Biochemistry and Molecular Biology - Belyasova N.A. 2002

Metabolism. Processes Requiring Energy Input
Metabolism of Nitrogen-Containing Compounds
Amino Acid Breakdown

The first section of this chapter has already outlined the necessity and general strategy of amino acid degradation. This is driven by the inability of Cells to store excess Amino Acids or excrete them intact. Organisms utilize surplus Amino acids as metabolic fuel: their carbon skeletons can undergo specific rearrangements to participate in the Biosynthesis of Fatty acids, glucose, Ketone Bodies, Isoprenoids, and other molecules, or they can be oxidized in the TCA cycle to supply The Cell with energy. It is worth noting that many microorganisms, particularly aerobic Bacteria, are capable of using individual amino acids as their sole source of energy and carbon. In anaerobic microorganisms, which lack a Tricarboxylic Acid Cycle, an alternative mechanism has evolved: the Catabolism of amino acids in pairs, where one acts as an electron donor and the other as an electron acceptor. Crucially, ATP is generated during this process.

In addition to carbon skeletons, amino acid degradation yields amino nitrogen. Unlike carbon, amino nitrogen cannot be oxidized to yield energy and, furthermore, is toxic to cells. Consequently, any amino groups that cannot be reused in biosynthesis are converted into urea (or Other Compounds) and excreted from the Organism.

The primary types of reactions involving amino acids will be examined below: reactions occurring at the a-amino group, the carboxyl group, and the side chain.

Amino acid degradation via the amino group. These processes are primarily represented by Transamination and deamination Reactions Involving the a-amino group. Transamination reactions were already discussed in the section on Amino acid biosynthesis. They are catalyzed by transaminases (aminotransferases), which are distinguished by their use of Pyridoxal phosphate (a derivative of vitamin B₆) as a prosthetic group. Glutamate transaminase and Alanine transaminase play The most significant roles in amino acid degradation. These Enzymes act as "funnels," collecting amino groups from various Amino Acids and incorporating them into glutamate and alanine. In animals, these Two amino acids serve as carriers, transporting accumulated amino nitrogen from Tissues to the Liver. In the liver, the amino group of alanine is transferred by alanine transaminase to a-ketoglutarate, yielding glutamate:

Class="center">Alanine + a-Ketoglutarate → Pyruvate + Glutamate

Thus, the majority of amino groups from various amino acids end up in glutamate, which readily undergoes deamination.

AMINO ACID DEAMINATION reactions result in the release of the NH₂ group as ammonia and proceed via three distinct pathways: oxidative, hydrolytic, and direct deamination (Fig. 16.12). Oxidative Deamination is the most prevalent type; it occurs at the a-amino group and is catalyzed primarily by Glutamate dehydrogenase, a classic liver enzyme. An unusual feature of this enzyme is its ability to utilize both NAD and NADP as Coenzymes. The activity of glutamate dehydrogenase is regulated by allosteric activators (ADP, GDP) and inhibitors (ATP, GTP).

Oxidative deamination takes place in two stages, yielding an imino acid as an intermediate product that spontaneously hydrolyzes to form a keto acid and ammonia (Fig. 16.12). Both reactions are reversible, and their equilibrium constants are close to unity. As shown previously (Fig. 16.3), ammonia is incorporated into glutamate via the reverse reaction. Consequently, the formation and deamination of glutamate can be considered the central pathway in Ammonia METABOLISM.

Fig. 16.12. Various types of amino acid reactions involving the amino group

In many organisms, oxidative deamination is mediated by dehydrogenases that utilize flavin Cofactors (FMN, FAD). These enzymes are referred to as amino acid oxidases. They exhibit broad substrate Specificity: some are specific to L-amino acids, while others are specific to their D-counterparts. These enzymes are thought to play a minor role in Amino Group Metabolism.

Only a few amino acids undergo hydrolytic deamination, namely the Proteinogenic Amino Acids asparagine and glutamine, which yield aspartate and glutamate, respectively. This process is more accurately termed deamidation, as it involves the amide group (Fig. 16.12). In rare cases, the a-amino group of an amino acid is cleaved in this manner, resulting in The formation of ammonia and a hydroxy acid.

Direct (intramolecular) deamination yields unsaturated compounds. Histidine and Serine typically undergo direct deamination. However, the initial enzymatic attack on serine results in the elimination of a Water molecule (catalyzed by serine dehydratase), a process involving the side-chain hydroxyl group of serine. In this case, the resulting unstable intermediate—aminoacrylate—undergoes spontaneous deamination. The net reaction product is pyruvate, and this type of deamination is driven by a rearrangement in The amino acid side chain.

Amino acid reactions involving the carboxyl group. Modifications at the carboxyl group can be utilized by organisms for the degradation of these molecules as well as for their conversion into other compounds essential to the cell, primarily aminoacyl adenylates and biogenic amines. The formation of aminoacyl adenylates during the preliminary stage of Protein Synthesis was described in Chapter 3. Biogenic amines are produced via Reactions Catalyzed by amino acid Decarboxylases. These enzymes are widespread in animals, plants, and particularly microorganisms. Notably, in pathogenic microorganisms, decarboxylases can act as virulence factors that facilitate the invasion of host tissues. Like transaminases, L-amino acid decarboxylases utilize Pyridoxal phosphate as a prosthetic group.

Monoamines (biogenic amines) perform diverse Functions in living organisms. For instance, ethanolamine, produced by the decarboxylation of serine, is an essential component of polar Lipids. The decarboxylation of Cysteine and aspartate yields cysteamine and ß-alanine, respectively, which are Building Blocks of coenzyme A, a crucial cofactor for cellular metabolism. Histidine decarboxylation produces histamine, a mediator involved in regulating metabolic rates, endocrine gland activity, and Blood pressure in animals. Many other biogenic amines function as signaling molecules, notably as widely distributed Neurotransmitters in animals and humans.

Amino acid reactions involving the side chain. The structural diversity of amino acid side chains is matched by the variety of chemical transformations they can undergo. Among these diverse reactions, some enable the cell to synthesize Certain amino acids from others. For example, Tyrosine is formed by The oxidation of the aromatic ring of phenylalanine; the Hydrolysis of Arginine yields Ornithine (cf. The Urea Cycle); and The breakdown of Threonine produces Glycine, among other Examples.

In addition to these reactions, side-chain modifications leading to the synthesis of physiologically active substances are of vital importance. For example, the hormone adrenaline is synthesized from tyrosine; Tryptophan serves as a precursor for nicotinic acid (Vitamin PP, a component of nicotinamide coenzymes) and indoleacetic acid (a plant growth factor); and cysteine gives rise to mercapturic acids (which are involved in the detoxification of Aromatic Compounds). The conversion of serine into pyruvate via side-chain dehydration and deamination has already been noted.

Thus, the diverse Chemical transformations of Amino acids can lead to The production of BIOLOGICALLY ACTIVE SUBSTANCES with a wide spectrum of activity, as well as the release of amino groups as ammonia coupled with the formation of carbon skeletons. The next section will explore the metabolic fate of ammonia and the carbon atoms derived from degraded amino acids.