In humans, the main mode of deamination is oxidative deamination. There are two types of oxidative deamination: direct and indirect.
Direct oxidative deamination
Direct deamination is catalyzed by a single enzyme, resulting in the formation of NH 3 and keto acid. Direct oxidative deamination can take place in the presence of oxygen (aerobic) and not require oxygen (anaerobic).
1. Aerobic direct oxidative deamination catalyzed by D-amino acid oxidases ( D-oxidase) as a coenzyme using FAD, and L-amino acid oxidases ( L-oxidase) with coenzyme FMN. In the human body, these enzymes are present, but practically inactive.
Reaction catalyzed by D- and L-amino acid oxidases
2. Anaerobic direct oxidative deamination exists only for glutamic acid, catalyzed only by glutamate dehydrogenase, which converts glutamate to α-ketoglutarate. The enzyme glutamate dehydrogenase is present in the mitochondria of all body cells (except muscle cells). This type of deamination is closely related to amino acids and forms a process with it. transdeamination(see below).
Direct oxidative deamination reaction
glutamic acid
Indirect oxidative deamination (transdeamination)
Indirect oxidative deamination includes 2 stages and is active in all cells of the body.
The first stage consists in the reversible transfer of the NH 2 group from the amino acid to the keto acid with the formation of a new amino acid and a new keto acid with the participation of enzymes aminotransferases. This transfer is called and its mechanism is rather complicated.
As an acceptor keto acid ("keto acid 2") in the body, it is commonly used α-ketoglutaric acid, which turns into glutamate("amino acid 2").
Scheme of the transamination reaction
As a result of transamination, free amino acids lose their α-NH 2 groups and are converted into the corresponding keto acids. Further, their ketoskeleton catabolizes in specific ways and is involved in the tricarboxylic acid cycle and tissue respiration, where it burns down to CO 2 and H 2 O.
When needed (such as starvation), the carbon skeleton of glucogenic amino acids can be used in the liver to synthesize glucose in gluconeogenesis. In this case, the number of aminotransferases in the hepatocyte increases under the influence of glucocorticoids.
The second stage consists in the cleavage of the amino group from amino acid 2 - deamination.
Because in the body, the collector of all amino acid amino groups is glutamic acid, then only it undergoes oxidative deamination with the formation of ammonia and α-ketoglutaric acid. This stage is carried out glutamate dehydrogenase, which is present in the mitochondria of all cells of the body, except for muscle cells.
Given the close relationship between both stages, indirect oxidative deamination is called transdeamination.
Scheme of both stages of transdeamination
If the direct deamination reaction occurs in the mitochondria of the liver, ammonia is used to synthesize urea, which is subsequently removed in the urine. In the tubular epithelium of the kidneys, a reaction is required to remove ammonia through the process of ammonium genesis.
Since NADH is used in the respiratory chain and α-ketoglutarate is involved in the TCA reactions, the reaction is activated when there is an energy deficit and is inhibited. excess ATP and NADH.
Role of transamination and transdeamination
Reactions transamination:
- are activated in the liver, muscles and other organs when an excess amount of certain amino acids enters the cell - in order to optimize their ratio,
- provide the synthesis of nonessential amino acids in the cell in the presence of their carbon skeleton (keto analogue),
- begin when the use of amino acids for the synthesis of nitrogen-containing compounds (proteins, creatine, phospholipids, purine and pyrimidine bases) is stopped - with the aim of further catabolism of their nitrogen-free residue and energy production,
- necessary during intracellular starvation, for example, during hypoglycemia of various origins - for the use of a nitrogen-free amino acid residue in liver for
Redox processes occurring with the participation of amino acids.
These processes take place in plants and animals. There are compounds that can either release hydrogen or absorb it (attach). In biological oxidation, two hydrogen atoms are split off, and in biological reduction, two hydrogen atoms are added. Consider this with the example of cysteine and cystine.
HS NH 2 OH -2H S NH 2 OH
HS NH 2 OH +2H S NH 2 OH
CH 2 - CH - C \u003d O CH 2 - CH - C \u003d O
cysteine cystine
reduced form oxidized form
Two molecules of cystine, losing two hydrogen atoms, form an oxidized form - cysteine. This process is reversible, when two hydrogen atoms are attached to cystine, cysteine is formed - the reduced form. The redox process proceeds similarly on the example of the tripeptide - glutathione, which consists of three amino acids: glutamic, glycine and cysteine.
