Catecholamines- a group of hormones synthesized in the adrenal glands by the medulla. The basic group of catecholamines includes: dopamine, adrenaline, norepinephrine. During physical activity and stressful situations, accompanied by a heightened emotional background, the mechanism of hormone synthesis in the blood is triggered.

These hormones help convert fatty acids and glucose into energy and dilate the pupils and bronchioles. Blood vessels constrict, blood pressure increases with the participation of norepinephrine, heart rate increases, blood vessels constrict - adrenaline. After performing their biological function, catecholamines break down into physiologically passive compounds (homovanillic acid, normetanephrine, etc.). The hormones themselves and the elements of their metabolism are excreted from the body by the urinary system. Within the reference values, catecholamines and their processed products are found in the body in low concentrations. Their presence increases noticeably for a short period of time under the influence of stress.

Causes of rising hormone levels
An increase in the content of these hormones may be due to the presence of chromaffin and other neuroendocrine tumors. As a result, the concentration of catecholamines and their breakdown products sharply increases in the urine and blood. The changes may result from a prolonged or short-term increase in blood pressure and, as a rule, the appearance of headaches. Tingling in the arms and legs, trembling, nausea, increased sweating, and anxiety can also be a consequence of increased concentrations of these compounds.

About 90% of chromaffin tumors are localized in the adrenal glands. Mostly, the neoplasms are benign and do not extend beyond the boundaries of the adrenal glands. In the future, it is very likely that their size will increase. In the absence of appropriate therapy, as the tumor grows in size, signs of the disease may become more noticeable and severe. Kidney injury and, moreover, hemorrhage or heart attack, can be a consequence of increased blood pressure caused by chromaffin tumor.

Serotonin
Serotonin is an indicator in the diagnosis of carcinoids (one type of tumor) of the stomach, intestines, and lungs in oncological practice.

Serotonin is formed by decarboxylation of the aromatic amino acid 5-hydroxytryptophan and is a highly active biogenic amine. A significant amount is synthesized by enterochromaffin cells of the gastrointestinal tract. Most of the serotonin is adsorbed by platelets and enters the bloodstream. It is one of the mediators of inflammation. Serotonin has a vasoconstrictor effect. Participates in the regulation of blood pressure, temperature, respiration, renal filtration, and is a mediator of nervous processes in the central nervous system. Serotonin is believed to be involved in the development of allergies, dumping syndrome, toxicosis of pregnancy, carcinoid syndrome and hemorrhagic diathesis. Serotonin is capable of causing platelet aggregation and polymerization of fibrin molecules. It has a stimulating effect on the smooth muscles of blood vessels, intestines, and bronchioles. Serotonin deficiency is believed to underlie functional intestinal obstruction. Its content is increased in metastatic carcinoid tumors of the abdominal cavity in the presence of carcinoid syndrome. In these cases, its concentration increases up to 10 times. After adequate surgical intervention, the level of serotonin in the blood is normalized. In clinical practice, it is used in the diagnosis of carcinoid syndrome (tumors).

Vanillylmandelic acid
VMA (vanillyl mandelic acid) is the main final metabolite of catecholamines, excreted in the urine in large quantities. Measurement of urinary vanillylmandelic acid excretion has historically been considered the main screening test for pheochromocytoma. Determination of VMA or fractionated urinary catecholamines shows higher specificity but less sensitivity than measurement of urinary metanephrines in pheochromocytoma. Comprehensive testing of fractionated catecholamines, their intermediate and final metabolites in urine increases the sensitivity of screening for catecholamine-secreting tumors.

Homovanillic acid
HVA (homovanillic acid) is the main final metabolite of dopamine. The study is used in the diagnosis of catecholamine-secreting tumors, and is important in the diagnosis of neuroblastomas (the information content increases when used in combination with VMA). Used in studies related to the assessment of dopamine metabolism.

5-Hydroxyindoleacetic acid
5-HIAA (5-hydroxyindoleacetic acid) is the main metabolite of serotonin. Measurement of this serotonin metabolite is considered superior to serotonin itself in the diagnosis of abdominal carcinoid tumors. It is also used in a complex of in-depth studies for depression, migraines, monitoring the effectiveness of antidepressant therapy and other conditions associated with changes in the balance of serotonin.

The analysis is carried out for the purpose of diagnosing pheochromocytomas, neuroblastomas and assessing the quality of treatment therapy.

Indications:

• diagnosis and monitoring of catecholamine-secreting tumors - pheochromocytomas, paragangliomas, neuroblastomas;
• differential diagnosis of hypertensive conditions;
• establishing the probable causes of arterial hypertension and hypotension, circulatory failure, heart rhythm disturbances, angina pectoris and myocardial infarction;
• in neurology - studies of neurochemical disorders in parkinsonism (HVA), extrapyramidal hyperkinesis (HVA and VMA), migraine and other cerebrovascular disorders (VMA, HVA and 5-HIAA), hypothalamic syndrome, myoclonic epilepsy (5-HIAA) and seizures of unknown etiology ;
• in psychiatry - study of biochemical changes in mental depression (VMA and 5-HIAA), monitoring the effectiveness of therapy with antidepressants (VMA and 5-HIAA) and antipsychotics;
• diagnosis of malignant tumors of the gastrointestinal tract, especially with metastases of malignant carcinoid to the liver (serotonin and 5-HIAA are markers of malignancy);
• in gastroenterology - studies of metabolic disorders in dumping syndrome, biliary and intestinal dyskinesia, irritable bowel syndrome. (5-HIAA).

Preparation
Blood
It is recommended to donate blood in the morning, between 8 am and 12 pm. Blood is drawn on an empty stomach or after 6–8 hours of fasting. It is allowed to drink water without gas and sugar. On the eve of the examination, food overload should be avoided.

Before performing the analysis you must:

• do not eat bananas, avocados, cheese, tea, coffee, cocoa, beer two days before collecting biomaterial;
• do not take a number of medications two weeks before the examination (need to be discussed with a specialist);
• do not take diuretics two days before collecting biomaterial (must be discussed with a specialist);
• Avoid physical activity and stressful situations when collecting daily urine.

Daily urine

• In the morning, empty your bladder (this portion of urine is poured into the toilet). Record the time of urination, for example: “8:00”;
• for the next 24 hours, collect all excreted urine in a dry, clean container with a capacity of 2–3 liters;
• After urine collection is completed, the contents of the container must be accurately measured. The container must indicate the daily volume of urine (diuresis) in milliliters. For example: “Diuresis: 1250 ml”;
• Be sure to mix the urine thoroughly and immediately pour 30–50 ml into a sterile container with a lid. There is no need to bring all the urine collected during the day;
• During the entire collection period and until shipment, the biomaterial should be stored in a refrigerator at 2–8°C. The material must be delivered to the medical office on the day the collection ends.

