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25PROVITAMINS AND THEIR EFFECT ON THE BODY
RAKHMONOV Akbar
Student of Tashkent Pediatric Medical University akbarrakhmonov0112@gmail.com MUHAMMADOVA Dillora
Student of Tashkent Pediatric Medical University
AHMADOVA Malika
Student of Tashkent Pediatric Medical University
MAHAMADOVA Farzona
Student of Tashkent Pediatric Medical University
d https://doi.org/10.24412/2181-2993-2022-3-50-61
The importance of vitamins cannot be overestimated for the physiological and biochemical processes of the body, not only of humans, but also of all living beings. So in medical practice, vitamin deficiency, hypovitaminosis and hypervitaminosis of certain vitamins that can cause serious harm to health are noted. In addition to true vitamins, there are
ABSTRACT
vitamin-like substances that are involved in such important processes as the respiratory chain of electron transfer, methylation of a number of amino acids and even are part of the enzymes of the MPC. Such substances include ubiquinone, lipoic acid, pangamic acid, orotic acid, inositol, choline and carnitine. The structural and biochemical features, as well as the results of clinical studies, will be given below.
Keywords: Vitamin, electron, in vivo, membrane, mitochondria, reabsorption, metabolism, enzyme, product, deficiency, clinic.
Значение витаминов невозможно переоценить для физиологических и биохимических процессов организма не только человека, но и всех живых существ. Так в медицинской практике отмечают авитаминоз, гиповитаминоз и гипервитаминоз некоторых витаминов, которые могут нанести серьезный вред здоровью. Помимо истинных витаминов существуют витаминоподобные АННОТАЦИЯ вещества, участвующие в таких важных процессах, как дыхательная цепь переноса электронов, метилирование ряда аминокислот и даже входящие в состав ферментов МПК. К таким веществам относятся убихинон, липоевая кислота, пангамовая кислота, оротовая кислота, инозитол, холин и карнитин. Структурные и биохимические особенности, а также результаты клинических исследований будут приведены ниже.
Ключевые слова: витамин, электрон, мембрана, митохондрии, реабсорбция, метаболизм, фермент, продукт, дефицит, клиника.
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INTRODUCTION
Back in 1988, researchers at the National Academy of Medicine officially recognized choline as an essential nutrient in the journal Medical News Today [12]. Choline or vitamin B4 is part of lecithin (part of the liver cell membrane), is a precursor of the neurotransmitter acetylcholine. Choline is widely distributed in eggs, liver, meat products and fish [13]. In the human body, choline can be synthesized in vivo from serine after decarboxylation and methylation reactions [14].
DISCUSSION AND RESULTS
Choline participates in DNA methylation through a modified substance trimethylglycine (betaine). A source of methyl groups, the S-adenosylmethionine molecule, is synthesized on the basis of betaine. The main component of lecithin is phosphatidylcholine, one of the phospholipids of the cell membrane. This function is used in medical practice as a hepatoprotective substance. Thus, choline accelerates the structural recovery of damaged liver tissues under toxic or infectious influences, improving the state of bile and exerting a number of other positive effects [15,16]. In neurons, choline reacting with acetyl-CoA with the help of the enzyme choline acetyltransfer gives the product acetylcholine, which is one of the most common mediators of the body [17]. Acetylcholine itself is a neurotransmitter in both the peripheral and central nervous systems. Acetylcholine being exposed to its receptor (nicotine or muscarinic) activates it. Nicotine receptors located on smooth muscles and in the central nervous system change the permeability of the cell to sodium, potassium and chlorine ions. Moreover, muscarinic receptors localized in the central nervous system, myocardium, lungs and sweat glands do not change ionic conductivity, but initiate an intracellular signal through the G-protein chain. The S-adenosylmethionine molecule (SAM, SAMe, SAM-e, ademethionine) is a coenzyme involved in methyl group transfer reactions. S-adenosyl methionine is formed from adenosine triphosphate (ATP) and methionine by the enzyme methioninadenosyltransferase and is an intermediate product. The methionine transformation cycle includes homocysteine, methionine, S-adenosylmethionine and S-adenosylhomocysteine [17].
Choline deficiency is extremely rare, as it is present in many products and is available for entry into the body. However, a deficiency can occur in pregnant and lactating women, in children during critical periods of growth and in utero, in athletes and vegans, in addition, a large amount of choline is consumed in students. On average, the norm of vitamin B4 is 450-500mg per day [18].
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Ubiquinone
Ubiquinone (coenzyme Q, coenzyme Q10) is a derivative of benzoquinone; it contains a quinoid group and 10 isoprenyl groups, which is reflected in one of the names of the substance — coenzyme Q10.
