Water soluble  vitamins: structure, properties, biological role

 

 Thiamin (Vitamin B1)

 Thiamin (also spelled thiamine) is a water-soluble B vitamin, previously known as vitamin B1 or aneurine. Isolated and characterized in the 1930s, thiamin was one of the first organic compounds to be recognized as a vitamin. Thiamin occurs in the human body as free thiamin and as various  phosphorylated forms: thiamin monophosphate (TMP), thiamin triphosphate (TTP), and thiamin pyrophosphate (TPP), which is also known as thiamin diphosphate.

Deficiency

Beriberi, the disease resulting from severe thiamin deficiency, was described in Chinese literature as early. Thiamin deficiency affects the cardiovascular, nervous, muscular, and  gastrointestinal systems. Beriberi has been termed dry, wet, or cerebral, depending on the systems affected by severe thiamin deficiency.

Food sources

 

A varied diet should provide most individuals with adequate thiamin to prevent deficiency. In the U.S. the average dietary thiamin intake for young adult men is about 2 mg/day and 1.2 mg/day for young adult women. A survey of people over the age of 60 found an average dietary thiamin intake of 1.4 mg/day for men and 1.1 mg/day for women. However, institutionalization and poverty both increase the likelihood of inadequate thiamin intake in the elderly.Whole grain cereals, legumes (e.g., beans and lentils)nuts, lean pork, and yeast are rich sources of thiamin. Because most of the thiamin is lost during the production of white flour and polished (milled) rice, white rice and foods made from white flour (e.g., bread and pasta) are fortified with thiamin in many Western countries. A number of thiamin-rich foods are listed in the table below along with their thiamin content in milligrams (mg). For more information on the nutrient content of foods, search the  USDA food composition database.

 

Riboflavin (Vitamin B2)

 Riboflavin is a water-soluble B vitamin, also known as vitamin B2. In the body, riboflavin is primarily found as an integral component of the coenzymes, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). Coenzymes derived from riboflavin are termed flavocoenzymes, and  enzymes that use a flavocoenzyme are called flavoproteins.

 Living organisms derive most of their energy from oxidation-reduction (redox) reactions, which are processes that involve the transfer of electrons. Flavocoenzymes participate in redox reactions in numerous metabolic pathways. Flavocoenzymes are critical for the  metabolism of carbohydrates, fats, and proteins. FAD is part of the  electron transport (respiratory) chain, which is central to energy production. In conjunction with  cytochrome P-450, flavocoenzymes also participate in the metabolism of drugs and toxins.

Glutathione reductase is a FAD-dependent enzyme that participates in the  redox cycle of glutathione. The glutathione redoxcycle plays a major role in protecting organisms from  reactive oxygen species, such as hydroperoxides. Glutathione reductaserequires FAD to regenerate two molecules of reduced glutathione from oxidized glutathione. Riboflavin deficiency has been associated with increased oxidative stress. Measurement of glutathione reductase activity in red blood cells is commonly used to assess riboflavin nutritional status.

Glutathione peroxidase, a selenium-containing enzyme, requires two molecules of reduced glutathione to break downhydroperoxides (see diagram).

Xanthine oxidase, another FAD-dependent enzyme,  catalyzes the oxidation of hypoxanthine and xanthine to uric acid. Uric acid is one of the most effective water-soluble  antioxidants in the blood. Riboflavin deficiency can result in decreased xanthine oxidaseactivity, reducing blood uric acid levels.

Deficiency

 

Ariboflavinosis is the medical name for clinical riboflavin deficiency. Riboflavin deficiency is rarely found in isolation; it occurs frequently in combination with deficiencies of other water-soluble vitamins. Symptoms of riboflavin deficiency include sore throat, redness and swelling of the lining of the mouth and throat, cracks or sores on the outsides of the lips (cheliosis) and at the corners of the mouth (angular stomatitis), inflammation and redness of the tongue (magenta tongue), and a moist, scaly skin inflammation (seborrheic dermatitis). Other symptoms may involve the formation of blood vessels in the clear covering of the eye (vascularizationof the cornea) and decreased red blood cell count in which the existing red blood cells contain normal levels of hemoglobin and are of normal size (normochromic normocytic anemia). Severe riboflavin deficiency may result in decreased conversion of vitamin B6 toits  coenzyme form (PLP) and decreased conversion of tryptophan to niacin (see Nutrient Interactions).