To exclude false-positive results, it is advisable 48 hours before urine collection:

• exclude from the diet bananas, pineapples, tomatoes, eggs, chocolate, cheese, as well as food products containing vanillin (confectionery);
• it is necessary to limit as much as possible the intake of products containing caffeine and other stimulants (tea, coffee, cocoa, Coca-Cola);
• if possible, after consultation with the referring physician, avoid taking medications 1–2 days before the study, except those used for health reasons (see Interpretation: medications).

Interpretation of results
Units of measurement and conversion factors:

VMA – mg/day. Alternative units are µmol/day. Conversion of units: mg/day x 5.05 => µmol/day.

HVA – mcg/day. Alternative units are µmol/day. Conversion of units: m/day x 4.59 => µmol/day.

5-HIAA – mcg/day. Alternative units are µmol/day. Conversion of units: mg/day x 5.23 => µmol/day.

Increasing values
VMA - vanillyl mandelic acid:

• pheochromocytoma, neuroblastoma, ganglioneuroma;
• carcinoid (in some cases);
• medications: ajmaline, epinephrine, guanethidine (initial doses), histamine, insulin (after high dose or insulin shock), levodopa (slight increase), lithium, nitroglycerin, rauwolfia alkaloids (eg, reserpine, initial doses).

5-HIAA - 5-hydroxyindoleacetic acid:

• malignant intestinal carcinoid;
• ovarian carcinoid tumors, celiac sprue;
• tropical sprue;
• Whipple's disease;
• oat cell bronchial cancer;
• bronchial adenoma of carcinoid type;
• taking atenolol, fluorouracil, melphalan, pindolol, rauwolfia preparations (eg reserpine - weak effect), foods high in hydroxyindole (avocados, bananas, tomatoes, plums, walnuts, pineapples, eggplants).

HVA - homovanillic acid:

• malignant pheochromocytoma and neuroblastoma, ganglioblastoma;
• medications: disulfiram, L-dopa (if parkinsonism is treatable), pyridoxine (in complex treatment with L-dopa), reserpine (maximum on the second day after administration).

Lowering values
VMA:

• violation of preanalytics (alkaline urine);
• medications: chlorpromazine, clonidine (depending on dose), debrisoquin, disulfiram, guanethidine, hydrazine derivatives, imipramine, MAO inhibitors, morphine, radiocontrast agents (effect on excretion), reserpine.

5-HIAA:

• depression;
• small bowel resection;
• mastocytosis;
• phenylketonuria;
• Hartnup's disease (hereditary disorder of tryptophan metabolism);
• medications: corticotropin, ethanol, imipramine, isoniazid, levodopa, MAO inhibitors, methyldopa;
• HVA - drug interference (moclobimide).

It is considered one of the most important “mediators of wakefulness”. Noradrenergic projections participate in the ascending reticular activating system.

Norepinephrine synthesis

The precursor of norepinephrine is dopamine (it is synthesized from tyrosine, which, in turn, is a derivative of phenylalanine), which, with the help of the enzyme dopamine beta-hydroxylase, is hydroxylated (adds an OH group) to norepinephrine in the vesicles of synaptic terminals. At the same time, norepinephrine inhibits the enzyme that converts tyrosine into a precursor of dopamine, due to which self-regulation of its synthesis is carried out.

Norepinephrine receptors

There are alpha-1, alpha-2 and beta receptors for norepinephrine. Each group is divided into subgroups that differ in their affinity for different agonists, antagonists and, in part, functions. Alpha-1 and beta receptors can only be postsynaptic and stimulate adenylate cyclase, alpha-2 can be both post- and pre-synaptic and inhibit adenylate cyclase. Beta receptors stimulate lipolysis.

Degradation of norepinephrine

Norepinephrine has several degradation pathways, mediated by two enzymes: monoamine oxidase-A (MAO-A) and catechol-O-methyl-transferase (COMT). Ultimately, norepinephrine is converted to either 4-hydroxy-3-methoxyphenylglycol or vanillylmandelic acid.

Noradrenergic system

Norepinephrine is a neurotransmitter of the locus coeruleus (lat. locus coeruleus) of the brain stem and the endings of the sympathetic nervous system. The number of noradrenergic neurons in the central nervous system is small (several thousand), but they have a very wide field of innervation in the brain.

Norepinephrine as a hormone

The action of norepinephrine is associated with a predominant effect on α-adrenergic receptors. Norepinephrine differs from adrenaline in having a much stronger vasoconstrictor and pressor effect, a much smaller stimulating effect on heart contractions, a weak effect on the smooth muscles of the bronchi and intestines, and a weak effect on metabolism (the absence of a pronounced hyperglycemic, lipolytic and general catabolic effect). Norepinephrine increases the need for oxygen in the myocardium and other tissues to a lesser extent than adrenaline.

Norepinephrine takes part in the regulation of blood pressure and peripheral vascular resistance. For example, when moving from a lying position to a standing or sitting position, the level of norepinephrine in the blood plasma normally increases several times within a minute.

Norepinephrine is involved in the implementation of “fight or flight” reactions, but to a lesser extent than adrenaline. The level of norepinephrine in the blood increases during stress, shock, injury, blood loss, burns, anxiety, fear, and nervous tension.

The cardiotropic effect of norepinephrine is associated with its stimulating effect on β-adrenergic receptors of the heart, however, the β-adrenergic stimulating effect is masked by reflex bradycardia and increased vagal tone caused by increased blood pressure.

Norepinephrine causes an increase in cardiac output. Due to increased blood pressure, perfusion pressure in the coronary and cerebral arteries increases. At the same time, peripheral vascular resistance and central venous pressure increase significantly.

Dopamine (dopamine , D.A.) is a neurotransmitter produced in the brains of humans and animals. It is also a hormone produced by the adrenal medulla and other tissues (for example, kidneys), but this hormone almost does not penetrate into the subcortex of the brain from the blood. According to its chemical structure, dopamine is classified as a catecholamine. Dopamine is the biochemical precursor to norepinephrine (and adrenaline).

