Biochemical Foundations of Human Vital Activity - Volkov, N.I., Nesen, E.N. 2000

Biochemical Foundations of Human Vital Activity
Protein Biochemistry
Intracellular Amino Acid Transformation and Urea Synthesis

Amino Acids that are not used directly for Protein Synthesis or are formed during intracellular protein degradation undergo further transformations.

Main reactions of Amino acid METABOLISM

There are several types of amino acid transformation reactions characteristic of intracellular metabolism. These include deamination, Transamination, and decarboxylation.

AMINO ACID DEAMINATION involves the loss of an NH₂ group with The formation of free ammonia and keto acids. Deamination reactions proceed with the participation of deaminase or oxidase Enzymes. In addition to ammonia, deamination produces hydroxy and keto acids. Several types of deamination are distinguished: reductive, hydrolytic, intramolecular, and oxidative. The latter two types predominate in animals and humans.

Oxidative Deamination of amino acids proceeds intensively when cellular energy demand increases, as this reaction is accompanied by energy extraction in the form of high-energy H₂ within reduced NADH₂ or FADH₂. Glutamic acid undergoes oxidative deamination most actively, which is associated with the high activity of Glutamate dehydrogenase found in almost all Tissues:

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The enzyme glutamate dehydrogenase catalyzes both the deamination reaction and the reversible amination reaction, which leads to the formation of glutamic acid from ammonia and α-ketoglutaric acid. This process is called reductive amination.

AMINO ACID TRANSAMINATION is the reaction of transferring an amino group from an amino acid to a keto acid. Such reactions are reversible and are termed transamination. During transamination reactions, new amino and keto acids are formed:    

Currently, more than 60 transamination reactions have been studied. They are catalyzed by complex enzymes called aminotransferases, whose coenzyme is Pyridoxal phosphate (vitamin B₆).

Transamination reactions play a crucial role in the body's Nitrogen metabolism because they produce new acids. These reactions supply the Liver with almost half of the ammonia, which is detoxified via The Urea Cycle and excreted from the body as the end product of nitrogen metabolism.

AMINO ACID DECARBOXYLATION is another pathway of amino acid transformation in tissues, involving the Cleavage of a carboxyl group and the release of carbon dioxide (CO₂). The decarboxylation of monocarboxylic amino acids yields amines and CO₂. A functionally important reaction of this type is the decarboxylation of The amino acid Histidine, leading to the Formation of the tissue hormone histamine:

Decarboxylation reactions are catalyzed by amino acid Decarboxylases, whose coenzyme is also pyridoxal phosphate (vitamin B₆). Amino acid decarboxylation is an irreversible process that results in the formation of biogenic amines characterized by extreme biological activity.

Many Amino Acids and their transformation products can enter the oxidation cycle or The Biosynthesis of other classes of substances (see Chapter 13).

Conversion of Individual Amino Acids into CARBOHYDRATES and Fats

Amino acids have diverse carbon skeletons and specific metabolic pathways. During Catabolism, they can be converted into individual metabolites of The Citric Acid Cycle, pyruvic acid, or acetyl-CoA (Fig. 98). Subsequently, these metabolites can be converted into glucose or into Fatty acids and Ketone Bodies. Amino acids that yield glucose during Gluconeogenesis are termed glucogenic, whereas those that yield fatty acids and ketone bodies are termed ketogenic. Some amino acids are oxidized to the End products of Metabolism, CO₂ and H₂O, with the generation of energy. However, amino acids account for only 10–15% of the body's Energy Requirements.

Fig. 98 Conversion of amino acids and their utilization for the Synthesis of glucose and fatty acids (in frames) — ketogenic acids from which fatty acids and fats can be synthesized; without frames — glucogenic amino acids converted into carbohydrates

Urea is the main end product of PROTEIN AND NUCLEIC acid degradation

During the catabolism of Proteins and Nucleic Acids, particularly during amino acid deamination, free ammonia (NH₃), as well as keto acids and other substances, are formed in body tissues.

Free Ammonia is toxic to The Human Body, especially to the Brain. Its toxicity is associated with potential local pH shifts in certain PARTS OF THE Cell or alterations in cell membrane charge. Therefore, the body possesses several mechanisms for binding and neutralizing free ammonia. The direct binding of ammonia in the tissues where it is produced is carried out with the participation of glutamic and aspartic amino acids, which are converted into amides — glutamine and asparagine. This binding reaction requires ATP energy and is catalyzed by glutamine or asparagine synthetases:

Amides serve as a temporary detoxification form of ammonia. They easily cross cell membranes and transport ammonia to the liver. In the liver, glutamine is readily converted into glutamic acid and free ammonia:

Ammonia delivered to the liver is detoxified through urea synthesis. A portion of free ammonia in Cells is bound during the formation of new amino acids. For instance, oxaloacetate can bind NH₃ to form aspartic acid, which also participates in ammonia detoxification since its amino group is utilized in the urea synthesis pathway.

The process of urea synthesis is a complex enzymatic cycle beginning with a reaction involving the amino acid Ornithine, which is why it is known as the ornithine cycle. The cycle is illustrated in Fig. 99 and consists of 5 main reactions.

The first reaction is the interaction of free ammonia (NH₃) and carbon dioxide (CO₂) molecules involving ATP. This reaction yields high-energy carbamoyl phosphate (1), which subsequently reacts with the amino acid ornithine to form citrulline and phosphoric acid (2). These reactions take place in the Mitochondria. The resulting citrulline is transported from the mitochondria into the Cytoplasm, where it reacts with a molecule of aspartic acid (aspartate), which supplies the second amino group for urea synthesis (3). This reaction consumes ATP energy and produces a complex compound—argininosuccinic acid (argininosuccinate). Argininosuccinic acid is enzymatically cleaved into fumaric acid (fumarate) and Arginine (4). Under the action of the highly specific enzyme arginase, arginine is split into urea and ornithine (5). The newly formed ornithine can then react with a fresh molecule of carbamoyl phosphate, while urea is excreted from the body. The overall equation for urea synthesis is as follows

Fig. 99 Reactions of urea synthesis

Urea is the primary end product of Protein metabolism and other nitrogen-containing substances. Urea excretion accounts for approximately 10–18 g of the human body's total nitrogen, whereas amino acids account for up to 1.15 g, ammonium salts up to 1 g, creatine up to 0.8 g, and uric acid up to 0.2 g. Urea travels from the liver into the bloodstream, then to the Kidneys, and is excreted in the urine.

The normal Blood urea concentration in healthy adults varies individually, ranging from 3.5 to 6.5 mmol ⋅ L^-1 (20–30 mg%). Changes in its blood levels serve as a diagnostic indicator of The rate of tissue protein breakdown. In sports practice, urea is widely used as a biochemical marker to assess recovery processes in the body following physical exertion (see Chapter 24).