Human Biochemistry, Volume 1 - Murray R. 1993

Protein and Amino Acid Metabolism
Catabolism of Amino Acid Nitrogen
Oxidative Deamination

In The Liver and Kidneys of mammals, many Amino Acids undergo oxidative conversion into their corresponding keto acids. Most of the L-a-amino acid activity is driven by the coupled action of transaminases and L-Glutamate dehydrogenase; however, mammalian liver and kidneys also contain L- and D-amino acid oxidases. These oxidases are likewise found in many other animals and microorganisms. Nevertheless, the exact physiological function of L- and D-amino acid oxidases in mammalian Tissues remains somewhat unclear.

Amino acid oxidases are auto-oxidizable Flavoproteins, meaning that reduced FMN or FAD is oxidized directly by molecular oxygen (without the involvement of Cytochromes or other electron carriers) to yield hydrogen peroxide (Н₂О₂) (Fig. 30.5). The toxic product Н₂О₂ is subsequently broken down into О₂ and Н₂О by catalase, an enzyme widely distributed in tissues and especially abundant in the liver. In the absence of catalase, the resulting a-keto acid may undergo non-enzymatic decarboxylation by hydrogen peroxide (Н₂О₂), forming a carboxylic acid with one fewer carbon atom. However, it seems unlikely that such decarboxylation plays any significant role in intact human tissues.

In the Reactions Catalyzed by amino acid oxidases (Fig. 30.5), dehydrogenation mediated by the flavoprotein oxidase occurs first, leading to The formation of an a-imino acid. The latter non-enzymatically adds a Water molecule and is converted into the corresponding a-keto acid, with the loss of the a-amino nitrogen as an ammonium ion.

L-Amino Acid Oxidase, an FMN-containing flavoprotein, is found exclusively in the kidneys and liver of most mammals. Its activity is quite low, and it shows no activity toward Glycine, L-isomers of dicarboxylic amino acids, and ß-hydroxy-a-amino acids. It is doubtful that this enzyme plays a major role in mammalian Amino Acid Catabolism.

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Fig. 30.5. Oxidative Deamination catalyzed by L-amino acid oxidase (L-a-amino acid: oxygen oxidoreductase). The a-imino acid enclosed in parentheses is an unstable intermediate.

In mammals, D-Amino Acid Oxidase is an FAD-containing flavoprotein with a broad substrate Specificity, found in the liver and kidneys of most mammals. D-Asparagine and D-glutamine are not oxidized by this enzyme, whereas glycine and the D-isomers of acidic and basic amino acids serve as poor substrates. The physiological significance of this enzyme in mammals remains unknown.

L-Glutamate Dehydrogenase

The amino groups of Most amino acids are ultimately transferred via Transamination to a-ketoglutarate to form glutamate (Fig. 30.2). The release of the glutamate amino nitrogen as ammonia is catalyzed by L-glutamate dehydrogenase, a highly active enzyme widely distributed in mammalian tissues (Fig. 30.6). Liver glutamate dehydrogenase is a regulatory enzyme; its activity is inhibited by allosteric effectors such as ATP, GTP, and NADH, and stimulated by ADP. Furthermore, glutamate dehydrogenase activity is influenced by certain Hormones.

Glutamate dehydrogenase can utilize either NAD⁺ or NADP⁺ as a cosubstrate. The reaction is reversible and operates in both amino acid catabolism and Biosynthesis. Therefore, its function is not only to channel nitrogen from glutamate into urea synthesis (catabolism) but also to catalyze the reductive amination of a-ketoglutarate by free ammonia (see Chapter 29).

Fig. 30.6. The reaction catalyzed by L-glutamate dehydrogenase. NAD(P)⁺ designates either NAD⁺ or NADP⁺, indicating that both Coenzymes can serve as cosubstrates. The reaction is reversible, but its Equilibrium Constant favors the formation of glutamate.