Vitamin-like substance is synthesized in the body from the amino acid tyrosine with the participation of vitamins B2, B3, B6, B12, C, folic and pantothenic acids, as well as a number of trace elements. This is a complex, multi-stage process regulated by several enzyme systems. [19]
The amount of CoQ10 that is naturally found in food is much lower than in supplements. Good food sources of CoQ10 include cold-water fish such as tuna, salmon, mackerel and sardines, vegetable oils and meat. [20]
Coenzyme Q10 (CoQ) is an endogenous lipophilic quinone ubiquitously present in biological membranes, where it acts as a cofactor of mitochondrial respiratory complexes supporting cellular bioenergetics. Its reduced form (ubiquinol) has antioxidant activity as an active radical scavenger, and synergistically supports a larger cellular antioxidant network. By reducing the lipid peroxidation of low-density lipoprotein (LDL) particles, which contributes to atherosclerosis, CoQ treatment has a positive effect on health in relation to cardiovascular diseases. The antioxidant function of CoQ is particularly important for the plasma membrane by reducing the content of vitamins C and E and preventing ceramide-mediated apoptosis, an important regulator of life expectancy in the context of normal aging. These two functions, bioenergetics and antioxidant, characterized the studies of Coenzyme Q in the second half of the 20th century, while in the first decades of the new millennium, studies revealed new functions of Coenzyme Q, emphasizing its role in the modulation of gene expression, mitochondrial function and signal transmission, with important consequences in the aging process and cell death [21]. For these reasons, CoQ seems to be suitable for use in the treatment of various diseases. Here we present the latest advances in the treatment of human diseases with 10 and slowing down the aging process, as well as highlight new strategies aimed at slowing the progression of chronic diseases with CoQ10 supplements [21].
Ubiquinone deficiency is of particular importance in a number of diseases. Clinical studies have established that the development of many metabolic and dystrophic diseases, pathology of the immune system, premature aging, overweight are closely related to a lack of energy formation in the body and damage to cellular energy generators in which CoQ is an integral component. Also, a decrease in the functionality of the heart, muscles, skin and other organs) is associated with a decrease in the concentration of ubiquinone. Some degenerative diseases
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(atherosclerosis, Parkinson's disease, Alzheimer's disease and rare genetic abnormalities) are associated with a deficiency of ubiquinone synthesis [21,22].
Inositol, also called cyclohexangexol, is any of several stereoisomeric alcohols similar in molecular structure to simple carbohydrates. There are nine forms of inositol; the most famous of the inosites is myo-inositol, named after its presence in the muscle tissue from which it was first obtained in 1850. Myo-inositol is one of the stereoisomers of sugar alcohol C6, which belongs to the inositol family. It is a precursor of inositol triphosphate, acting as an intracellular secondary messenger and regulating a number of hormones, such as thyroid-stimulating hormone, follicle-stimulating hormone (FSH) and insulin. Myoinositol is usually obtained from grains in which it is present in the form of hexaphosphate, phytic acid [23,24]. Inositol derivatives are rarely found in modern diets. However, animal products include the highest content of inositol, in particular: kidney, brain. Other products containing inositol include almonds, walnuts, and citrus fruits, except lemon [25].
Myo-inositol (sometimes-called vitamin B8) is one of the endogenous human metabolites that has a significant impact on the functioning of all tissues, including the reproductive system. Recall that in postgenomic pharmacology, the effects of any molecule are considered in the context of effects on the genome (the totality of all genes of a given organism), transcriptome (the totality of all mRNA transcripts synthesized during genome expression), proteome (the totality of all proteins synthesized on the basis of mRNA transcriptome), metabolome (the totality of all metabolites found in cells and fluids of this organism) and the reaction, i.e. the totality of all chemical reactions occurring in the cells and tissues of the body. Myo-inositol is used for the sequential synthesis of various inositol phosphate derivatives involved in the transmission of intracellular signals from insulin receptors, the breakdown of fats, the reduction of triglycerides, cholesterol in the blood and the transmission of signals from reproductive hormone receptors, which has a profound effect not only on the metabolome, but also on the reactome, proteome, transcriptome of cells [26].
Insufficient intake of myo-inositol into the body or its insufficient synthesis has been underestimated for a long time. When it was found that in a healthy person, myo-inositol is synthesized in vivo in the kidneys in an amount of several grams per day, myo-inositol began to be called a vitamin-like substance. However, the conditions for the synthesis of a sufficient amount of myo-inositol in the kidneys are their perfect health and a sufficient number of nephrons. Diseases such as renal hypertension, pyelonephritis, glomerulonephritis, tubulopathy, nephrosis, diabetic
Inositol
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nephropathy, toxic kidney damage, as well as drug load on the kidneys dramatically reduce the synthesis of myo-inositol in the kidneys and increase the loss of this micronutrient in the urine. Accordingly, if the patient has certain disorders of renal function, then correction of the resulting deficiency of myo-inositol is necessary, the availability of which is important for the functioning of a woman's reproductive system [26]. As a result, myo-inositol has a positive effect on the cardiovascular system, immunity, has a neurotrophic and neuroprotective effect, participates in the metabolism of sugars, and affects the functioning of the reproductive system. Violation or deficiency of vitamin B8 has a negative effect, changing the functioning of the above systems [27].