O \u003d C - NH - CH - CH 2 - SHO \u003d C - NH - CH - CH 2 - S - S -CH 2 - CH - NH - C \u003d O
CH 2 C \u003d O -2H CH 2 C \u003d O C \u003d O CH 2
CH 2 NH +2H CH 2 NH NH CH 2
CH - NH 2 CH 2 glycine CH - NH 2 CH 2 CH 2 CH - NH 2
C = O C = O C = O C = O C = O C = O
OH OH OH OH OH OH
(2 molecules)
tripeptide reduced form hexapeptide - oxidized form
During oxidation, 2 hydrogen atoms are split off and two glutathione molecules are combined and the tripeptide turns into a hexapeptide, that is, it is oxidized.
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Most of the body's energy comes from the oxidation of carbohydrates and neutral fats (up to 90%). The rest ~ 10% due to the oxidation of amino acids. Amino acids are primarily used for protein synthesis. Oxidation occurs:
1) if the amino acids formed during the renewal of proteins are not used for the synthesis of new proteins;
2) if an excess of protein enters the body;
3) during 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, fumaric acid are formed. Some amino acids can be converted to glucose and others to ketone bodies.
Ways to neutralize ammonia in animal tissues
Ammonia is toxic and accumulation in the body can lead to death. There are the following ways to neutralize ammonia:
1. Synthesis of ammonium salts.
2. Synthesis of amides of dicarboxylic amino acids.
3. Synthesis of urea.
The synthesis of ammonium salts occurs to a limited extent in the kidneys, this is like an additional protective device of the body in case of acidosis. Ammonia and keto acids are partly used for the resynthesis of amino acids and for the synthesis of other nitrogenous substances. In addition, in the tissues of the kidneys, ammonia is involved 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 in acidosis, since ammonia is used to neutralize the acid. One of the ways to bind and detoxify ammonia is to use it to form an amide bond between glutamine and asparagine. At the same time, 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:
In 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 a free amino acid can be an ammonia acceptor, but also the proteins in which they are included. Asparagine and glutamine are delivered to the liver and used in the synthesis of urea. Ammonia is transported to the liver and with the help of alanine (glucose-alanine cycle). This cycle ensures the transfer of amino groups from skeletal muscle to the liver, where they are converted into urea, and the working muscles receive glucose. In the liver, glucose is synthesized from the carbon skeleton of alanine. In a working muscle, glutamic acid is formed from α-ketoglutaric acid, which then transfers the amine group - NH 2 to pyruvic acid, as a result, alanine, a neutral amino acid, is synthesized. 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 coming from the blood from the liver, where the carbon skeleton of alanine is used for its formation.
Urea formation- the main way to neutralize ammonia. This process was studied in the laboratory of IP 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, respectively amino acid metabolism. Urea accounts for up to 80-85% of all urine nitrogen. The main site of urea synthesis in the body is the liver. It has now been proven that the synthesis of urea 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 passes from mitochondria to the cytosol of liver cells. After that, a second amino group is introduced into the cycle in the form of aspartic acid. There is a condensation of molecules of citrulline and aspartic acid with the formation of 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, urea and ornithine are formed. Subsequently, ornithine enters the mitochondria and can be included in a new cycle of ammonia detoxification, and urea is excreted in the urine.
Thus, in the synthesis of one molecule of urea, two molecules of NH 3 and CO 2 (HCO 3) are neutralized, which is also important in maintaining pH. For the synthesis of one molecule of urea, 3 ATP molecules are consumed, including two in the synthesis of carbomoyl phosphate, one for the formation of arginine-succinic acid; fumaric acid can be converted to malic and oxaloacetic acids (Krebs cycle), and the latter, as a result of transamination or reductive amination, can be converted to aspartic acid. Some of the amino acid nitrogen is excreted from the body in the form of 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).
23.6.1. Decarboxylation of amino acids - cleavage of the carboxyl group from the amino acid with the formation of 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.
Decarboxylation reactions of amino acids and their derivatives catalyze decarboxylases amino acids. Coenzyme - pyridoxal phosphate (derivative of vitamin B6). The reactions are irreversible.
23.6.2. Examples of decarboxylation reactions. Some amino acids are directly decarboxylated. Decarboxylation reaction histidine :
Histamine has a powerful vasodilating effect, especially capillaries in the focus 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- an inhibitory neurotransmitter 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, has a vasoconstrictive effect. Participates in the regulation of blood pressure, body temperature, respiration, renal filtration.
Hydroxylation product tyrosine goes into dopamine
Dopamine serves as a precursor of catecholamines; is an inhibitory mediator in the central nervous system.
Thiogroup cysteine oxidized 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 way 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 (nialamid, pyrazidol) for the treatment of depression.