Neurotransmitter

Dopamine is one of the chemical factors of intrinsic reinforcement (ERC) and serves as an important part of the “reward system” of the brain, as it causes a feeling of pleasure (or satisfaction), which affects the processes of motivation and learning. Dopamine is naturally produced in large quantities during subjectively positive experiences - for example, sex, eating delicious food, pleasant bodily sensations, and drugs. Neurobiological experiments have shown that even memories of reward can increase dopamine levels, so this neurotransmitter is used by the brain for evaluation and motivation, reinforcing actions important for survival and procreation.

Dopamine plays an important role in ensuring cognitive activity. Activation of dopaminergic transmission is necessary during the processes of switching a person’s attention from one stage of cognitive activity to another. Thus, insufficiency of dopaminergic transmission leads to increased inertia of the patient, which is clinically manifested by slowness of cognitive processes (bradyphrenia) and perseverations. These disorders are the most typical cognitive symptoms of diseases with dopaminergic deficiency - for example, Parkinson's disease.

Like most neurotransmitters, dopamine has synthetic analogues, as well as stimulators of its release in the brain. In particular, many drugs increase the production and release of dopamine in the brain by 5-10 times, allowing people who use them to experience feelings of pleasure in an artificial way. Thus, amphetamine directly stimulates the release of dopamine, affecting its transport mechanism. Other drugs, such as cocaine and some other psychostimulants, block the natural mechanisms of dopamine reuptake, increasing its concentration in the synaptic space. Morphine and nicotine mimic the action of natural neurotransmitters, while alcohol blocks the action of dopamine antagonists. If the patient continues to overstimulate his reward system, the brain gradually adapts to the artificially increased dopamine levels, producing less of the hormone and reducing the number of receptors in the reward system, one of the factors that encourages the addict to increase the dose to get the same effect. Further development of chemical tolerance can gradually lead to metabolic disturbances in the brain, and in the long term, potentially cause serious damage to brain health.

Biosynthesis

The precursor to dopamine is L-tyrosine (synthesized from phenylalanine), which is hydroxylated by the enzyme tyrosine hydroxylase to form L-DOPA, which in turn is decarboxylated by the enzyme L-DOPA decarboxylase and converted to dopamine. This process occurs in the cytoplasm of the neuron.

Receptors

Postsynaptic dopamine receptors belong to the GPCR family. There are at least five different dopamine receptor subtypes - D 1-5. The D 1 and D 5 receptors have quite significant homology and are associated with the GS protein, which stimulates adenylate cyclase, as a result of which they are usually considered together as D 1 -like receptors. The remaining receptors of the subfamily are similar to D2 and are associated with the Gi protein, which inhibits adenylate cyclase, as a result of which they are combined under the general name D-2-like receptors. Thus, dopamine receptors play the role of modulators of long-term potentiation.

D 2 and D 4 receptors take part in “internal reinforcement”.

In high concentrations, dopamine also stimulates α- and β-adrenergic receptors. The effect on adrenergic receptors is associated not so much with direct stimulation of adrenergic receptors, but with the ability of dopamine to release norepinephrine from granular presynaptic depots, that is, to have an indirect adrenomimetic effect.

"Cycle" of dopamine[

Basic elements of a synapse

Dopamine synthesized by a neuron accumulates in dopamine vesicles (the so-called “synaptic vesicle”). This process is proton-coupled transport. H+ ions are pumped into the vesicle using a proton-dependent ATPase. When protons exit along the gradient, dopamine molecules enter the vesicle.

Next, dopamine is released into the synaptic cleft. Part of it is involved in the transmission of nerve impulses, acting on cellular D-receptors of the postsynaptic membrane, and part is returned to the presynaptic neuron using reuptake. Autoregulation of dopamine release is provided by D 2 and D 3 receptors on the membrane of the presynaptic neuron. Reuptake is carried out by the dopamine transporter. The mediator that returns to the cell is cleaved by monoamine oxidase (MAO) and, further, aldehyde dehydrogenase and catechol-O-methyl transferase to homovanillic acid.

Participation in the reward system

A laboratory rat in a special box presses a lever. Stimulators are attached to the animal's head.

In a seminal 1954 study, Canadian scientists James Olds and his colleague Peter Milner found that if electrodes were implanted in specific areas of the brain, especially the midforebrain ganglion, rats could be trained to press a lever in a cage that triggered low-voltage electrical stimulation. Once the rats learned to stimulate this area, they pressed the lever up to a thousand times per hour. This gave reason to assume that the pleasure center was being stimulated. One of the main pathways for the transmission of nerve impulses in this part of the brain is dopamine, so researchers have put forward the theory that the main chemical associated with pleasure is dopamine. This assumption was later confirmed by radionuclide tomographic scanners and the discovery of antipsychotics (medicines that suppress the productive symptoms of schizophrenia).

However, in 1997, dopamine was shown to play a more subtle role. In Schultz's experiment, a conditioned reflex was created in a monkey according to the classical Pavlovian scheme: after a light signal, juice was injected into the monkey's mouth. It was found that:

1. When the juice was injected unexpectedly (without preceding it with a signal), the activity of dopamine neurons increased.

2. During the learning stage, the activity of dopamine neurons continued to increase in response to the injection of juice.

3. When the conditioned reflex was formed, the activity of dopamine neurons increased after the signal was given (before the injection of juice). The injection of juice itself no longer affected the activity of these neurons (which contradicts the hypothesis that dopamine is simply associated with pleasure).

4. If juice was not injected at the moment when juice was expected, the activity of dopamine neurons decreased.

This suggested that dopamine is involved in the formation and consolidation of conditioned reflexes during positive reinforcement and in extinguishing them if the reinforcement stops. In other words, if our expectation of reward is met, the brain tells us this by releasing dopamine. If the reward does not follow, a decrease in dopamine levels signals that the model has diverged from reality. Further work showed that the activity of dopamine neurons is well described by the well-known model of automata learning: actions that quickly lead to receiving a reward are assigned greater value. Thus, learning occurs by trial and error [.

Dopaminergic system[

Of all the neurons in the central nervous system, only about seven thousand produce dopamine. There are several known dopamine nuclei located in the brain. This is the arcuate nucleus (lat. nucleus arcuatus), giving its processes to the median eminence of the hypothalamus. Dopamine neurons of the substantia nigra send axons to the striatum (caudate and lenticular nuclei). Neurons located in the ventral tegmental area give projections to the limbic structures and cortex.

Major dopamine pathways.

