Amino acids, proteins and peptides are examples of the compounds described below. Many biologically active molecules contain several chemically different functional groups that can interact with each other and with each other's functional groups.
Amino acids.
Amino acids- organic bifunctional compounds, which include a carboxyl group - UNS, and the amino group is N.H. 2 .
Separate α And β - amino acids:
Mostly found in nature α -acids. Proteins contain 19 amino acids and one imino acid ( C 5 H 9NO 2 ):
The simplest amino acid- glycine. The remaining amino acids can be divided into the following main groups:
1) homologues of glycine - alanine, valine, leucine, isoleucine.
Obtaining amino acids.
Chemical properties of amino acids.
Amino acids- these are amphoteric compounds, because contain 2 opposite functional groups - an amino group and a hydroxyl group. Therefore, they react with both acids and alkalis:
Acid-base transformation can be represented as:
The first section of this chapter has already described the need and basic strategy for the breakdown of amino acids. It is explained by the impossibility of storing amino acids for future use and the impossibility of removing them entirely from cells. Excess amino acids are used by organisms as metabolic fuel: their carbon skeletons, during rearrangements of a certain kind, can be involved in the biosynthesis of fatty acids, glucose, ketone bodies, isoprenoids, etc., and can also be oxidized in the TCA cycle, providing the cell with energy. It should be noted that many microorganisms, in particular aerobic bacteria, are able to use individual amino acids as the only source of energy and carbon. In anaerobic microorganisms, in the absence of the tricarboxylic acid cycle in the cells, another mechanism has developed: the catabolism of amino acids in pairs, when one of them serves as an electron donor, and the second as an acceptor. It is important that in this process ATP is formed.
In addition to carbon skeletons, the degradation of amino acids produces amine nitrogen, which, unlike carbon, is not suitable for obtaining energy through oxidation, and moreover, is toxic to cells. Therefore, those amino groups that cannot be reused in biosynthesis are converted into urea (or other substances) and excreted from the body.
Below we will consider the main types of reactions that amino acids can undergo: reactions at the a-amino group, carboxyl group and side chain.
Breakdown of amino acids by amino group . These processes are mainly represented by transamination and deamination reactions at the a-amino group. Transamination reactions have already been discussed in the section on amino acid biosynthesis. They are catalyzed by transaminases (aminotransferases), the distinctive feature of which is the use of pyridoxal phosphate (a derivative of vitamin B 6) as a prosthetic group. Glutamate transaminase and alanine transaminase are of greatest importance in the processes of amino acid degradation. These enzymes act as “funnels” that collect amino groups from different amino acids and incorporate them into glutamate and alanine. In animals, these two amino acids serve as carriers of accumulated amine nitrogen from tissues to the liver. In the liver, the amino group of alanine is transferred by alanine transaminase to a-ketoglutarate to form glutamate:
Thus, most of the amino groups of various amino acids are contained in glutamate, which is easily deaminated.
Deamination reactions of amino acids lead to the release of the NH 2 group in the form of ammonia and are carried out in three different ways. There are oxidative, hydrolytic and direct deamination (Fig. 16.12). The most common type is oxidative deamination, which occurs at the a-amino group and is catalyzed mainly by glutamate dehydrogenase, a typical liver enzyme. An unusual property of this enzyme is its ability to use both NAD and NADP as coenzymes. The activity of glutamate dehydrogenase is regulated by allosteric activators (ADP, GDP) and inhibitors (ATP, GTP).
Oxidative deamination occurs in two steps, producing an imino acid as an intermediate that spontaneously hydrolyzes to form a keto acid and ammonia (Figure 16.12). Both reactions are reversible, and their equilibrium constants are close to unity. Previously (Fig. 16.3) it was shown how, during the reverse reaction, ammonia is included in the composition of glutamate. It can be considered that the reaction of formation and deamination of glutamate is a central reaction in the process of ammonia metabolism.
In many organisms, oxidative deamination is carried out using dehydrogenases that use flavin cofactors (FMN, FAD). These enzymes are called amino acid oxidases. They are characterized by broad substrate specificity: some are specific to L-amino acids, others to their D-analogs. It is believed that these enzymes make a small contribution to the metabolism of amino groups.
Hydrolytic deamination Few amino acids are susceptible, of the proteinogenic ones - asparagine and glutamine. When they are deaminated, aspartate and glutamate are formed, respectively. This process is more correctly called deamidation, since it is carried out by the amide group (Fig. 16.12). In rare cases, the amino group of an amino acid is also split off in this way, then ammonia and hydroxy acid are formed.
