Microsomal oxidation: a set of reactions

The role of microsomal oxidation in the life of the body is difficult to overestimate or not notice. Inactivation of xenobiotics (toxic substances), decay and formation of adrenal hormones, participation in the exchange of proteins and preservation of genetic information is only a small known number of problems that are solved due to microsomal oxidation. This is an autonomous process in the body, which is triggered after the hit of the trigger substance and ends with its ellimination.

Definition

Microsomal oxidation is a cascade of reactions that enter the first phase of xenobiotic conversion. The essence of the process is the hydroxylation of substances using oxygen atoms and the formation of water. This changes the structure of the original substance, and its properties can both be suppressed and strengthened.

Microsomal oxidation allows us to proceed to the conjugation reaction. This is the second phase of the transformation of xenobiotics, at the end of which molecules that are produced inside the organism will join the already existing functional group. Sometimes intermediate substances are formed that cause damage to the liver cells, necrosis and cancer tissue degeneration.

Oxidation-type oxidation

The reactions of microsomal oxidation take place outside the mitochondria, so they consume about ten percent of all the oxygen that enters the body. The main enzymes in this process are oxidases. In their structure there are atoms of metals with variable valence, such as iron, molybdenum, copper and others, and therefore they are able to receive electrons. In the cell, oxidases are located in special vesicles (peroxisomes) that are located on the outer membranes of mitochondria and in EPR (granular endoplasmic reticulum). Substrate, getting on peroxisomes, loses hydrogen molecules, which join the water molecule and form peroxide.

There are only five oxidases:

- monoaminooxygenase (MAO) - helps oxidize adrenaline and other biogenic amines formed in the adrenal glands;

- diaminooxygenase (DAO) - is involved in the oxidation of histamine (mediator of inflammation and allergy), polyamines and diamines;

- L-amino acid oxidase (i.e., levorotatory molecules);

- oxidase of D-amino acids (dextrorotatory molecules);

- xanthine oxidase - oxidizes adenine and guanine (nitrogenous bases entering the DNA molecule).

The significance of microsomal oxidation by the oxidase type is in the elimination of xenobiotics and the inactivation of biologically active substances. The formation of peroxide, which has bactericidal action and mechanical purification at the site of injury, is a side effect that occupies an important place among other effects.

Oxygenase oxidation

Oxygenase-type reactions in the cell also occur on the granular endoplasmic reticulum and in the outer envelopes of the mitochondria. This requires specific enzymes - oxygenases, which mobilize an oxygen molecule from the substrate and incorporate it into the oxidizable substance. If one oxygen atom is introduced, the enzyme is called monooxygenase or hydroxylase. In the case of the introduction of two atoms (that is, an entire molecule of oxygen), the enzyme is called diaksigenase.

Oxygenase oxidation reactions are part of a three-component multi-enzyme complex that participates in the transfer of electrons and protons from the substrate followed by activation of oxygen. The whole process occurs with the participation of cytochrome P450, which will be described in more detail.

Examples of reactions of the oxygenase type

As mentioned above, monooxygenases for oxidation use only one oxygen atom of the two available. The second they attach to two molecules of hydrogen and form water. One example of such a reaction is the formation of collagen. The donor of oxygen in this case is vitamin C. Proline hydroxylase takes from him an oxygen molecule and gives it to the proline, which, in turn, enters the procollagen molecule. This process gives strength and elasticity of the connective tissue. When the body lacks vitamin C, then gout develops. It is manifested by the weakness of connective tissue, bleeding, bruising, tooth loss, that is, the quality of collagen in the body becomes lower.

Another example is hydroxylase, which converts cholesterol molecules. This is one of the stages of the formation of steroid hormones, including sex.

Low-specific hydroxylases

These are the hydrolases necessary for the oxidation of foreign substances, such as xenobiotics. The meaning of the reactions is to make such substances more pliable for excretion, more soluble. This process is called detoxification, and it occurs for the most part in the liver.

Due to the inclusion of an entire oxygen molecule in xenobiotics, the cycle of reactions is ruptured and the decomposition of one complex substance into several simpler and more accessible ones for metabolic processes.

