzyme [EC 3.5.3.13] catalyzes the hydrolytic deamination of iV-formimino-L-glutamate to yield iV-formyl-L-glutamate and ammonia. 

Varela et al. have described some stereoregular hydroxylated polymannaramides (91) [93] by reaction of o-mannaro-l,4 6,3-dilactone (90) with even-numbered alkylenediamines (n = 2, 6, 8, 10, 12). Hydroxylated stereoregular and nonstereoregular polyamides were also prepared by the same authors [94] from hexam-ethylene diamine and pentachlorophenyl (25)-5-oxo-2-tetrahydrofurancarboxylate 93, the latter being derived [95] from the chiral (25)-2-hydroxypentanedioic acid 5,2-lactone (92), a compound obtained [96] by deamination of the easily available L-glutamic acid. 

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