The main dopamine pathways are:

mesocortical pathway (motivational processes and emotional reactions)

Mesolimbic pathway (producing feelings of pleasure, reward and desire)

Nigrostriatal pathway (motor activity, extrapyramidal system)

Neuron cell bodies nigrostriatal, mesocortical And mesolimbic tracts form a complex of neurons of the substantia nigra and the ventral tegmental field. The axons of these neurons first run as part of one large tract (the medial forebrain bundle), and then diverge into various brain structures. Some authors combine the mesocortical and mesolimbic subsystems into a single system, but it is more reasonable to distinguish the mesocortical and mesolimbic subsystems according to projections to the frontal cortex and limbic structures of the brain.

In the extrapyramidal system, dopamine plays the role of a stimulating neurotransmitter, helping to increase motor activity, reduce motor retardation and stiffness, and reduce muscle hypertonicity. The physiological antagonists of dopamine in the extrapyramidal system are acetylcholine and GABA.

Other subsystems]

Also distinguished tuberoinfundibular tract(limbic system - hypothalamus - pituitary gland), incertohypothalamic, diencephalospinal And retinal(sometimes, in addition to this, periventricular And olfactory systems). This differentiation is not absolute, since the projections of dopaminergic neurons of different tracts “overlap”; In addition, a diffuse distribution of dopaminergic elements (individual cells with processes) is noted in the brain.

In the hypothalamus and pituitary gland, dopamine plays the role of a natural inhibitory neurotransmitter, inhibiting the secretion of a number of hormones. In this case, the inhibitory effect on the secretion of different hormones is realized at different concentrations of dopamine, which ensures high specificity of regulation. The secretion of prolactin is most sensitive to the inhibitory effect of dopaminergic signals, to a lesser extent - the secretion of somatoliberin and somatotropin, to an even lesser extent - the secretion of corticotropin and corticotropin, and to a very small extent - the secretion of thyrotropin and thyrotropin. The secretion of gonadotropins and GnRH is not inhibited by dopaminergic signals.

Due to the sensitivity of some hormonal subsystems to dopamine levels, dopaminomimetic drugs that enhance its synthesis can be used as therapy for hormonal diseases. For example, dopaminomimetics are prescribed for hyperprolactinemia and Parkinson's disease.

Phenylethylamines or catecholamines - what are they? These are active substances that act as mediators in intercellular chemical interactions in the human body. These include: norepinephrine (norepinephrine), which are hormonal substances, as well as dopamine, which is a neurotransmitter.

general information

Catecholamines - what are they? These are several hormones that are produced in the adrenal gland, its medulla and enter the bloodstream as a response to an emotional or physical stressful situation. Further, these active substances take part in the transmission of nerve impulses to the brain and provoke:

• release of energy sources, which are fatty acids and glucose;
• dilation of pupils and bronchioles.

Norepinephrine directly increases blood pressure by constricting blood vessels. Adrenaline acts as a metabolic stimulant and increases heart rate. After the hormonal substances have completed their work, they disintegrate and are excreted from the body along with urine. Thus, the functions of catecholamines are that they provoke the endocrine glands to work actively, and also help stimulate the pituitary gland and hypothalamus. Normally, catecholamines and their metabolites are contained in small quantities. However, under stress, their concentration increases for some time. In some pathological conditions (chromaffin tumors, neuroendocrine tumors), a huge amount of these active substances is formed. Tests can detect them in blood and urine. In this case, the following symptoms appear:

• increased blood pressure for a short or long period;
• very severe headaches;
• trembling in the body;
• increased sweating;
• prolonged anxiety;
• nausea;
• slight tingling in the limbs.

Surgery aimed at removing it is considered an effective method of treating tumors. As a result, catecholamine levels decrease and symptoms decrease or disappear.

Mechanism of action

The effect is to activate membrane receptors located in the cellular tissue of target organs. Further, protein molecules, changing, trigger intracellular reactions, due to which a physiological response is formed. Hormonal substances produced by the adrenal glands and thyroid gland increase the sensitivity of receptors to norepinephrine and adrenaline.

These hormonal substances affect the following types of brain activity:

• aggressiveness;
• mood;
• emotional stability;
• reproduction and assimilation of information;
• quick thinking;
• participate in shaping behavior.

In addition, catecholamines provide energy to the body. A high concentration of this complex of hormones in children leads to their mobility and cheerfulness. As the child grows older, the production of catecholamines decreases, and the child becomes more restrained, the intensity of mental activity decreases somewhat, and possibly a deterioration in mood. By stimulating the hypothalamus and pituitary gland, catecholamines help increase the activity of the endocrine glands. Intense physical or mental stress, which increases the heart rate and body temperature, leads to an increase in catecholamines in the bloodstream. The complex of these active substances acts rapidly.

Types of catecholamines

Catecholamines - what are they? These are biologically active substances that, due to their instant response, allow the individual’s body to work ahead of the curve.

1. Norepinephrine. This substance has another name - the hormone of aggression or rage, since when it enters the bloodstream, it provokes irritability and an increase in muscle mass. The amount of this substance is directly related to large physical overloads, stressful situations or allergic reactions. Excess norepinephrine, having a constricting effect on blood vessels, has a direct effect on the speed of circulation and blood volume. The person's face takes on a red tint.
2. Adrenalin. The second name is the fear hormone. Its concentration increases with excessive worries, stress, both physical and mental, as well as with severe fear. This hormonal substance is formed from norepinephrine and dopamine. Adrenaline, by constricting blood vessels, provokes an increase in pressure and affects the rapid breakdown of carbohydrates, oxygen and fats. The individual’s face takes on a pale appearance, and endurance increases during severe excitement or fear.
3. Dopamine. This active substance, which is involved in the production of norepinephrine and adrenaline, is called the happiness hormone. It has a vasoconstrictor effect on the body, provokes an increase in the concentration of glucose in the blood, suppressing its utilization. Inhibits the production of prolactin and affects the synthesis of growth hormone. Dopamine affects sex drive, sleep, thought processes, joy, and pleasure from eating. An increase in the excretion of dopamine from the body along with urine is detected in the presence of tumors of a hormonal nature. In brain tissue, the level of this substance increases with a lack of pyridoxine hydrochloride.

Biological action of catecholamines

Adrenaline significantly affects cardiac activity: it increases the conductivity, excitability and contractility of the myocardial muscle. Under the influence of this substance, blood pressure increases, and also increases:

• strength and heart rate;
• minute and systolic blood volume.

Excessive concentration of adrenaline can provoke:

• arrhythmia;
• in rare cases, ventricular fibrillation;
• disruption of oxidation processes in the heart muscle;
• changes in metabolic processes in the myocardium, up to dystrophic changes.

