The role of microsomal oxidation in the life of an organism is difficult to overestimate or not to notice. Inactivation of xenobiotics (toxic substances), the breakdown and formation of hormones of the adrenal glands, participation in protein metabolism and the preservation of genetic information - this is only a small known fraction of the problems that are solved due to microsomal oxidation. This is an autonomous process in the body that starts after the trigger substance enters and ends with its elimination.
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. Due to this, the structure of the initial substance changes, and its properties can both be suppressed and strengthened.
Microsomal oxidation allows the transition to a conjugation reaction. This is the second phase of the conversion of xenobiotics, at the end of which the molecules produced inside the body join the existing functional group. Sometimes intermediate substances are formed that cause damage to the liver cells , necrosis and oncological degeneration of tissues.
Oxidase type oxidation
Microsomal oxidation reactions occur outside the mitochondria, and therefore 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 metal atoms with variable valency, such as iron, molybdenum, copper and others, which means that they are able to accept electrons. In the cell, oxidases are located in special vesicles (peroxisomes) that are located on the outer mitochondrial membranes and in the EPR (granular endoplasmic reticulum). The substrate, falling on peroxisomes, loses hydrogen molecules that attach to the water molecule and form peroxide.
There are only five oxidases:
- monoaminooxygenase (MAO) - helps to oxidize adrenaline and other biogenic amines formed in the adrenal glands;
- diaminoxygenase (DAO) - is involved in the oxidation of histamine (a mediator of inflammation and allergies), polyamines and diamines;
- L-amino acid oxidase (i.e. left-handed molecules);
- D-amino acid oxidase (dextrorotatory molecules);
- xanthine oxidase - oxidize adenine and guanine (nitrogenous bases in the DNA molecule).
The value of microsomal oxidase oxidase type is the elimination of xenobiotics and inactivation of biologically active substances. The formation of peroxide, which has a bactericidal effect and mechanical cleansing at the site of damage, is a side effect that occupies an important place among other effects.
Oxidation type oxidation
Oxygenase-type reactions in the cell also occur on the granular endoplasmic reticulum and on the outer shells of the mitochondria. This requires specific enzymes - oxygenases, which mobilize an oxygen molecule from the substrate and introduce it into the oxidized substance. If one oxygen atom is introduced, then the enzyme is called monooxygenase or hydroxylase. In the case of the introduction of two atoms (that is, a whole oxygen molecule), the enzyme is called diaxigenase.
The oxidation reactions of the oxygenase type enter into a three-component multienzyme complex, which is involved in the transfer of electrons and protons from the substrate with subsequent activation of oxygen. This whole process takes place with the participation of cytochrome P450, which will be discussed in more detail.
Examples of oxygenase type reactions
As mentioned above, monooxygenases use only one oxygen atom out of two available for oxidation. The second they attach to two molecules of hydrogen and form water. One example of such a reaction is collagen formation. In this case, vitamin C acts as a donor of oxygen. Prolining hydroxylase takes an oxygen molecule from him and gives it to proline, which, in turn, is included in the procollagen molecule. This process gives strength and elasticity to the connective tissue. When the body is deficient in vitamin C, gout develops. It is manifested by weakness of the connective tissue, bleeding, hematomas, tooth loss, that is, the quality of collagen in the body becomes lower.
Hydroxylases, which transform cholesterol molecules, are another example. This is one of the stages of the formation of steroid hormones, including sex.
Low-specific hydroxylases
These are hydrolases necessary for the oxidation of foreign substances, such as xenobiotics. The meaning of the reactions is to make such substances more malleable for excretion, more soluble. This process is called detoxification, and it occurs mostly in the liver.
Due to the inclusion of a whole oxygen molecule in xenobiotics, the reaction cycle is broken and one complex substance decomposes into several simpler and more accessible for metabolic processes.
Active oxygen species
Oxygen is a potentially hazardous substance, since, in essence, oxidation is a burning process. In the form of an O 2 molecule or water, it is stable and chemically inert, because its electrical levels are filled and new electrons cannot join. But compounds in which oxygen does not have all electrons have a vapor, have a high reactivity. Therefore, they are called active.
Such oxygen compounds:
- In monoxide reactions, superoxide is formed, which is separated from cytochrome P450.
- In oxidase reactions, peroxide anion (hydrogen peroxide) is formed.
- During reoxygenation of tissues that have undergone ischemia.
The strongest oxidizing agent is the hydroxyl radical, it exists in its free form for only a millionth of a second, but during this time it manages to undergo many oxidative reactions. Its peculiarity is that the hydroxyl radical acts on substances only in the place in which it was formed, since it cannot penetrate tissues.
Superoxidion and hydrogen peroxide
These substances are active not only at the site of formation, but also at some distance from them, as they can penetrate through 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 consequence, the genetic apparatus of the cell suffers. The fatty acids that make up the bilipid layer of cell membranes are also oxidized. This affects their permeability, the operation of membrane electrolyte pumps and the location of receptors.
Microsomal oxidation inhibitors are antioxidants. They are found in foods and are produced within the body. The most famous antioxidant is vitamin E. These substances can inhibit microsomal oxidation. Biochemistry describes the interaction between them according to the feedback principle. That is, the more oxidases, the more they are suppressed, and vice versa. This helps maintain a balance between systems and a constant internal environment.
Electric transport chain
The microsomal oxidation system does not have components soluble in the cytoplasm; therefore, all of its enzymes are collected on the surface of the endoplasmic reticulum. This system includes several proteins that form the electric transport chain:
- NADP-P450 reductase and cytochrome P450;
- NAD-cytochrome B5 reductase and cytochrome B5;
- steatoryl CoA desaturase.
In the overwhelming majority of cases, the electron donor is NADP (nicotinamide adenine dinucleotide phosphate). It is oxidized by NADP-P450 reductase, which contains two coenzymes (FAD and FMN), to accept electrons. At the end of the chain, FMN is oxidized using P450.
Cytochrome P450
It is a microsomal oxidation enzyme , a heme-containing protein. It binds oxygen and the substrate (usually a xenobiotic). Its name is associated with the absorption of light with a wavelength of 450 nm. Biologists discovered it in all living organisms. At the moment, more than eleven thousand proteins are described that are part of 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 in humans. Our 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, the neutralization of drugs, poisons or drugs.
Microsomal Oxidation Properties
The processes of microsomal oxidation have a wide substrate specificity, and this, in turn, allows neutralizing a variety of substances. Eleven thousand cytochrome P450 proteins can add up to more than one hundred and fifty isoforms of this enzyme. Each of them has a large number of substrates. This allows the body to get rid of almost all the harmful substances that form inside it or fall from the outside. Produced in the liver, microsomal oxidation enzymes can act both locally and at a considerable distance from this organ.
Regulation of microsomal oxidation activity
Microsomal oxidation in the liver is regulated at the level of messenger 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” some of the information from DNA to messenger RNA. Then the mRNA is sent to the ribosomes, where protein molecules are formed. The number of these molecules is regulated externally and depends on the volume of substances that must be deactivated, as well as on the presence of the necessary amino acids.
At the moment, more than two hundred and fifty chemical compounds that activate microsomal oxidation in the body are described. These include barbiturates, aromatic carbohydrates, alcohols, ketones and hormones. Despite this apparent diversity, all of these substances are lipophilic (soluble in fats), and therefore susceptible to cytochrome P450.