Vitamin A: Metabolism
Vitamin A is absorbed similarly to lipids - this process involves the emulsification and hydrolysis of its esters in the lumen of the gastrointestinal tract, the adsorption and transport of it into the cells of the mucous membrane, the re-sterilization of retinol in them and the subsequent intake of vitamin A in the liver as part of chylomicrons.
Absorption of vitamin A occurs mainly in the small intestine, mainly in its upper part. Vitamin A under normal conditions, when consumed in physiological doses, is absorbed almost completely. However, the completeness of absorption of vitamin A is largely dependent on its amount (in particular, as the dose increases, the absorption decreases proportionally). This decrease, apparently, is associated with increased oxidation and a violation of the mechanisms of active absorption of vitamin A in the intestine, which is due to adaptive mechanisms aimed at preventing the body from vitamin-induced intoxication.
Emulgation of retinol is a necessary step in the process of its absorption in the gastrointestinal tract. In the presence of lipids and bile acids, free vitamin A is absorbed by the intestinal mucosa, and its esters - after hydrolysis by enzymes of the pancreas and mucous membrane of the small intestine (hydrolase esters of carboxylic acids).
Up to 40% of carotene is absorbed unchanged. Assimilation of carotene is promoted by high-grade proteins in the diet. Improves the assimilation of ß-carotene from boiled, homogenized products together with emulsions of fats (especially unsaturated fatty acids) and tocopherols. β-carotene in the intestinal mucosa undergoes oxidation through a central double bond involving a specific enzyme of the small intestine carotin dioxygenase (carotinase), with the formation of 2 molecules of active retinal. The activity of carotinase is stimulated by thyroid hormones. With hypothyroidism, this process can be disturbed, which leads to the development of carotenemic pseudo-jaundice.
In children under 1 year of age, carotinase is inactive, so the absorption of carotene is poor. Inflammations of the intestinal mucosa and cholestasis lead to the fact that carotenes and vitamin A are poorly absorbed.
In the intestinal mucosa on the inner surface of the villi, vitamin A is similar to triglycerides undergoing resynthesis, forming esters with fatty acids. This process is catalyzed by the enzyme retinol synthetase. The newly synthesized ether of retinol enters the lymph and is transported to the liver in the chylomicrons (80%), where it is captured by stellate reticuloendotheliocytes and then by hepatocytes. The etheric form - retinyl palmitate is accumulated in the liver cells, and its stock in an adult is enough for 23 years. Retinol esterase releases retinol, which is carried in the blood by trans-retinethin. Release of retinol by the liver is a zinc-dependent process. The liver is not only the main depot of vitamin A, but also the main site for the synthesis of "retinol-binding protein" (RSB), with which vitamin A specifically binds in the blood. RSB refers to the prealbumin fraction, its molecular weight is 21 kD. The concentration of PCB in human plasma is 4 mg per ml. RSB in connection with retinol enters the complex with a protein of much higher molecular weight - thyroxine-binding prealbumin and is transported as a complex complex: vitamin A + retinol-binding protein + thyroxine-binding prealbumin.
The complex of vitamin A and RSB has a significant physiological significance, which consists not only in solubilization of water-insoluble retinol and its delivery from the depot (liver) to the organs of the body, but also in protecting the unstable free form of the retinol molecule from chemical decomposition (eg, vitamin A becomes stable to the oxidative effects of alcohol dehydrogenase of the liver). RSB has a protective function in cases of high doses of vitamin A in the body, which is manifested in the protection of tissues from the toxic, in particular the membrane, effect of the vitamin. Intoxication with vitamin A develops when vitamin A in plasma and membranes is not in combination with RSB, but in another form.
In addition to the liver, vitamin A is also deposited in the retina, somewhat less in the kidneys, heart, fat stores, lungs, in the lactating mammary gland, in the adrenal glands and other endocrine glands. Intracellularly, vitamin A is localized predominantly in the microsomal fraction, mitochondria, lysosomes, in cell membranes and organelles.
In tissues, vitamin A is converted into retinyl palmitate, retinyl acetate (esters of retinol with palmitic and acetic acids) and retinyl phosphate (phosphoric ether of retinol).
Part of retinol in the liver (vitamin A - alcohol) is converted into retinal (vitamin A-aldehyde) and retinoic acid (vitamin A-acid), that is, oxidation of the alcohol group, vitamers A1 and A2, respectively, into aldehyde and carboxyl.