Unlike adrenaline, norepinephrine does not have a significant effect on cardiac activity and causes a decrease in heart rate.

Both hormonal substances:

• They have a vasoconstrictor effect on the skin, lungs and spleen. In adrenaline this process is more pronounced.
• They dilate the coronary arteries of the stomach and heart, while the effect of norepinephrine on the coronary arteries is stronger.
• They play a role in the metabolic processes of the body. Adrenaline has the predominant effect.
• Helps reduce muscle tone in the gallbladder, uterus, bronchi, and intestines. Norepinephrine is less active in this case.
• They cause a decrease in eosinophils and an increase in neutrophils in the blood.

In what cases is a urine test prescribed?

Analysis for catecholamines in urine makes it possible to identify disorders that, due to pathological processes, lead to disruption of the normal functioning of the body. Failures can be caused by various serious illnesses. This type of laboratory test is prescribed in the following cases:

1. To monitor therapy in the treatment of chromaffin tumors.
2. In case of neuroendocrine or identified neoplasm of the adrenal glands, or genetic predisposition to tumor formation.
3. For hypertension that cannot be treated.
4. Presence of hypertension with constant headache, rapid heart rate and increased sweating.
5. Suspicion of a chromaffin neoplasm.

Preparing for a urine test

Determination of catecholamines helps confirm the presence of pathological processes in the human body, for example, high blood pressure and cancer, as well as verify the effectiveness of treatment for pheochromocytoma and neuroblastoma. For accurate analysis results, you should undergo preparation, which consists of the following:

• Two weeks before the procedure, do not take medications that affect the increased release of norepinephrine from the endings of adrenergic nerves, in agreement with the treating doctor.
• Do not take medications that have a diuretic effect for two days. Exclude tea, coffee, alcohol-containing drinks, cocoa, beer, as well as cheese, avocados and other exotic vegetables and fruits, all legumes, nuts, chocolate, and all products that contain vanillin.
• During the day and during the period of daily urine collection, avoid any overexertion and avoid smoking.

Immediately before collecting urine for catecholamine analysis, perform genital hygiene. Biological material is collected three times a day. The first morning portion is not taken. Three hours after this, urine is collected, the second time - after six and then, after 12 hours. Before being sent to the laboratory, the collected biomaterial is stored in a sterile container placed in a special box or refrigerator at a certain temperature. The container for collecting urine indicates the time of the first and last emptying of the bladder, the patient’s personal data, and date of birth.

for catecholamines

In the laboratory, the biomaterial is examined for several indicators, which depend on the age and gender of the individual. The unit of measurement for hormones is mcg/day; each type has its own standards:

• Adrenalin. Acceptable values ​​for citizens over 15 years of age are 0-20 units.
• Norepinephrine. The norm for the age category from 10 years is 15-80.
• Dopamine. The indicator corresponds to normal values ​​of 65-400 at the age of 4 years.

The results of studies of catecholamines in urine are influenced by various factors. And since pathology in the form of a chromaffin tumor is quite rare, the indicators are often false positive. In order to reliably diagnose the disease, additional types of examinations are prescribed. If elevated levels of catecholamines are detected in patients with an already established diagnosis, this fact indicates a relapse of the disease and the ineffectiveness of the therapy. It should be remembered that taking certain groups of medications, stress, drinking alcohol, coffee and tea affects the final result of the research. Pathologies in which an increased concentration of catecholamines is detected:

• liver diseases;
• hyperthyroidism;
• myocardial infarction;
• angina pectoris;
• bronchial asthma;
• peptic ulcer of the duodenum or stomach;
• head injury;
• long-term depression;
• arterial hypertension.

Low levels of hormonal substances in urine indicate diseases:

• kidney;
• leukemia;
• various psychoses;
• underdevelopment of the adrenal glands.

Preparing for a blood test for catecholamines

14 days before taking samples, it is necessary to exclude medications containing sympathomimetics (in consultation with the treating doctor). For two days, exclude from the diet: beer, coffee, tea, cheese, bananas. Quit smoking in a day. Refrain from eating for 12 hours.

Blood is taken through a catheter, which is installed one day before taking biomaterial samples due to the fact that puncture of the vein also increases the concentration of catecholamines in the blood.

Panel “Blood catecholamines” and serotonin + urine test for GVK, VVK, 5-OIUC

Using such a panel, the content of catecholamines is determined: serotonin, dopamine, norepinephrine, adrenaline and their metabolites. The indications for this study are as follows:

• determination of the causes of hypertensive crises and arterial hypertension;
• for the purpose of diagnosing neoplasms of nervous tissue and adrenal glands.

More information can be obtained when prescribing a daily urine analysis to determine the level of catecholamines due to the fact that their synthesis during this period is influenced by:

• pain;
• cold;
• stress;
• injuries;
• heat;
• physical stress;
• asphyxia;
• any types of loads;
• bleeding;
• use of drugs of a narcotic nature;
• lowering blood glucose levels.

With diagnosed arterial hypertension, the concentration of catecholamines in the blood approaches the highest level of normal values, and in some cases approximately doubles. In a stressful situation, adrenaline in the blood plasma increases tenfold. Due to the fact that catecholamines in the blood are neutralized quite quickly, it is appropriate to detect them in urine to diagnose pathological conditions. Practicing doctors prescribe tests for the concentration of norepinephrine and epinephrine mainly to diagnose hypertension and pheochromocytoma. In young children, in order to confirm neuroblastoma, it is important to determine the metabolites of norepinephrine and adrenaline, as well as dopamine.

In order to obtain reliable information about catecholamines, urine analysis also determines the presence of their breakdown products: HVA (homovanillic acid), VMA (vanillylmandelic acid), normetanephrine, metanephrine. The excretion of metabolic products normally exceeds the excretion of a complex of hormonal substances. The concentration of metanephrine and ICH in urine is greatly increased in pheophromocytoma, which is important for making a diagnosis.

It is a breakdown product of adrenaline and norepinephrine; it is detected in a daily analysis for catecholamines. Indications for the analysis are neuroblastomas, tumors and evaluation of the adrenal glands, hypertension and crises. The study of this metabolite allows us to draw a conclusion about the synthesis of adrenaline and norepinephrine, and also helps in the diagnosis of neoplasms and assessment of the adrenal medulla.

