Key Reactions

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All animals have the capacity to use or salvage metabolic ammonia in key assimilation reactions involving glutamate dehydrogenase and glutamine synthase. In mammals, assimilation of ammonia also occurs via the action of carbamoyl phosphate synthetase, enabling delivery of carbamoyl phosphate to the urea cycle. The amino group formed by the action of glutamate dehydrogenase may then be transferred to a-keto acids to form a number of important amino acids. This synthesis is catalysed by the aminotransferases or transaminases. Amino acids may also undergo reactions brought about by oxidases and decarboxylases with significant physiological and nutritional consequences. The major sites of amino acid metabolism are gut, muscle, liver, and brain. A summary of some important enzymes involved in amino acid metabolism is presented in Table 4.1.

© CAB International 2003. Amino Acids in Animal Nutrition, 2nd edition (ed. J.P.F. D'Mello)

Fig. 4.1. Overview of pathways in amino acid metabolism in animals.

Table 4.1. Some key enzymes in amino acid metabolism of animals.



Specific examples







Urea cycle enzymes

Uric acid enzymes

Nitric oxide synthases (NOS)

Aspartate aminotransferase Glutamate dehydrogenase D-amino acid oxidases

Tyrosine hydroxyl ase Ornithine decarboxyl ase Orotidylate decarboxyl ase Aromatic decarboxyl ase 5-Hydroxytryptophan decarboxyl ase Ornithine transcarbamoyl ase Argininosuccinate synthetase Argininosuccinase


Glutamine phosphoribosyl pyrophosphate amidotransferase

Phosphoribosyl glycinamide synthetase

Xanthine oxi dase cNOS and iNOS

Synthesis/breakdown of aspartate Synthesis/breakdown of glutamate Conversion of certain D-amino acids to the L-form when linked to an appropriate aminotransferase Formation of Dopa from tyrosine Initiation of polyamine synthesis Pyrimidine biosynthesis Decarboxylation of Dopa Synthesis of 5-hydroxytryptamine Synthesis of citrulline Synthesis of argininosuccinate Breakdown of argininosuccinate to arginine and fu ma rate Breakdown of arginine to urea and ornithine

Incorporation of glutamine in synthesis of purine ring

Incorporation of glycine in purine synthesis

Synthesis of uric acid Synthesis of nitric oxide

Glutamate dehydrogenase

Glutamate dehydrogenase is a key enzyme in amino acid metabolism due to its involvement in both the synthesis of glutamate and its breakdown by the reversible reaction shown below:

a-Ketoglutarate + Ammonia + NAD(P)H+ ■<-► Glutamate + NAD(P)' [4.1]

When linked with aminotransferase reactions, the above pathway enables the synthesis of the non-essential amino acids and the degradation of all amino acids. The breakdown of glutamate by this reaction represents an oxidative deami-nation requiring either NAD+ or NADP+.

Aminotransferases (transaminases)

Aminotransferases or transaminases catalyse the transfer of an amino group from one amino acid (AA) to a keto acid to form another amino acid. These enzymes require pyridoxal phosphate as cofactor to maximize activity. In general terms the aminotransferase reaction may be represented by:

Donor AA + Acceptor a-keto acid -

Product AA + Product a-keto acid [4.2]

Two specific examples are shown below:

Aspartate + a-Ketoglutarate -►

Glutamate + Oxaloacetate [4.3]

Glutamate + Pyruvate -^-Alanine

In theory all aminotransferase reactions should be reversible and this certainly is the case in microbial metabolism, for example in the rumen. However, within animal tissues only a limited number of a-keto acids are readily transaminated to their respective amino acids (Table 4.2).

Using alanine and pyruvate, the two key reactions shown above (Reactions [4.1] and [4.2]) may be rearranged into the following sequence:


Pyruvate a-Ketoglutarati




Urea (mammals) Uric acid (birds)

Urea (mammals) Uric acid (birds)

Table 4.2. «-Keto acids readily transaminated in animal

«-Keto acid

Amino acid







ot-Ketoisocap roate




a-Keto ¡so va le rat e




Glutamine synthase

The assimilation of ammonia may occur by a second pathway catalysed by glutamine synthase as follows:

Carbamoyl phosphate synthetase

The initial step in the degradation of most amino acids involves a transamination reaction which when coupled with the action of glutamate dehydrogenase results in the production of ammonia. The liver is the primary site for coupled reactions of this type, enabling degradation of all amino acids. The ammonia may be re-utilized or, because of its toxicity, converted into urea or uric acid in the liver prior to excretion via the kidneys. Skeletal muscle, however, is the major site for the transamination of the three branched-chain amino acids (BCAA), leucine, isoleucine and valine (Harper et al., 1984). BCAA transaminase accepts all three amino acids as substrates, yielding the respective branched-chain keto acids (BCKA). These keto acids are then transported to the liver for further metabolism. The amino groups of BCAA are eventually used in the synthesis of glutamine which essentially acts as a carrier of ammonia. Species differences have been noted with respect to the initial and ultimate fate of leucine (Seal and Parker, 2000). In non-ruminants, skeletal muscle oxidizes the bulk of leucine derived from muscle protein degradation and the corresponding a-keto acid is re-aminated in the liver. In contrast, in the fasted ruminant, leucine produced from muscle turnover is used in protein synthesis in the liver and gut.

A third mechanism for the assimilation of ammonia involves carbamoyl phosphate synthetase:

Carbamoyl phosphate [4.7]

Carbamoyl phosphate then enters the urea cycle by combining with ornithine, thus enabling the excretion of waste N in mammals. The enzyme, however, is absent in uricotelic animals which consequently lack a functional urea cycle.


In animals only amino acids of the L-configu-ration are encoded for incorporation into tissue proteins. However, D-isomers of certain amino acids may be utilized by animals, following conversion of these isomers to the corresponding L-forms. The enzymes catalysing such reactions are termed D-amino acid oxidases requiring FAD as cofactor. The reaction is shown below:

The a-keto acid then undergoes reaction with an L-specific transaminase to yield the appropriate L-amino acid. This coupled set of reactions enables animals to use D-methionine with up to 90% efficacy (Baker, 1994).


The conversion of glutamate into 7-amino-butyrate (GABA) typifies the physiologically important decarboxylation reactions that lead to the formation of bioactive molecules such as neurotransmitters. The reaction below is catalysed by glutamate decarboxylase, a pyri-doxal phosphate-dependent enzyme:

GABA acts as an inhibitory neurotransmitter in the central nervous system of higher animals. The inactivation of GABA is brought about by the action of GABA-glutamate transaminase resulting in the formation of succinate semialdehyde which is then oxidized to succinate by a specific dehydrogenase (Bradford, 1986).

The synthesis of histamine is also brought about by a decarboxylase. Specifically, histi-dine decarboxylase catalyses the reaction shown below to yield histamine:

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