Vitamin A and its derivatives are found in the body in a transconfiguration (linear form), with the exception of the retina, where the cisomeris (11-cis retinol and 11-cisrethinal folded form) undertake.
Biological activity is possessed by all forms of vitamin A: retinol, retinal, retinoic acid and their ether derivatives.
Retinal, retinoic acid are secreted by hepatocytes in the bile in the form of glucuronides, retinol glucuronide is excreted in the urine.
Elimination of retinol is slow, so when applied as a drug, it is possible to switch to the development of an overdose.
How does vitamin A affect the body?
Vitamin A restores the shape and strength of the nails, it promotes the healing of wounds, thanks to it the hair grows faster, they look healthier and shiny.
Vitamin A - an antioxidant, it fights with aging, strengthens the immune system, increases resistance to viruses and pathogens.
Vitamin A is very good for the reproductive system of men and women, increases the activity of producing sex hormones, and also struggles with such a serious disease as night blindness (hemeralopathy).
Biological functions of vitamin A
Vitamin A have a wide range of biological effects. In the body, vitamin A (its active form of retinal) controls the following processes:
- Regulates the normal growth and differentiation of the cells of the developing organism (embryo, young body).
- Regulates the biosynthesis of glycoproteins of external cytoplasmic membranes that determine the level of cellular differentiation processes.
- Increases the synthesis of protein in cartilage and bone tissue, which determines the growth of bones and cartilage in length.
- Stimulates epithelization and prevents excessive keratinization of the epithelium of hyperkeratosis. Regulates the normal function of a single-layered flat epithelium, which performs a barrier role.
- Increases the number of mitoses in epithelial cells, vitamin A regulates division and differentiation in rapidly proliferating (dividing) tissues, prevents accumulation of keratogialin (cartilage, bone tissue, epithelium of skin and mucous membranes, spermatogenic epithelium and placenta) in them.
- Promotes the synthesis of RNA and sulfated mucopolysaccharides, which play an important role in the permeability of cellular and subcellular, especially lysosomal membranes.
- Due to lipophilicity, it is integrated into the lipid phase of membranes and has a modifying effect on membrane lipids, controls the rate of chain reactions in the lipid phase, can form peroxides, which in turn increase the oxidation rate of other compounds. Supports the antioxidant potential of various tissues at a constant level (this explains the use of vitamin A in cosmetology, especially in preparations for fading skin).
- Having a large number of unsaturated bonds, vitamin A activates redox processes, stimulates the synthesis of purine and pyrimidine bases, participates in the energy supply of metabolism, creating favorable conditions for the synthesis of ATP.
- Participates in the synthesis of albumin and activates the oxidation of unsaturated fatty acids.
- Participates in the biosynthesis of glycoproteins, as a lipid carrier through the cell membrane of hydrophilic residues of mono- and oligosaccharides to the sites of their connection with the protein base (to the endoplasmic reticulum). In turn, glycoproteins have broad biological functions in the body and can be enzymes and hormones, participate in antigen-antibody interactions, participate in the transport of metals and hormones, and in blood coagulation mechanisms.
- Participates in the biosynthesis of mucopolysaccharides that make up mucus, performing a protective action.
- Increases the resistance of the body to infection, vitamin A enhances the formation of antibodies and activates phagocytosis.
- It is necessary for normal cholesterol metabolism in the body:
- regulates the biosynthesis of cholesterol in the intestine and its absorption, with a lack of vitamin A, the absorption of cholesterol is accelerated and accumulation occurs in the liver.
- participates in the biosynthesis of hormones of the adrenal cortex from cholesterol, vitamin A stimulates the synthesis of hormones, with a lack of vitamin reduces the nonspecific reactivity of the organism.
- It inhibits the formation of thyroidiborins and is an antagonist of iodothyronines, suppresses the function of the thyroid gland, and the thyroxine itself contributes to the breakdown of the vitamin.
- Vitamin A and its synthetic analogs can inhibit the growth of some tumors. Antitumor effect is associated with stimulation of immunity, activation of humoral and cellular immune response.