As a result direct (intramolecular) deamination unsaturated compounds arise. Histidine, as well as serine, usually undergo direct deamination. However, the initial enzymatic attack of serine results in the elimination of a water molecule (enzyme serine hydratase), and the side hydroxyl group of serine is involved in this conversion. In this case, the unstable intermediate compound, aminoacrylate, undergoes spontaneous deamination. The net reaction product is pyruvate, and this type of deamination is caused by a rearrangement in the amino acid side chain.
Reactions of amino acids at the carboxyl group . Transformations at the carboxyl group of amino acids can be used by organisms to degrade these molecules, as well as to convert them into other compounds necessary for the cell, primarily aminoacyl adenylates and biogenic amines. The formation of aminoacyl adenylates at the preparatory stage of protein synthesis has already been described in Chapter 3. Biogenic amines occur in reactions catalyzed by amino acid decarboxylases. These enzymes are widely distributed in animals, plants, and especially in microorganisms, and it is known that in pathogenic microorganisms decarboxylases can serve factors of aggression, with the help of which the pathogen penetrates into the corresponding tissues. L-amino acid decarboxylases, like transaminases, use pyridoxal phosphate as a prosthetic group.
Monoamines (biogenic amines) perform various functions in organisms. For example, ethanolamine, formed by the decarboxylation of serine, is an integral part of polar lipids. When cysteine and aspartate are decarboxylated, cysteamine and b-alanine are formed, respectively, which are part of such an important coenzyme for cells as coenzyme A. Decarboxylation of histidine leads to the formation of histamine, a mediator involved in the regulation of the rate of metabolic processes, the activity of the endocrine glands, and the regulation of blood pressure in animals. Many other biogenic amines function as signaling substances, particularly those widely distributed in animals and humans. neurotransmitters.
Reactions of amino acids along the side chain . As diverse as the structure of amino acid radicals is, the chemical transformations to which they can undergo are also varied. Among these diverse reactions, we can distinguish those that allow the cell to obtain others from one amino acid. For example, tyrosine is formed by oxidation of the aromatic ring of phenylalanine; hydrolysis of arginine leads to the formation of ornithine (see urea cycle); the breakdown of threonine is accompanied by the formation of glycine, etc.
In addition to these reactions, transformations of side groups associated with the emergence of physiologically active substances are important. Thus, the hormone adrenaline is formed from tyrosine, nicotinic acid (vitamin PP, part of nicotinamide coenzymes) and indolylacetic acid (a growth substance) are formed from tryptophan, and mercapturic acids are formed from cysteine (participate in the neutralization of aromatic compounds). The possibility of converting serine into pyruvate through dehydration of its side chain and deamination has already been noted.
Thus, various chemical transformations of amino acids can lead to the formation of biologically active substances with a wide spectrum of action and, in addition, to the elimination of amino groups in the form of ammonia with the formation of carbon skeletons. The next section will examine the fate of ammonia and the carbon atoms of broken down amino acids.
Amino acids are heterofunctional compounds that necessarily contain two functional groups: an amino group - NH 2 and a carboxyl group - COOH, associated with a hydrocarbon radical. The general formula of the simplest amino acids can be written as follows:
Because amino acids contain two different functional groups that influence each other, the characteristic reactions differ from those of carboxylic acids and amines.
Properties of amino acids
The amino group - NH 2 determines the basic properties of amino acids, since it is capable of attaching a hydrogen cation to itself via a donor-acceptor mechanism due to the presence of a free electron pair at the nitrogen atom.
The -COOH group (carboxyl group) determines the acidic properties of these compounds. Therefore, amino acids are amphoteric organic compounds. They react with alkalis as acids:
With strong acids - like bases - amines:
In addition, the amino group in an amino acid interacts with its carboxyl group, forming an internal salt:
The ionization of amino acid molecules depends on the acidic or alkaline nature of the environment:
Since amino acids in aqueous solutions behave like typical amphoteric compounds, in living organisms they play the role of buffer substances that maintain a certain concentration of hydrogen ions.
Amino acids are colorless crystalline substances that melt and decompose at temperatures above 200 °C. They are soluble in water and insoluble in ether. Depending on the R- radical, they can be sweet, bitter or tasteless.
