Glutamic acid oxidative deamination

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. 

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. 

B. Glutamate dehydrogenase the oxidative deamination of amino acids... 

Alanine, aspartate, and glutamate are synthesized by transfer of an amino group to the a-keto acids pyruvate, oxaloacetate, and a-keto-glutarate, respectively. These transamination reactions (Figure 20.12, and see p. 248) are the most direct of the biosynthetic pathways. Glutamate is unusual in that it can also be synthesized by the reverse of oxidative deamination, catalyzed by glutamate dehydrogenase (see p. 249). 

Nitrogen incorporated into urea in the Ever originates from both intrahepatic and extrahep-atic sources. Urea contains two nitrogen atoms one is derived from ammonium, while the other is derived from aspartic acid. In Ever hepato-cytes, ammonium is generated by the oxidative deamination of glutamic acid, catalyzed by glutamate dehydrogenase,... 

The flavin co-factor is reduced with concomitant oxidation of the amino acid into the corresponding imino acid, which spontaneously hydrolyzes to the a-keto acid and ammonia the flavin co-factor is then reoxidized by molecular oxygen with the production of hydrogen peroxide. Both D- and L-amino acid oxidases deaminate a variety of amino acids, particularly those having a hydrophobic side chain, but are practically inactive on acidic amino acids (which are deaminated by specific glutamate and aspartate oxidases) and are strictly stereospecific. 

Many of the transaminase reactions are linked to the amination of 2-oxo-glutarate to glutamate or glyoxylate to glycine, which are substrates for oxidative deamination, reforming the oxo-acids, and thus providing a pathway for net deamination of most amino acids. 

A biomimetic synthesis of solerone (5-oxo-4-hexanolide) 1 using both enzymatic and acid-catalyzed reactions was performed. Starting from L-glutamic acid 5-ethyl ester 2 enzymatic oxidative deamination followed by subsequent decarboxylation of the corresponding 2-oxoglutaric acid 5-ethyl ester 3 led to ethyl 4-oxobutanoate 4. In the presence of pyruvate,... 

The a-amino group of many amino acids is transferred to a-ketoglutarate to form glutamate, which is then oxidatively deaminated to yield ammonium ion (NH4 +). 

The carbon skeletons of several five-carbon amino acids enter the citric acid cycle at a -ketoglutarate. These amino acids are first converted into gluta-mate, which is then oxidatively deaminated by glutamate dehydrogenase to yield a-ketoglutarate (Figure 23.23). 

Glutamate, which now contains the nitrogen atom of the former amino acid, next undergoes an oxidative deamination to yield ammonium ion and regenerated a-ketoglutarate. The oxidation of the amine to an imine is mechanistically similar to the oxidation of a secondary alcohol to a ketone and is carried out by NAD. The imine is then hydrolyzed in the usual way. ... 

Glutamate dehydrogenase plays a major role in amino acid metabolism. It is a zinc protein, requires NAD+ or NADP+ as coenzyme, and is present in high concentrations in mitochondria of liver, heart, muscle, and kidney. It catalyzes the (reversible) oxidative deamination of L-glutamate to a-ketoglutarate and NH3. The initial step probably involves formation of a-iminoglutarate by dehydrogenation. This step is followed by hydrolysis of the imino acid to a keto acid and NH3 ... 

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