Serotonin

In oncological practice, to detect a special type of tumor with argentaffin, a blood indicator such as the catecholamine serotonin is important. It is considered one of and is a highly active biogenic amine. The substance has a vasoconstrictor effect, takes part in the regulation of temperature, respiration, pressure, kidney filtration, stimulates the smooth muscles of the intestine, blood vessels, and bronchioles. Serotonin can cause platelet aggregation. Its content in the body is detected using the metabolite 5-OHIAA (hydroxyindoleacetic acid) of urine. The serotonin content is increased in the following cases:

• carcinoid tumor of the abdominal cavity with metastases;
• hypertensive crises with a diagnosis of pheochromocytoma;
• neuroendocrine tumors of the prostate, ovaries, intestines, bronchi;
• pheochromocytomas;
• metastasis or incomplete removal of the tumor after surgery.

In the body, serotonin is converted into hydroxyindoleacetic acid and is excreted in the urine. The concentration of this substance in the blood is determined by the amount of metabolite excreted.

Catecholamines - what are they? These are useful substances for any individual, necessary for the body’s immediate response to an irritant: stress or fear. A blood test shows the presence of hormones immediately at the time of taking the biomaterial, and a urine test shows only the previous day.

Description

Determination method High performance liquid chromatography.

Material under study Blood plasma

Home visit available

The study is used in the diagnosis of pheochromocytomas, differential diagnosis of hypertensive conditions, dysfunction of the sympathadrenal system and pathological conditions associated with changes in serotonin levels.

Adrenalin. A representative of catecholamines, the main hormone of the adrenal medulla. It is formed in the adrenal glands as a result of enzymatic synthesis from norepinephrine and accumulates in chromaffin cells. Secreted in increased quantities in states of stress and blood loss. Provides an increase in blood pressure by constricting blood vessels in the skin, gastrointestinal tract and skeletal muscles, increases coronary blood flow, strengthens and increases heart rate, and increases blood glucose levels. The main source of adrenaline in the blood is the adrenal glands.

Norepinephrine. Catecholamine. Neurotransmitter and hormone. It is formed from dopamine in the postganglionic cells of the sympathetic nervous system, the adrenal medulla, and the central nervous system. It acts in many ways similar to adrenaline. Norepinephrine in the blood comes primarily from sympathetic nerve endings, about 7% from the adrenal medulla.

Dopamine. Catecholamine. Neurotransmitter of the central nervous system (damage to the dopaminergic system is associated with the pathogenesis of Parkisnon's disease), a precursor of norepinephrine and adrenaline during their synthesis, a mediator of non-nervous local (paracrine) regulation in a number of peripheral organs (including the mucous membrane of the gastrointestinal tract, kidneys). A minor part of blood dopamine comes from the nervous system, less than 2% is contributed by the adrenal glands. A significant part of the dopamine entering the circulation is formed in the gastrointestinal tract; a significant amount of free dopamine excreted in the urine (but not conjugates and metabolites) is formed in the kidneys.

The study of catecholamines in plasma and urine is used mainly in the diagnosis of pheochromocytomas, paragangliomas, neuroblastomas, and differential diagnosis of hypertensive conditions. The ratio of plasma catecholamine fractions is important for determining the location and nature of catecholamine-secreting tumors.

Scheme of catecholamine biosynthesis in the adrenal medulla: tyrosine - DOPA - dopamine - norepinephrine - adrenaline. In sympathetic nerve endings, synthesis proceeds to the stage of norepinephrine. Cells similar to the chromaffin cells of the adrenal medulla are found in other tissues, and islands of such tissue function similarly to the adrenal medulla and are subject to similar pathological changes. With pheochromocytoma, the secretion of catecholamines increases tens and sometimes hundreds of times, but the level between attacks in normotensive patients may be lower or normal. In hypertension, the level of catecholamines in the blood is at the upper limit of normal or increased by 1.5-2 times. Plasma norepinephrine levels in pheochromocytoma are higher than adrenaline levels. Pheochromocytomas of adrenal origin are characterized by an increase in the level of both adrenaline and norepinephrine, while extra-adrenal tumors usually increase only the content of norepinephrine; An increase in dopamine levels is characteristic of neuroblastoma. An increase in dopamine is observed more often in malignant tumors. Studying the level of catecholamines over time allows not only to diagnose pheochromocytoma, but also to monitor the effectiveness of the therapy. Radical removal of the tumor is always accompanied by rapid normalization of parameters, and recurrence of the process leads to a repeated increase in the concentration of catecholamines in the blood. The study of plasma catecholamines is useful in the diagnosis of orthostatic hypotension - the absence of an increase in norepinephrine when moving from the lying to standing position confirms dysfunction of the sympathetic nervous system.

The duration of action of catecholamines circulating in the blood is relatively short; their half-life from the circulation is measured in minutes. Excretion mechanisms: reuptake by sympathetic nerve endings, conversion by enzymes into inactive forms, metabolism in the liver, excretion by the kidneys in the urine. Ideally, blood collection for this study should be performed at the time of significant clinical manifestations (hypertensive crisis, etc.), which in practice is not always feasible.

When studying blood catecholamines, both false-negative and false-positive test results (associated with physiological or chemical interference) cannot be excluded. Therefore, studies of the excretion of fractionated catecholamines and/or their metabolites in urine (24-hour or post-crisis) are the preferred screening tests for pheochromocytoma (see tests No. 151, 152, 918, 952). But to assess the location of the tumor (using selective selection of the vein) or when conducting pharmacological tests, as well as in the case of questionable results of urine analysis, but strong clinical suspicions, plasma catecholamine studies are used. In case of attacks of paroxysmal hypertension significantly separated in time, the study of plasma catecholamines is used during the period of pronounced clinical symptoms. It should also be borne in mind that the determination of catecholamines in urine may not be sufficiently informative if the patient has impaired renal function.

Literature

1. Clinical laboratory diagnostics. National leadership. Volume. 1. M. GEOTAR-Media, 2012, 928 p.
2. Dufour D. Clinical use of laboratory data: a practical guide. - Williams & Wilkins. - 1998 - 606 p.
3. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 4 ed. Ed. Burtis C.A., Ashwood E.R., Bruns D.E. Elsevier. New Delhi.2006. 2412 p.
4. CanditoM.etal.Plasma catecholamine levels in children. J. Chromatogr. 1993, Vol 617(2), p.304-307.

Preparation

It is preferable to take blood in the morning on an empty stomach, after 8-14 hours of overnight fasting (you can drink water), or 4 hours after a light meal during the day.

On the eve of the study, it is necessary to exclude increased psycho-emotional and physical stress (sports training), alcohol intake, and smoking an hour before the study.