Amino acids are divided into natural (found in living organisms) and synthetic. Among natural amino acids (about 150), proteinogenic amino acids (about 20) are distinguished, which are part of proteins. They are L-shapes. About half of these amino acids are irreplaceable, because they are not synthesized in the human body. Essential acids are valine, leucine, isoleucine, phenylalanine, lysine, threonine, cysteine, methionine, histidine, tryptophan. These substances enter the human body with food. If their quantity in food is insufficient, the normal development and functioning of the human body is disrupted. In certain diseases, the body is unable to synthesize some other amino acids. Thus, in phenylketonuria, tyrosine is not synthesized. The most important property of amino acids is the ability to enter into molecular condensation with the release of water and the formation of the amide group -NH-CO-, for example:
The high-molecular compounds obtained as a result of this reaction contain a large number of amide fragments and are therefore called polyamides.
These, in addition to the synthetic nylon fiber mentioned above, include, for example, enant, formed during the polycondensation of aminoenanthic acid. Amino acids with amino and carboxyl groups at the ends of the molecules are suitable for producing synthetic fibers.
Alpha amino acid polyamides are called peptides. Depending on the number of amino acid residues, they are distinguished dipeptides, tripeptides, polypeptides. In such compounds, the -NH-CO- groups are called peptide groups.
23.6.1. Decarboxylation of amino acids - cleavage of a carboxyl group from an amino acid to form CO2. The products of amino acid decarboxylation reactions are biogenic amines , involved in the regulation of metabolism and physiological processes in the body (see table 23.1).
Table 23.1
Biogenic amines and their precursors.
The decarboxylation reactions of amino acids and their derivatives are catalyzed by decarboxylase amino acids. Coenzyme - pyridoxal phosphate (vitamin B6 derivative). The reactions are irreversible.
23.6.2. Examples of decarboxylation reactions. Some amino acids undergo direct decarboxylation. Decarboxylation reaction histidine :
Histamine has a powerful vasodilating effect, especially of capillaries at the site of inflammation; stimulates gastric secretion of both pepsin and hydrochloric acid, and is used to study the secretory function of the stomach.
Decarboxylation reaction glutamate :
GABA- inhibitory transmitter in the central nervous system.
A number of amino acids undergo decarboxylation after preliminary oxidation. Hydroxylation product tryptophan converted to serotonin:
Serotonin It is formed mainly in the cells of the central nervous system and has a vasoconstrictor effect. Participates in the regulation of blood pressure, body temperature, respiration, and renal filtration.
Hydroxylation product tyrosine turns into dopamine:
Dopamine serves as a precursor to catecholamines; is an inhibitory type mediator in the central nervous system.
Thiogroup cysteine oxidizes to a sulfo group, the product of this reaction is decarboxylated to form taurine:
Taurine formed mainly in the liver; participates in the synthesis of paired bile acids (taurocholic acid).
21.5.3. Catabolism of biogenic amines. There are special mechanisms in organs and tissues that prevent the accumulation of biogenic amines. The main route of inactivation of biogenic amines - oxidative deamination with the formation of ammonia - is catalyzed by mono- and diamine oxidases.
Monoamine oxidase (MAO)- FAD-containing enzyme - carries out the reaction:
The clinic uses MAO inhibitors (nialamide, pyrazidol) to treat depressive conditions.
The body receives most of its energy from the oxidation of carbohydrates and neutral fats (up to 90%). The rest ~ 10% is due to the oxidation of amino acids. Amino acids are primarily used for protein synthesis. Their oxidation occurs:
1) if the amino acids formed during protein renewal are not used for the synthesis of new proteins;
2) if excess protein enters the body;
3) during periods of fasting or diabetes, when there are no carbohydrates or their absorption is impaired, amino acids are used as an energy source.
In all these situations, amino acids lose their amino groups and are converted into the corresponding α-keto acids, which are then oxidized to CO 2 and H 2 O. Part of this oxidation occurs through the tricarboxylic acid cycle. As a result of deamination and oxidation, pyruvic acid, acetyl-CoA, acetoacetyl-CoA, α-ketoglutaric acid, succinyl-CoA, and fumaric acid are formed. Some amino acids can be converted into glucose, while others can be converted into ketone bodies.
