Glutamate oxidative deamination

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). 

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. 

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). 

B. In the liver, glutamate dehydrogenase catalyzes the oxidative deamination of glutamate to produce free ammonia (Figure 9-1). 

Terms in bold are defined in aminotransferases 660 transaminases 660 transamination 660 pyridoxal phosphate (PLP) 660 oxidative deamination 661 l-glutamate dehydrogenase 661 glutamine synthetase 662 glutaminase 663 creatine kinase 664... 

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

Proline is oxidized to glutamate. Glutamate is transaminated or oxidatively deaminated to form a-ketoglutarate. 

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). 

Glutamate can be oxidatively deaminated in the liver by glutamate dehydrogenase, liberating free ammonia that can be used to make urea. 

The free ammonia formed by oxidative deamination of glutamate is converted into carbamoyl phosphate in a three-step reaction requiring two ATP molecules (fig. 22.8). 

The glutamate produced by transamination is oxidatively deaminated by glutamate dehydrogenase to produce ammonia. This enzyme is unusual in being able to use either NAD+ or NADP+, and is subject to allosteric regulation. GTP and ATP are allosteric inhibitors, whereas GDP and ADP are allosteric activators. 

Carbamoyl phosphate synthetase, which is technically not a member of the urea cycle, catalyzes the condensation and activation of ammonia (from the oxidative deamination of glutamate by glutamate dehydrogenase Topic M2) and C02 (in the form of bicarbonate, HC03 ) to form carbamoyl phosphate. The hydrolysis of two ATP molecules makes this reaction essentially irreversible. 

Glutamate dehydrogenase, which catalyses the oxidative deamination of glutamate,... 

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