For a few days, eliminate bananas, pineapples, cheese, strong tea and coffee, and products containing vanillin from your diet.

You should discuss with your doctor the advisability of conducting the study while you are currently taking medications.

A few days before the study (preferably approximately 5 half-lives of the drug), teracycline antibiotics, quinidine, reserpine, tranquilizers, adrenergic blockers, and MAO inhibitors are stopped.

The patient should be at rest for 20-30 minutes before taking blood.

Indications for use

1. Diagnosis and monitoring of catecholamine-secreting tumors - pheochromocytomas, paragangliomas, neuroblastomas, assessment of endocrine causes of increased blood pressure (during the period of pronounced clinical manifestations in patients with individual episodes of paroxysmal hypertension).
2. In a complex of in-depth studies for conditions associated with dysfunction of the sympathetic nervous system (including congestive heart failure, orthostatic disorders, panic attacks; metabolic disorders in obesity, diabetes; acute asthma, migraine, mental depression, etc.).

Interpretation of results

Interpretation of research results contains information for the attending physician and is not a diagnosis. The information in this section should not be used for self-diagnosis or self-treatment. The doctor makes an accurate diagnosis using both the results of this examination and the necessary information from other sources: medical history, results of other examinations, etc.

Units of measurement in the Independent Laboratory INVITRO:

Adrenaline - pg/ml. (Alternative units are pmol/l. Unit conversion: pg/ml x 5.46 => pmol/l).

Norepinephrine - pg/ml. (Alternative units are pmol/l. Unit conversion: pg/ml x 5.91 => pmol/l).

Dopamine – pg/ml. (Alternative units are pmol/l. Unit conversion: pg/ml x 6.53 => pmol/l).

Reference values ​​for adults* (sitting, 20 minutes rest):

Adrenaline –<110 пг/мл;

Norepinephrine 70-750 pg/ml

Excitement, intense physical activity, transition to a standing position;

hypertensive crisis, stress;

hypoglycemia;

acute myocardial infarction;

traumatic brain injury;

ketoacidosis in patients with diabetes mellitus;

congestive heart failure;

chronic alcoholism, especially delirium tremens;

manic phase of manic-depressive syndrome;

use of drugs: ether, ethanol, caffeine, ajmaline, diazoxide, isoproterenol, MAO inhibitors, nitroglycerin, theophylline, phentolamine, propranolol, L-dopa, methyldopa.

Aminophenols include compounds in which the NH 2 and OH functional groups are attached to the benzene ring.

Two derivatives of n-aminophenol are used in medicine as analgesics and antipyretics. This is paracetamol and, to a lesser extent, phenacetin

Catecholamines - dopamine, norepinephrine, adrenaline - biogenic amines, metabolic products of the amino acid phenylalanine.

Catecholamines act as hormones and neurotransmitters. Adrenaline is a hormone of the adrenal medulla, norepinephrine and dopamine are its precursors. An increase in catecholamine concentrations is a typical response to stress. Their role is to mobilize the body to carry out active brain and muscle activity.

Dopamine– hormone, neurotransmitter, improves oxygen delivery, increases the strength of heart contractions, kidney function, affects motor activity.

The hormone dopamine is produced by the adrenal medulla, and the neurotransmitter dopamine is produced by an area of ​​the midbrain called the corpus nigra.

Dopamine neurotransmitter. There are four known “dopamine pathways” - brain pathways in which dopamine plays the role of carrier of nerve impulses. One of them, the mesolimbic pathway, is considered responsible for producing feelings of pleasure. Dopamine is also believed to be involved in human decision making. At least among people with dopamine synthesis/transport disorders, many have difficulty making decisions. This is due to the fact that dopamine is responsible for the “feeling of reward,” which often allows you to make a decision by thinking about this or that action on a subconscious level.

Adrenalin or methylaminoethanolpyrocatechol, is produced in the adrenal glands and is a hormone that implements “fight or flight” reactions. Its secretion increases sharply during stressful conditions, borderline situations, feelings of danger, anxiety, fear, injuries, burns and shock.

Adrenalin:

Strengthens and increases heart rate

Causes vasoconstriction of muscles, abdominal cavity, mucous membranes

Relaxes the intestinal muscles and dilates the pupils.

The main task of adrenaline is to adapt the body to a stressful situation. Adrenaline improves the functional ability of skeletal muscles. With prolonged exposure to adrenaline, an increase in the size of the myocardium and skeletal muscles is noted. However, prolonged exposure to high concentrations of adrenaline leads to increased protein metabolism, decreased muscle mass and strength, weight loss and exhaustion. This explains emaciation and exhaustion during distress (stress that exceeds the body's adaptive capabilities).

Adrenaline increases blood pressure, and therefore stress can contribute to a persistent increase in blood pressure and cardiovascular disease.

Adrenaline is often used as a hemostatic agent. It is obtained from the adrenal glands, as well as synthetically from pyrocatechol. Interestingly, only levorotatory (natural) adrenaline has biological activity, while dextrorotatory adrenaline is biologically inactive.

Norepinephrine- hormone and neurotransmitter. Norepinephrine also increases with stress, shock, trauma, anxiety, fear, and nervous tension. Unlike adrenaline, the main effect of norepinephrine is solely to constrict blood vessels and increase blood pressure. The vasoconstrictor effect of norepinephrine is greater, although its duration of action is shorter.

Both adrenaline and norepinephrine can cause tremors - that is, trembling of the limbs and chin. This reaction is especially clear in children aged 2-5 years, when a stressful situation occurs.

Immediately after identifying a situation as stressful, the hypothalamus releases corticotropin (adrenocorticotropic hormone) into the blood, which, upon reaching the adrenal glands, stimulates the synthesis of norepinephrine and adrenaline.

The “invigorating” effect of nicotine is ensured by the release of adrenaline and norepinephrine into the blood. On average, it takes about 7 seconds after inhaling tobacco smoke for nicotine to reach the brain. In this case, there is a short-term acceleration of the heartbeat, an increase in blood pressure, increased breathing and an improvement in blood supply to the brain. The accompanying release of dopamine contributes to the consolidation of nicotine addiction.

Monocarboxylic acids: chemical properties involving the carboxyl group: (formation of salts, esters, amides, anhydrides). Functional derivatives of carboxylic acids - thioesters - (AcetylCoA, AcylCoA).