Ways to neutralize ammonia in animal tissues
Ammonia is toxic and its accumulation in the body can cause death. There are the following ways to neutralize ammonia:
1. Synthesis of ammonium salts.
2. Synthesis of amides of dicarboxylic amino acids.
3. Urea synthesis.
The synthesis of ammonium salts occurs to a limited extent in the kidneys, as an additional protective device for the body during acidosis. Ammonia and keto acids are partially used for the resynthesis of amino acids and for the synthesis of other nitrogenous substances. In addition, in kidney tissue, ammonia participates in the process of neutralizing organic and inorganic acids, forming neutral and acidic salts with them:
R – COOH + NH 3 → R – COONH 4 ;
H 2 SO 4 + 2 NH 3 → (NH 4) 2 SO 4;
H 3 PO 4 + NH 3 → NH 4 H 2 PO 4
In this way, the body protects itself from the loss of a significant amount of cations (Na, K, partly Ca, Mg) in the urine during the excretion of acids, which could lead to a sharp decrease in the alkaline reserve of the blood. The amount of ammonium salts excreted in the urine increases markedly with acidosis, since ammonia is used to neutralize the acid. One of the ways to bind and neutralize ammonia is to use it to form the amide bond of glutamine and asparagine. In this case, glutamine is synthesized from glutamic acid under the action of the enzyme glutamine synthetase, and asparagine is synthesized from aspartic acid with the participation of asparagine synthetase:
This way, ammonia is eliminated in many organs (brain, retina, kidneys, liver, muscles). Amides of glutamic and aspartic acids can also be formed when these amino acids are in the protein structure, that is, not only the free amino acid, but also the proteins that contain them can act as an ammonia acceptor. Asparagine and glutamine are delivered to the liver and used in the synthesis of urea. Ammonia is transported to the liver via alanine (glucose-alanine cycle). This cycle ensures the transfer of amino groups from skeletal muscles to the liver, where they are converted into urea, and working muscles receive glucose. In the liver, glucose is synthesized from the carbon skeleton of alanine. In working muscle, glutamic acid is formed from α-ketoglutaric acid, which then transfers the amine group - NH 2 to pyruvic acid, resulting in the synthesis of alanine - a neutral amino acid. Schematically, the indicated cycle looks like this:
Glutamic acid + pyruvic acid ↔
↔ α-ketoglutaric acid + alanine
Rice. 10.1. Glucose-alanine cycle.
This cycle performs two functions: 1) transfers amino groups from skeletal muscles to the liver, where they are converted into urea;
2) provides working muscles with glucose supplied with the blood from the liver, where the carbon skeleton of alanine is used for its formation.
Urea formation– the main route of ammonia neutralization. This process was studied in the laboratory of I.P. Pavlov. It has been shown that urea is synthesized in the liver from ammonia, CO 2 and water.
Urea is excreted in the urine as the main end product of protein and amino acid metabolism. Urea accounts for up to 80-85% of the total urine nitrogen. The main site of urea synthesis in the body is the liver. It has now been proven that urea synthesis occurs in several stages.
Stage 1 - the formation of carbamoyl phosphate occurs in mitochondria under the action of the enzyme carbamoyl phosphate synthetase:
At the next stage, citrulline is synthesized with the participation of ornithine:
Citrulline moves from mitochondria into the cytosol of liver cells. After this, a second amino group is introduced into the cycle in the form of aspartic acid. Condensation of citrulline and aspartic acid molecules occurs to form arginine-succinic acid.
Citrulline aspartic arginine-succinic
acid acid
Arginine-succinic acid is broken down into arginine and fumaric acid.
Under the action of arginase, arginine is hydrolyzed to form urea and ornithine. Subsequently, ornithine enters the mitochondria and can be included in a new cycle of ammonia neutralization, and urea is excreted in the urine.
Thus, in the synthesis of one urea molecule, two molecules of NH 3 and CO 2 (HCO 3) are neutralized, which also plays a role in maintaining pH. For the synthesis of one urea molecule, 3 ATP molecules are consumed, including two in the synthesis of carbamoyl phosphate, one for the formation of arginine-succinic acid; fumaric acid can be converted into malic and oxaloacetic acids (Krebs cycle), and the latter, as a result of transamination or reductive amination, can be converted into aspartic acid. Some of the amino acid nitrogen is excreted from the body as creatinine, which is formed from creatine and creatine phosphate.
Of the total urine nitrogen, urea accounts for up to 80-90%, ammonium salts - 6%. With excess protein feeding, the proportion of urea nitrogen increases, and with insufficient protein feeding it decreases to 60%.
In birds and reptiles, ammonia is neutralized by the formation of uric acid. Poultry manure in poultry farms is a source of nitrogen-containing fertilizer (uric acid).