Pangamic acid
Krebs, who gave the name to this substance, discovered Pangamic acid (pangomat, vitamin B15) in apricot. From the point of view of biochemistry, this substance is not included in the number of vitamins, although it does not participate in plastic metabolism. The fact is that vitamin-like B15 deficiency is practically not observed, and any specific diseases [15] do not accompany its change in quantity from normal limits.
In his writings, Krebs described and prescribed pangamic acid as a substance for the treatment of asthma, dermatitis, as well as pain in joints and nerves [15]. His scientific works were not supported by long-term clinical observations. It should be mentioned that research on pangamat was conducted in the USSR, but the scientific works written at that time do not have sufficient authority. Later it was proposed as an antitumor, cardiotonic and antihypoxic drug, but none of these points was also clinically justified [29,30]. Back in 1980, this substance was indicated as carcinogenic. Now, the import of drugs containing pangamic acid is prohibited in many countries [30]. In Canada, all products containing B15 are generally prohibited. A number of authors indicate this substance as a "quack remedy". Nevertheless, all research on pangamate was conducted only in the 20th century; it is likely that this substance has not been sufficiently studied.
Lipoic acid
Lipoic acid (often called a-lipoic acid), also known as thioctic acid, is a natural organosulfur compound synthesized by plants and animals, including humans [31]. Alpha-lipoic acid is a disulfide derivative of octanoic acid. It is considered both fat-and water-soluble, so it can penetrate into any tissues of the body, exerting an antioxidant effect not only outside, but also inside the cell. In the human body, lipoic acid is synthesized only in a small amount. That is why many turn to certain foods or supplements to optimize their consumption. Animal products such as red meat and
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meat offal are excellent sources of alpha lipoic acid, but plant foods such as broccoli, tomatoes, spinach also contain it.
ALA is a natural coenzyme of the mitochondria of a multienzyme complex that catalyzes the oxidative decarboxylation of alpha-keto acids, such as pyruvate and alpha-ketoglutarate. LC plays a direct role in the metabolism of lipids and arachidonic acid to prostaglandin N. It is a direct antioxidant protecting DNA, proteins and lipids of cells from reactive oxygen species. It also potentiates the antioxidant properties of vitamin C, glutathione and ubiquinone. In addition, experiments have shown that it protects cells from the effects of free iron and copper ions.
The structural formula and properties of ALA were discovered in 1951, in the same year its first clinical trials were conducted, the use of alpha-lipoic acid in humans was started in 1970. Early studies on the use of ALA were conducted against the background of insufficient understanding of the mechanisms of its action and concerned mainly lipid and carbohydrate metabolism [32,33]. Clinical trials evaluating the effect of lipoic acid on obesity, diabetes, diabetic neuropathy, cardiovascular diseases and Alzheimer's disease have shown that dietary supplements of lipoic acid have a beneficial effect on disorders of lipid metabolism in plasma, inflammatory reactions, and oxidative stress and stabilize cognitive functions. Reduced in patients with Alzheimer's disease. Clinical trials have shown neuroprotective effects of lipoic acid provided by oral administration [34].
LC is sequentially synthesized de novo in mitochondria from 8-carbohydrate octane fatty acid using an acyl carrier protein. The introduction of 2 sulfur atoms at positions 6 and 8 of the octanoyl part occurs with the participation of lipoilsynthase, an enzyme containing iron-sulfur clusters - sulfur donors 2 thiol (sulfur) groups can be oxidized or reduced. The oxidation of the dihydrolipoyl part is catalyzed by dihydrolipoamide dehydrogenase. The results of in vitro studies have shown that in cells, LC is reduced to dihydrolipoic acid (DLC), which is then rapidly exported from them [35]. It is generally believed that a person is able to synthesize a sufficient amount of lipoic acid for himself, but with fermentopathies of the above enzymes, there may be a deficiency state with a decrease in the antioxidant and anti-toxic properties of the body [35].
Orotic acid
Orotic acid — 2,6-dioxypyrimidine-4-carboxylic acid — is a derivative of pyrimidine, more precisely uracil. It was first isolated by Biscaro and Belloni from cow colostrum back in 1905 . Orotic acid got its name from the Greek word hos — serum [36]. In the human body, orotic acid is synthesized in the liver from aspartate
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and carbamoyl phosphate. Food sources rich in orotic acid are dairy products, carrots and beets [36].