Retinoic acid is involved in stimulating the growth of only bones and soft tissues:
- Regulates the permeability of cell membranes, increasing their stability, by controlling the biosynthesis of their components, in particular individual glycoproteins, and thus has an effect on the barrier function of the skin and mucous membranes.
- Stabilizes membranes of mitochondria, regulates their permeability and activates enzymes of oxidative phosphorylation, biosynthesis of coenzyme Q.
Vitamin A has a wide range of biological effects. It promotes growth and development of the body, differentiation of tissues. And it also provides a normal function of the epithelium of the mucous membranes and skin, increases the resistance of the organism to infections, participates in the processes of photoreception and reproduction.
The most widely known function of vitamin A in the mechanism of night vision. He participates in the photochemical act of sight by forming a pigment of rhodopsin, capable of detecting even minimal light, which is very important for night vision. More Egyptian doctors in 1500 BC. E., described the signs of "chicken blindness" and as a treatment prescribed, there is a liver of a bull. Not knowing about vitamin A, relying on the empirical knowledge of that time.
First of all, vitamin A is a structural component of cell membranes, therefore one of the components of its functions is its participation in the processes of proliferation and differentiation of different types of cells. Vitamin A regulates the growth and differentiation of cells in the embryo and the young body, as well as the division and differentiation of rapidly proliferating tissues, primarily epithelial cells, especially the epidermis and glandular epithelium, which produces a mucous secret, by controlling the synthesis of cytoskeleton proteins. Lack of vitamin A leads to a violation of the synthesis of glycoproteins (more precisely, the reactions of glycosylation, that is, the attachment of the carbohydrate component to the protein), which is manifested by the loss of the protective properties of the mucous membranes. Retinoic acid, having a hormone-like action, regulates the expression of the genes of some growth factor receptors, while it prevents metaplasia of the glandular epithelium in flat keratinizing.
If there is little vitamin A, keratinization of the glandular epithelium of various organs occurs, which disrupts their function and contributes to the occurrence of certain diseases. This is due to the fact that one of the main functions of barrier protection - the clearance mechanism does not cope with the infection, as the maturation process and physiological desquamation are disrupted, as well as the secretion secretion process. All this leads to the development of cystitis and pyelitis, laryngotraheronkitis and pneumonia, skin infections and other diseases.
Vitamin A is necessary for the synthesis of chondroitin sulfates of bone and other connective tissue, with its deficiency, bone growth is impaired.
Vitamin A takes part in the synthesis of steroid hormones (including progesterone), spermatogenesis, is a thyroxine antagonist - the hormone of the thyroid gland. In general, at present, much attention is paid in the world literature to vitamin A derivatives - retinoids. It is believed that their mechanism of action is similar to steroid hormones. Retinoids act on specific receptor proteins in the cell nuclei. Further, such a ligandreceptor complex binds to specific regions of DNA that control the transcription of special genes.
, , , , , , , , , , , , 
The antioxidant effect of vitamin A
Vitamin A and, especially, carotenoids are the most important components of the body's antioxidant defense. The presence of conjugated double bonds in the molecule vitamin A promotes its interaction with free radicals of various types, including free oxygen radicals. This important feature of the vitamin allows us to consider it an effective antioxidant.
The antioxidant effect of retinol is also manifested in the fact that the vitamin significantly enhances the antioxidant effect of vitamin E. Together with tocopherol and vitamin C, it activates the incorporation of selenium into the composition of glutathione peroxidase (an enzyme that neutralizes lipid peroxide). Vitamin A helps maintain SH groups in the reduced state (SH groups of a diverse class of compounds also have an antioxidant function). In particular, preventing the oxidation of SH-containing proteins and the formation of transverse SS-cross-links in keratin in them, vitamin A thereby reduces the degree of keratinization of the epithelium (increased keratinization of the skin leads to the development of dermatitis and early aging of the skin). However, vitamin A can manifest itself as a pro-oxidant, as it is easily oxidized by oxygen with the formation of highly toxic peroxide products. It is believed that the symptoms of hypervitaminosis A are due to its prooxidant effect on biomembranes, especially the process of lipid peroxidation in lysosomal membranes, to which vitamin A shows a pronounced tropicity. Vitamin E, protecting the unsaturated double bonds of retinol from oxidation and the formation, as a result, of free radicals of the retinol itself, interferes with the manifestation of its prooxidant properties. It is also necessary to note the role of ascorbic acid synergistic with tocopherol in these processes.