Food sources

 

Most plant and animal derived foods contain at least small quantities of riboflavin. In the U.S., wheat flour and bread have been enriched with riboflavin (as well as thiamin, niacin, and iron) since 1943. Data from large dietary surveys indicate that the average intake of riboflavin for men is about 2 mg/day and for women is about 1.5 mg/day; both intakes are well above the RDA. Intake levels were similar for a population of elderly men and women (1). Riboflavin is easily destroyed by exposure to light. For instance, up to 50% of the riboflavin in milk contained in a clear glass bottle can be destroyed after two hours of exposure to bright sunlight. Some foods with substantial amounts of riboflavin are listed in the table below along with their riboflavin content in milligrams (mg). For more information on the nutrient content of foods, search the  USDA food composition database.

Niacin (Vitamin B5)

   

Niacin exists in two forms, nicotinic acid and nicotinamide. Both forms are readily absorbed from the stomach and the small intestine. Niacin is stored in small amounts in the liver and transported to tissues, where it is converted to coenzyme forms. Any excess is excreted in urine. Niacin is one of the most stable of the B vitamins. It is resistant to heat and light, and to both acid and alkali environments. The human body is capable of converting the amino acid tryptophan to niacin when needed. However, when both tryptophan and niacin are deficient, tryptophan is used for protein synthesis.

 There are two coenzyme forms of niacin: nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotidephophate (NADP+). They both help break down and utilize proteins, fats, and carbohydrates for energy. Niacin is essential for growth and is involved in hormone synthesis.

Pellagra results from a combined deficiency of niacin and tryptophan. Long-term deficiency leads to central nervous system dysfunction manifested as confusion, apathy, disorientation, and eventually coma and death. Pellagra is rarely seen in industrialized countries, where it may be observed in people with rare disorder of tryptophan metabolism (Hartnup's disease), alcoholics, and those with diseases that affect food intake.

The liver can synthesize niacin from the essential aminoacid  tryptophan, but the synthesis is extremely slow; 60 mg of tryptophan are required to make one milligram of niacin. Dietary niacin deficiency tends to occur only in areas where people eat corn, the only grain low in niacin, as a staple food, and that don't use lime during maize (corn) meal/flour production. Alkali lime releases the tryptophan from the corn so that it can be absorbed in the gut, and converted to niacin.

 Niacin plays an important role in the production of several sex and stress-related hormones, particularly those made by the adrenal gland. Niacin, when taken in large doses, increases the level of high density lipoprotein (HDL) or "good" cholesterol in blood, and is sometimes prescribed for patients with low HDL, and at high risk of heart attack. Niacin (but not niacinamide) is also used in the treatment of hyperlipidemia because it reduces very low density lipoprotein (VLDL), a precursor of low density lipoprotein (LDL) or "bad" cholesterol, secretion from the liver, and inhibits cholesterol synthesis.

The main problem with the clinical use of niacin for dyslipidemia is the occurrence of skin flushing, even with moderate doses.

Recommended intake is expressed as milligrams of niacin equivalents (NE) to account for niacin synthesized from tryptophan. High doses taken orally as nicotinic acid at 1.5 to 2 grams per day can decrease cholesterol and triglyceride levels, and along with diet and exercise can slow or reverse the progression of heart disease. 

The nicotinamide form of niacin in multivitamin and B-complex tablets do not work for this purpose. Supplementation should be under a physician's guidance.

Food sources

Good sources of niacin include yeast, meat, poultry, red fishes (e.g., tuna, salmon), cereals (especially fortified cereals), legumes, and seeds. Milk, green leafy vegetables, coffee, and tea also provide some niacin. In plants, especially mature cereal grains like corn and wheat, niacin may be bound to sugar molecules in the form of glycosides, which significantly decrease niacin bioavailability.

 

Pantothenic Acid (Vitamin B3)

Pantothenic acid, also called vitamin B3, is a water-soluble vitamin required to sustain life. Pantothenic acid is needed to form coenzyme-A (CoA), and is critical in the metabolism and synthesis of carbohydrates, proteins, and fats. Its name is derived from the Greek pantothen meaning "from everywhere" and small quantities of pantothenic acid are found in nearly every food, with high amounts in whole grain cereals, legumes, eggs, meat, and royal jelly

Pantothenic acid is stable in moist heat. It is destroyed by vinegar (acid), baking soda (alkali), and dry heat. Significant losses occur during the processing and refining of foods. Pantothenic acid is released from coenzyme A in food in the small intestine. After absorption, it is transported to tissues, where coenzyme A is resynthesized. Coenzyme A is essential for the formation of energy as adenosine triphosphate (ATP) from carbohydrate, protein, alcohol, and fat.

 Coenzyme A is also important in the synthesis of fatty acids, cholesterol, steroids, and the neurotransmitter acetylcholine, which is essential for transmission of nerve impulses to muscles.