Orotic acid (vitamin B13) is necessary for the fixation of magnesium on ATP in the cell, which leads to the activation of ATP-az and the launch of energy metabolism. Orotic acid has its own metabolic activity, is one of the metabolic precursors of pyrimidine nucleotides, and is necessary for the normal course of anabolic processes. At the myocardial level, the therapeutic activity of orotic acid is expressed in an increase in protein synthesis and ATP. Athletes successfully use the anabolic properties of orotic acid, for example, in order to improve performance. It has been established that orotic acid maintains cholesterol in a colloidal state, which possibly prevents its accumulation in the vascular wall and the progression of atherosclerosis. Orotic acid plays a central role in the metabolism of folic acid, vitamin B12 and can increase the transport of minerals through the cell membrane. Being a key link in the biosynthesis of pyrimidines, orotic acid plays a protective role in maintaining the energy balance of the damaged myocardium, stimulating the synthesis of glycogen and ATP [37]. Vitamin B13 and its derivatives are nutrients for the microbiota. For example, the genomes of lactic acid bacteria Lactobacillus contain genes encoding special proteins for the transport and biotransformation of orotic acid. Vitamin B13 participates in many major metabolic processes, in particular: glucose processing; maintenance of adenosine triphosphate reserves; ribose synthesis; creation of carnosine reserves in skeletal muscles and myocardium; growth and development of cells and tissues, for example, muscle (due to RNA synthesis); activation of contractile capabilities of muscle tissues [38].
L-carnitine is a lysine derivative, was first obtained from meat for the first time (camis), and therefore got its name. In the last decade, it has been widely studied as a promising broad-spectrum drug [1]. In humans, L-carnitine homeostasis, that is, it occurs in vivo in the liver, is ensured by multistage reactions of the amino acids lysine and methionine, its absorption from food and modification in the kidneys. L-carnitine in high concentrations in large quantities is found in meat and dairy products. Bioavailability at a high level [2,3].
Carnitine is of great importance in tissues and organ systems that use fatty acids for the synthesis of ATP, such as striated muscles, cardiomuscles. One of the main functions is the transfer of long—chain fatty acids from the intermembrane space through the inner membrane into the mitochondrial matrix for the inclusion of acids in P-oxidation [1]. This mechanism is carried out with the help of special
Carnitine
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mitochondrial enzymes, so some enzymes catalyze the acid addition reaction to L-carnitine, while others transport the product to the matrix [4].
In healthy people without metabolic disorders, as well as in the absence of special protein diets, there is no deficiency of this substance. Signs of L-carnitine deficiency were not found even in people with a strict vegetarian diet [5]. Nevertheless, newborns, especially premature babies, are often born with low L-carnitine reserves.
Generalized form of primary L-carnitine deficiency. A rare autosomal recessive disorder caused by mutations in the gene for the L-cornitine transport protein OCTN2, leading to low absorption in enterocytes and decreased renal reabsorption. So the body not only cannot assimilate through food, but also retain synthesized in vivo [6,7,8]. Clinical features have been manifested since early childhood and are characterized by low levels of L-carnitine in the liquid part of the blood, progressive cardiomyopathy, general myopathy, a decrease in blood glucose and hypoammonemia [1,6,8]. Without treatment, the outcome of primary systemic L-carnitine deficiency is unfavorable. The myopathic form of primary deficiency — L-carnitine - in this case, the deficiency is observed only in skeletal and cardiac muscles. The clinical picture is less pronounced than in generalized. The main symptoms of muscle pain and weakness, manifested in childhood. Secondary L-carnitine deficiency may be hereditary or acquired. A hereditary defect may be in the exchange of propionic acid or an acylCoA dehydrogenase defect [9]. This can lead to the accumulation of organic acids, which in combination with carnitine will be filtered into the urine. In addition, the dysfunction of the proximal convoluted tubules may also be deficient. There is also a disadvantage in the chronic administration of antibiotics based on pivolate. Since pivolate is structurally a fatty acid, which is excreted by the kidneys together with carnitine during reactions [10,11]. Deficiency is noted when the value of L-carnitine in plasma is less than 20 mmol/l [9].
CONCLUSION
The effect of vitamins on the body cannot be underestimated. Without them, a huge number of enzymes of carbohydrate, lipid and protein synthesis/decomposition will not be active [39,41]. There are also steroid vitamins that are able to activate their specific receptors on the nuclei of cells capable of expressing more than 200 genes [40]. Clinical studies and the appointment of dietary supplements with vitamin molecules create a myth that there is no more important vitamins for the health of the body. However, as it was shown in this review, the functional values of provitamins from the point of view of biochemistry, pharmacology and clinic must necessarily be
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disassembled in order to carry out the correct method of diagnosis and prescribing recommendations.
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