Oxidative Deamination of Amino Acids

The NHg-group of amines and other amino acids may be transferred by transamination (C 5) to x-ketoglutaric acid. Hence most of the ammonia liberated by the degradation of amino acids and amines is formed by glutamic acid dehydrogenase. 

) The Enzymes, Vol. 11, Oxygenation -Electron Transfer. Academic Press. New York 1975 Jeffery, J. (ed.) Dehydrogenases. Birkhauser, Basel 1980 

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

Amino acids are chemically reactive at their a-amino groups and their side chains. The carboxyl groups are relatively unreactive unless activated. A very useful reaction is the oxidative deamination of amino acids with ninhydrin. The reaction produces a blue pigment, which can be used for the detection of amino acids both qualitatively and quantitatively. The series of reactions producing the blue complex is given in Equation (4.2). 

The enzymes discussed in this paragraph are D- and L-amino acid oxidases, the presence of which has been detected in numerous organisms and tissues. They were only recently identified in bacteria and the corresponding enzymes were isolated (for a review see [54]). These enzymes are flavin adenine dinucleotide (FAD)-containing flavoproteins that catalyze the oxidative deamination of amino acids (Scheme 13.21). 

By (often photoinduced) oxidative deamination of amino acids (E (L) = -0.05 V) coordinated to Fe(III), these are converted to 2-oxocarboxylates or glyoxy-late and eventually oxalate (E (L) = -0.17 V)... 

Precipitation of CaC03 is also promoted by ammonia which may be produced by organisms under both aerobic and anaerobic conditions. The most common reaction is oxidative deamination of amino acids which liberates ammonia according to eqn (10) ... 

Ammonia arises in the body principally from the oxidative deamination of amino acids. In addition to its uptake in the reactions mentioned above, ammonia is also excreted in the urine as ammonium salts. This is not derived directly from the blood ammonia but is formed by the kidney from glutamine by the action of glutaminase. In metabolic acidosis, ammonia production and excretion by the kidney is greatly increased, and conversely it is decreased in metabolic alkalosis. This may be an important means of excreting excess ammonia. It must be remembered that ammonia formed by the action of intestinal bacteria on the protein hydrolyzates in the intestine can be also absorbed. The contribution of the ammonia formed in this way to the total ammonia in the body is unknown. Since this ammonia drains into the portal circulation, it is promptly removed by the liver. 

It is difficult to estimate what the rate of the metal ion catalyzed oxidative deamination reaction of amino acids would be in natural waters. Hamilton and Revesz (30) found that the rate of oxidation of alanine in the presence of pyridoxal and manganese ions was inhibited by EDTA. Since metal ions in natural waters can be complexed by a variety of organic and inorganic compounds, their effectiveness in catalyzing the oxidative deamination of amino acids may be reduced. Also, the fraction of dissolved amino acids which would be complexed by metal ions at the pH and metal ion and amino acid concentrations found in natural waters must be considered. At neutral pH, where the amino group of the amino acid is protonated, the fraction of the amino acid that would be in the form of the metal ion complex depends upon the equilibrium constant for the formation of the complex and the pK of the amino proton of the amino acid. The reactions for the formation of the Cu2+-alanine complexes can be written as... 

One of the mechanisms which has been proposed to account for the oxidative deamination of amino acids invokes a transamination followed by a deamination. This mechanism appears to be capable of explaining the rapid and reversible deaminations whose character is not in accordance with the properties and action of the L-amino acid oxidases. A transamination to a-ketoglutaric acid would remove the amino group from an... 

Aldehydes formed by the Strecker degradation (cf. 5.3.1.1 Table 5.16) can also be obtained as metabolic by-products of the enzymatic transamination or oxidative deamination of amino acids. First, the amino acids are converted enzymatically to a-keto acids and then to aldehydes by decarboxylation in a side reaction ... 

Monoaminomonocarboxylic a-amino acids with a primary amino group produce sensory active aldehydes called Strecker aldehydes. Strecker degradation of P-amino acids yields alkan-2-ones known as methylketones (see Section 8.2.4.1.2). By analogy, alkane-3-ones (ethylketones) are formed from y-amino acids. The general reaction is schematically indicated in Figure 2.43. The reaction mechanism, however, varies considerably depending on the type of oxidant and amino acid. 2-Imino acids and 2-oxoacids can in some cases apparently form as intermediates, analogous to enzymatically catalysed transamination and oxidative deamination of amino acids (see Section 2.5.1.3.2). Some Strecker aldehydes readily decompose, such as methional, or yield cyclic products, such as 5-aminopentanal, which dehydrates to 2,3,4,5-tetrahydropyridine. 

Histamine is formed by the enzymic decarboxylation of histidine. It is degraded by diamine oxidase (a flavoprotein) to give the aldehyde and NH3 and thus is inactivated. The reaction is analogous to oxidative deamination of amino acids. 

Most venoms contain a variety of enzymes and most are hydrolytic, with the notable exception of 1-amino acid oxidase, which causes the oxidative deamination of amino acid. The variety of enzymes present in snake venoms is summarized here. 

Strecker Degradation (Oxidative Deamination), Mild oxidizing agents such as aqueous sodium hypochlorite or aqueous A-bromosuccinimide, cause decarboxylation and concurrent deamination of amino acids to give aldehydes. 

The citric acid cycle is not only a pathway for oxidation of two-carbon units—it is also a major pathway for interconversion of metabolites arising from transamination and deamination of amino acids. It also provides the substtates for amino acid synthesis by transamination, as well as for gluconeogenesis and fatty acid synthesis. Because it fimctions in both oxidative and synthetic processes, it is amphibolic (Figure 16—4). 

Glycogenolysis and glycogen synthesis P-oxidation of fatty acids transamination and deamination of amino acids Cori cycle and glucose-alanine cycle, which recycles substrates between muscle and liver. 

Deamination removal of the amino group (-NH ) from a chemical compound (usually an amino acid). MetaboUcally, D. may occur by a) oxidative D. of amino acids to ketoacids and ammonia by Flavin enzymes (see) and pyridine nucleotide enzymes (see Amino acids, Table 3) b) Transamination (see) in which an amino group is transferred fiom an amino to a keto compound, and c) removal of ammonia from a compound, leaving a double bond, e.g. the D. of L-aspartate to marate, and the D. of histidine to urocanic acid. IVansamination is important in the synthesis of amino acids from tricarboxylic acid cycle intermediates the reverse reactions feed excess amino acids into the tricarboxylic acid cycle for oxidation. 

The first stage in the oxidative degradation of amino acids is the removal of the amino group by one of two main pathways, oxidative deamination or transamination. In transamination the amino group is transferred to the a-carbon atom of a keto acid, usually a-ketogjutarate, resulting in the production of another keto acid and glutamate. The reactions are catalysed by enzymes known as aminotransferases. The reaction for aspartate may be represented as ... 

Amino acid oxidase oxidatively deaminates the amino acid at the left (one of many) the enzyme specifically catalyzes this particular reaction as described extensively in Chapt. VIII-7. Another possible reaction, decarboxylation, does not occur. The catalysis of CO2 loss requires a different enzyme, and a third reaction, transamination, requires a third enzyme assisting in the exchange of functional groups (the keto group of oxaloacetic acid with the amino group). Obviously each of the three enzymes possesses a characteristic reaction specificity this is true for all enzymes. 

The flavoprotein amino acid oxidases (AAOs) catalyze an essentially irreversible oxidative deamination of an amino acid. Molecular oxygen is the oxidant and the products are ammonia, the oxoacid, and H2O2 (Equation (1)). 

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. 

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