The antioxidant effect of vitamin A and β-carotene plays an important role in the prevention of heart and arterial diseases, vitamin A has a protective effect in patients with angina pectoris, and also increases the content of "useful" cholesterol (HDL) in the blood. They protect the membranes of brain cells from the destructive effect of free radicals, while β-carotene neutralizes the most dangerous types of free radicals: polyunsaturated radicals and oxygen radicals. Being powerful antioxidants, vitamin A is a means of preventing and treating cancer, in particular, preventing the reappearance of the tumor after surgery.
The most powerful antioxidant effect is the carotenoid-reservein contained in red wine and peanuts. Lycopene, which is rich in tomatoes, differs from all carotenoids in pronounced tropism to adipose tissue and lipids, it has an antioxidant effect on lipoproteins, some antithrombogenic effect.
In addition, it is the most "strong" carotenoid in terms of protection against cancer, especially breast, endometrial and prostate cancer.
Lutein and zeaxentin are the main carotenoids that protect our eyes: they help prevent cataracts, and also reduce the risk of macular degeneration, which in every third case is the cause of blindness. Vitamin A vitamin deficiency is accompanied by keratomalacia.
Vitamin A and immunotropic action
Vitamin A is essential for the proper functioning of the immune system and is an integral part of the infection control process. The use of retinol increases the barrier function of the mucous membranes. Due to the accelerated proliferation of cells of the immune system, the phagocytic activity of leukocytes and other factors of nonspecific immunity increases. β-carotene significantly increases the activity of macrophages, since they contain specific peroxide processes that require a large amount of antioxidants. Macrophages in addition to phagocytosis, carry out the presentation of the antigen and stimulate the function of lymphocytes. There are many publications on the effect of β-carotene on the increase in the number of T-helpers. The greatest effect is shown in people (people and animals) experiencing stress (improper diet, disease, elderly age). In completely healthy organisms, the effect is often minimal or absent. This is due, inter alia, to the elimination of peroxide radicals inhibiting the proliferation of T cells. By a similar mechanism, vitamin A stimulates and produces antibodies by plasma cells.
The immune activity of vitamin A is also associated with its effect on arachidonic acid and its metabolites. It is assumed that vitamin A suppresses the production of arachidonic acid products (refers to omega-fatty acids), thereby inhibiting the production of prostaglandin E2 (a lipid physiologically active substance). Prostaglandin E2 is a suppressor of NK cells, reducing its content, betakarotin enhances the activity of NK cells and stimulates their proliferation.
It is believed that vitamin A protects against colds, flu and respiratory tract infections, digestive tract, urinary tract. Vitamin A is one of the main factors responsible for the fact that children in the more developed countries are much easier to tolerate such infectious diseases as measles and chicken pox, whereas in countries with a low standard of living, the death rate from these "harmless" viral infections is much higher. Vitamin A prolongs life even for people with AIDS.
Vitamin A: special properties
Vitamin A almost does not lose its properties during heat treatment, but in combination with air, during long-term storage, it collapses. When cooking, 15 to 30% of vitamin A is lost.
From the way vegetables are grown with vitamin A, its content in these products depends. For example, if the soils are too poor, then vitamin A in them is much less. If vegetables are grown with a high content of nitrates, they have the property of destroying vitamin A - both in the body and in the plants themselves.
Vegetables, which are grown in winter, have 4 times less vitamin A than those grown in the summer. Greenhouse cultivation also depletes vegetables for vitamins by about 4 times. If the vegetables do not have vitamin E, then vitamin A will be absorbed much worse.
Milk (natural) contains a lot of vitamin A. But only if the cows are fed plants grown on fertile soils and if their diet contains vitamin E. It protects vitamin A from destruction.
To get vitamin A in the form of carotene from plant foods, you need to destroy the walls of cells behind which carotene is contained. Therefore, these cells need to be ground. This can be done by chewing, grinding with a knife or by cooking. Then vitamin A is well absorbed and well absorbed into the intestine.
The softer the vegetables, from which we take carotene, the better vitamin A will be absorbed.
The best source of carotene, from which it is immediately absorbed, is fresh. True, they need to drink immediately, because in combination with oxygen, the useful properties of fresh are destroyed. Fresh should be drunk no earlier than 10 minutes.