The process of splitting off the carboxyl group of amino acids in the form of CO 2 is called decarboxylation. Despite the limited range of amino acids and their derivatives that undergo decarboxylation in animal tissues, the resulting reaction products are biogenic amines- have a strong pharmacological effect on many physiological functions of humans and animals. In animal tissues, decarboxylation of the following amino acids and their derivatives has been established: tyrosine, tryptophan, 5-hydroxytryptophan, valine, serine, histidine, glutamic and γ-hydroxyglutamic acids, 3,4-dioxyphenylalanine, cysteine, arginine, ornithine, S- adenosylmethionine and α-aminomalonic acid. In addition, decarboxylation of a number of other amino acids has been discovered in microorganisms and plants.
In living organisms, 4 types of decarboxylation of amino acids have been discovered:
1. α-Decarboxylation, characteristic of animal tissues, in which the carboxyl group adjacent to the α-carbon atom is cleaved off from amino acids. The reaction products are CO 2 and biogenic amines:
2. ω-decarboxylation characteristic of microorganisms. For example, α-alanine is formed from aspartic acid in this way:
This reaction produces an aldehyde and a new amino acid corresponding to the original keto acid.
This reaction in animal tissues is carried out during the synthesis of δ-aminolevulinic acid from glycine and succinyl-CoA and during the synthesis of sphingolipids, as well as in plants during the synthesis of biotin.
Decarboxylation reactions, unlike other processes of intermediate amino acid metabolism, are irreversible. They are catalyzed by specific enzymes - amino acid decarboxylases, which differ from α-keto acid decarboxylases both in the protein component and in the nature of the coenzyme. Amino acid decarboxylases consist of a protein part, which provides specificity of action, and a prosthetic group, represented by pyridoxal phosphate (PP), as in transaminases.
The mechanism of the amino acid decarboxylation reaction, in accordance with the general theory of pyridoxal catalysis, is reduced to the formation of a PF-substrate complex, represented, as in transamination reactions, by the Schiff base of PF and amino acids: 
Reactions on the carboxyl group:
In living organisms, this reaction proceeds under the influence of enzymes decarboxylases:
Deamination:
Possible hydrolytic deamination of amino acids:
Reductive deamination is characteristic of some organisms:
Squirrels. Primary page. Biological significance of the amino sequence. Deciphering the primary str-ry proteins. Structural levels in architecture and prostr-th organization of proteins. Classification of proteins according to their spatial structure.
Squirrels- it's tall. compounds (polypeptides), the molecules of which are represented by 20 alpha - am-acids, compounds by peptide bonds - CO - NH
Essence: Prost. squirrels- composed of one amino-t. For example, growing proteins - prolamins, blood proteins. plasma - albulins and globulins. Complicated squirrels- in addition to amino acids, they are in St. comp. other org-e compounds (nucleic acids, lipids, carbohydrates), compounds of phosphorus, metals. Them. complicated names nucleoproteins, glycoproteins, etc.
Protozoa amino acid - glycine NH 2 - CH 2 - COOH.
But different. am acids can contain various radicals CH 3 - CHNH 2 -COOH-H - O - - CH 2 - CHNH 2 - COOH
Structure of proteins. Obr-e linear mol-l proteins occurs as a result of those compounds am-acids with each other. Carbox. the group of one am-acid approaches the amino group of the other, and when water is removed, a strong forge occurs between the amino acid residues. connection, name peptide.
Under the primary str-swarm, we mean the order, the sequence of the amino acid residues in the polypeptide chain. To the real time to decipher the primary structure of tens of thousands of different proteins (insulin (51 amino acid residues), human myoglobin (153 amino acid residues), human hemoglobin, cytochrome C from human heart muscle (104), human milk lysozyme (130), bovine chymotrypsinogen ( 245) and many other proteins, including enzymes and toxins.If the protein contains several polypeptide chains that combine into one protein mole through disulf. bonds and non-forging interaction, or if Since one polypeptide chain has internal disulfide bonds, the task of determining the primary structure is somewhat more complicated, since the preliminary separation of these chains and bonds is necessary.
1. Primary. str-ra proteins is unique and determined genetically. Each individual homogeneous protein has a unique sequence of amino acids: the frequency of amino acid replacement is a drive. not only to structural changes, but also to changes in physical and chemical. sv-in and biol-x functions.
2. The stability of the primary structure is provided in the main. peptide bonds; perhaps the participation of a small number of disulf. connections.
3. Various combinations of amino acids can be found in the polypeptide chain; in polypeptides, recurring sequences are relatively rare.
4. In some enzymes, the region near the catalytic St. mi, there are identical peptide str-ry, containing immutable sites and variable sequences of amino acids, esp. in the regions of their active centers. This principle of structural similarity Naib. typical for a number of proteolytic enzymes: trypsin, chymotrypsin, etc.
5. In the primary structure of the polypeptide chain, the determinants are secondary., Tertiary. and quaternary str-ry protein mol-ly, determining its overall spatial conformation.