Carboxylic acids containing one carboxyl group are called monobasic, two are called dibasic, etc. When carboxylic acids interact with alkalis, carbonates and bicarbonates, salts are formed:

The most important reactions of monocarboxylic acids are shown in Scheme 1.

Scheme 1. Some nucleophilic substitution reactions in carboxylic acids

The esterification reaction is catalyzed by strong acids.

Thioesters- sulfur analogues of esters - find very limited use in classical organic chemistry, but play an important role in the body. It is known that in order to exhibit catalytic activity, most enzymes of a protein nature require the participation of coenzymes, which are low-molecular organic compounds of a non-protein nature that are diverse in structure. One of the groups of coenzymes consists of acyl coenzymes, which act as acyl group carriers. Of these, acetyl coenzyme A is the most common. Despite the complexity of the structure of the acetyl coenzyme A molecule, from the standpoint of a chemical approach, it can be determined that this coenzyme functions as a thioester. The thiol involved in its formation is coenzyme A (abbreviated as CoASH), the molecule of which is built from the residues of three components - 2-aminoethanethiol, pantothenic acid and adenosine diphosphate (additionally phosphorylated at position 3 in the ribose fragment). Adenosine diphosphate (ADP) is considered further as a representative of another important group of coenzymes - nucleoside polyphosphates. Pantothenic acid forms, on the one hand, an amide bond with 2-aminoethanethiol, and on the other, an ester bond with the ADP residue.

In terms of acylating ability, all acyl coenzymes A, including acetyl coenzyme A, being thioesters, occupy the “golden mean” between highly reactive anhydrides and low-active carboxylic acids and esters. Their rather high activity is due, in particular, to the increased stability of the leaving group - the CoA-S- anion - compared to the hydroxide and alkoxide ions of acids and esters, respectively.

Acetyl coenzyme A in vivo is a carrier of acetyl groups to nucleophilic substrates.

In this way, for example, acetylation of hydroxyl-containing compounds is carried out.

With the use of acetyl coenzyme A, choline is converted into acetylcholine, which is an intermediary in the transmission of nervous excitation in nerve tissues (neurotransmitter).

In addition, we can note the important participation in metabolic processes of coenzyme A itself, functioning as a thiol. In the body, any carboxylic acids are activated by conversion into reactive derivatives - thioesters.

AcylCoA formed by activation of fatty acids. Free fatty acid, regardless of the length of the hydrocarbon chain, is metabolically inert and cannot undergo any biochemical transformations, including oxidation, until it is activated. Activation of the fatty acid occurs on the outer surface of the mitochondrial membrane with the participation of ATP, coenzyme A (HS-KoA) and Mg 2+ ions. The reaction is catalyzed by the enzyme acyl-CoA synthetase:

As a result of the reaction, acyl-CoA, which is the active form of fatty acid.

Saturated dicarboxylic acids: oxalic, malonic, succinic, glutaric. Salts of oxalic acid are oxalates. The conversion of succinic acid to fumaric acid is an example of a biological dehydrogenation reaction.

This section will consider some representatives of dicarboxylic acids of the aliphatic and aromatic series (Table 1). All of them are crystalline substances.

Table 1. Names of some dicarboxylic acids and their derivatives

Systematic names of dicarboxylic acids are constructed according to the general rules of substitutive nomenclature. However, for most of them, trivial names are preferred. Their Latin names serve as the basis for the names of anions and acid derivatives, which often do not coincide with Russian trivial names (see Table 1).

Oxalic acid- the simplest dibasic acid. Some of its salts, such as calcium oxalate, are poorly soluble and often form kidney and bladder stones (oxalate stones).

succinic acid was found in noticeable quantities in amber, from which the acid itself and its derivatives succinates (from the Latin succinium - amber) got their name.

Glutaric acid (Pentanedioic acid) is a dibasic saturated carboxylic acid. It has fairly high solubility in water. Used in the production of polymers such as polyester and polyamides.

The keto derivative of glutaric acid, α-ketoglutaric acid (α-ketoglutarate), is an important biological compound. This keto acid is formed during the deamination of glutamate, and is one of the intermediate products of the Krebs cycle.

Oxalates- salts and esters of oxalic acid. The salts contain the dianion (oxalate) C 2 O 4 2− or (COO) 2 2−, formed by the double deprotonation of oxalic acid.

Most oxalate salts are slightly soluble in water, such as calcium oxalate, which is used to detect calcium. Potassium and ammonium oxalate are highly soluble.

The oxalate anion can act as a bidentate ligand, forming a five-membered MO 2 C 2 ring, as in potassium ferrioxalate - K 3 . Due to its good solubility, oxalic acid is used to remove rust.

Oxalates are widely distributed in nature, for example in sorrel. The roots and/or leaves of rhubarb and buckwheat contain oxalic acid. The accumulation of oxalic acid occurs due to incomplete oxidation of carbohydrates during the biosynthesis process.

The following edible plants contain oxalates in order of decreasing concentration: black pepper, parsley, poppy seeds, spinach, sugar beets, cocoa, chocolate, most nuts and berries, and beans.

The leaves of the tea bush contain a high relative amount of oxalates relative to other plants. Typically, its extracts contain low to medium concentrations of oxalates due to the low mass of leaves used.

The affinity of oxalate for divalent cations is reflected in the ability to form insoluble precipitates. So in the body, oxalate combines with cations such as Ca 2+, Fe 2+ and Mg 2+. As a result, crystals of the corresponding oxalates accumulate, which, due to their shape, irritate the intestines and kidneys. Because oxalates bind important elements such as calcium, eating foods high in oxalates for long periods of time can cause health problems.

A healthy person can safely eat foods with oxalates in moderation, but for people with kidney disease, gout, or rheumatoid arthritis, it is recommended to avoid foods with high amounts of oxalates. Calcium oxalate crystals, more commonly known as kidney stones, clog the kidney ducts. It is believed that 80% of kidney stones are formed from calcium oxalate.

Likewise, large intakes of calcium combined with foods containing oxalates lead to the deposition of calcium oxalate in the digestive tract, reducing oxalate intake by 97%.

Oxidation of succinic acid in vivo. The dehydrogenation (oxidation) of succinic acid into fumaric acid, catalyzed in the body by an enzyme, is carried out with the participation of the coenzyme FAD. The reaction proceeds stereospecifically with the formation of fumaric acid (in ionic form - fumarate).

Succinate dehydrogenase (EC 1.3.99.2) catalyzes the conversion of succinic acid to fumaric acid. The enzyme cofactor is FAD. The enzyme is tightly bound to the inner mitochondrial membrane.