Active forms of oxygen

Oxygen is a potentially dangerous substance, since, in fact, oxidation is a process of combustion. In the form of a molecule of O ₂ or water, it is stable and chemically inert, because its electrical levels are filled, and new electrons can not join. But compounds in which oxygen does not have all the electrons have a vapor have a high reactivity. Therefore they are called active.

Such oxygen compounds:

1. In the monoxide reactions, a superoxide is formed, which is separated from the cytochrome P450.
2. Oxidase reactions produce the formation of a peroxide anion (hydrogen peroxide).
3. During the reoxygenation of tissues that underwent ischemia.

The strongest oxidant is the hydroxyl radical, it exists in a free state for only a millionth of a second, but during this time many oxidative reactions can pass. Its peculiarity is that the hydroxyl radical acts on substances only in the place in which it was formed, since it can not penetrate through the tissues.

Superoxidanion and hydrogen peroxide

These substances are active not only in the place of formation, but also at some distance from them, since they can penetrate through the cell membranes.

The hydroxyl group causes oxidation of amino acid residues: histidine, cysteine and tryptophan. This leads to inactivation of enzyme systems, as well as disruption of transport proteins. In addition, microsomal oxidation of amino acids leads to the destruction of the structure of nucleic nitrogen bases and, as a result, the genetic apparatus of the cell suffers. Oxidized and fatty acids, which are part of the bilipid layer of cell membranes. This affects their permeability, the operation of membrane electrolyte pumps and the location of receptors.

Inhibitors of microsomal oxidation are antioxidants. They are contained in food and are produced inside the body. The most famous antioxidant is vitamin E. These substances can inhibit microsomal oxidation. Biochemistry describes the interaction between them on the principle of feedback. That is, the more oxidases, the stronger they are suppressed, and vice versa. This helps maintain balance between systems and the constancy of the internal environment.

Electric transport chain

The microsomal oxidation system does not have soluble in the cytoplasmic components, therefore all its enzymes are collected on the surface of the endoplasmic reticulum. This system includes several proteins that form an electrotransport chain:

- NADP-P450-reductase and cytochrome P450;

- NAD-cytochrome B5-reductase and cytochrome B5;

- steatoryl-CoA desaturase.

The donor of electrons in the overwhelming number of cases is NADP (nicotinamide adenine dinucleotide phosphate). It is oxidized by NADP-P450 reductase, which contains two coenzymes (FAD and FMN), for the acceptance of electrons. At the end of the chain, the PMN is oxidized by P450.

Cytochrome P450

It is an enzyme of microsomal oxidation, a heme-containing protein. Bind oxygen and substrate (usually a xenobiotic). Its name is associated with the absorption of light with a wavelength of 450 nm. Biologists have found it in all living organisms. Currently, more than eleven thousand proteins are included in the cytochrome P450 system. In bacteria, this substance is dissolved in the cytoplasm, and it is believed that this form is the most evolutionarily ancient than human. In our country, cytochrome P450 is a parietal protein fixed on the endoplasmic membrane.

Enzymes of this group are involved in the exchange of steroids, bile and fatty acids, phenols, neutralization of drugs, poisons or drugs.

Properties of microsomal oxidation

The processes of microsomal oxidation have broad substrate specificity, and this, in turn, makes it possible to neutralize a variety of substances. Eleven thousand cytochrome P450 proteins can be folded into more than one hundred and fifty isoforms of this enzyme. Each of them has a large number of substrates. This makes it possible for an organism to get rid of practically all harmful substances that form inside it or come from outside. Developed in the liver, microsomal oxidation enzymes can act both locally and at a considerable distance from this organ.

Regulation of activity of microsomal oxidation

Microsomal oxidation in the liver is regulated at the level of information RNA, or rather its function - transcription. All variants of cytochrome P450, for example, are recorded on a DNA molecule, and in order for it to appear on the EPR, it is necessary to "rewrite" part of the information from DNA to the information RNA. Then, the mRNA is directed to the ribosomes, where protein molecules are formed. The number of these molecules is regulated externally and depends on the volume of substances that need to be deactivated, as well as the availability of essential amino acids.

At the moment, more than two hundred and fifty chemical compounds have been described that activate microsomal oxidation in the body. These include barbiturates, aromatic carbohydrates, alcohols, ketones and hormones. Despite such an apparent diversity, all these substances are lipophilic (soluble in fats), and therefore susceptible to cytochrome P450.