Dietary deficiency occurs in conjunction with other B-vitamin deficiencies. Pantothenic acid is used in the synthesis of coenzyme A (abbreviated as CoA). Coenzyme A may act as an acyl group carrier to form acetyl-CoA and other related compounds; this is a way to transport carbon atoms within the cell. The transfer of carbon atoms by coenzyme A is important in cellular respiration, as well as the biosynthesis of many important compounds such as fatty acids, cholesterol, and acetylcholine. Dietary deficiency occurs in conjunction with other B-vitamin deficiencies. In studies, experimentally induced deficiency in humans has resulted in headache, fatigue, impaired muscle coordination, abdominal cramps, and vomiting.

 In studies, experimentally induced deficiency in humans has resulted in headache, fatigue, impaired muscle coordination, abdominal cramps, and vomiting.

 

Biotin (Vitamin B8)

Biotin is a water soluble vitamin and a member of Vitamin B complex.  Also known as Vitamin H, Bios II, Co-enzyme R.  Its natural form is D-biotin.  It was isolated from liver in 1941 by Dr. Paul Gyorgy.

Biotin is the most stable of B vitamins. It is commonly found in two forms: the free vitamin and the protein-bound coenzyme form called biocytin. Biotin is absorbed in the small intestine, and it requires digestion by enzyme biotinidase, which is present in the small intestine. Biotin is synthesized by bacteria in the large intestine, but its absorption is questionable. Biotincontaining coenzymes participate in key reactions that produce energy from carbohydrate and synthesize fatty acids and protein.

Avidin is a protein in raw egg white, which can bind to the biotin in the stomach and decrease its absorption. Therefore, consumption of raw whites is of concern due to the risk of becoming biotin deficient. Cooking the egg white, however, destroysavidin. Deficiency may develop in infants born with a genetic defect that results in reduced levels of biotinidase. In the past, biotin deficiency was observed in infants fed biotin-deficient formula, so it is now added to infant formulas and other baby foods.

Vitamin B6

Pyridoxal, pyridoxamine and pyridoxine are collectively known as vitamin B6. All three compounds are efficiently converted to the biologically active form of vitamin B6, pyridoxal phosphate. This conversion is catalyzed by the ATP requiring enzyme,pyridoxal kinase.

Vitamin B6 is present in three forms: pyridoxal, pyridoxine, and pyridoxamine. All forms can be converted to the active vitamin-B6 coenzyme in the body. Pyridoxal phosphate (PLP) is the predominant biologically active form. Vitamin B6 is not stable in heat or in alkaline conditions, so cooking and food processing reduce its content in food. Both coenzyme and free forms are absorbed in the small intestine and transported to the liver, where they are phosphorylated and released into circulation, bound to albumin for transport to tissues. Vitamin B6 is stored in the muscle and only excreted in urine when intake is excessive.

Folic Acid, Folate, Folacin (Vitamin B9)

Folacin or folate, as it is usually called, is the form of vitamin B9 naturally present in foods, whereas folic acid is the synthetic form added to fortified foods and supplements. Both forms are absorbed in the small intestine and stored in the liver. The folic acid form, however, is more efficiently absorbed and available to the body. When consumed in excess of needs, both forms are excreted in urine and easily destroyed by heat, oxidation, and light.

Folic acid is a water soluble vitamin and is a member of the Vitamin B complex. Also known as Folacin, pteroyl-L-glutamic acid (PGA), vitamin Bc or vitamin M. Folic acid and its derivatives (mostly the tri and heptaglutamyl peptides) are widespread in nature. It is a specific growth factor for certain micro-organisms.  Found in yeast and liver in 1935.

All forms of this vitamin are readily converted to the coenzyme form called tetrahydrofolate (THFA), which plays a key role in transferring single-carbon methyl units during the synthesis of DNA and RNA, and in interconversions of amino acids. Folate also plays an important role in the synthesis of neurotransmitters. Meeting folate needs can improve mood and mental functions.

Long term high doses may cause Vitamin B12 losses from the body

Folate deficiency is one of the most common vitamin deficiencies. Early symptoms are nonspecific and include tiredness, irritability, and loss of appetite. Severe folate deficiency leads to macrocytic anemia, a condition in which cells in the bone marrow cannot divide normally and red blood cells remain in a large immature form called macrocytes. Large immature cells also appear along the length of the gastrointestinal tract, resulting in abdominal pain and diarrhea.

Pregnancy is a time of rapid cell multiplication and DNA synthesis, which increases the need for folate. Folate deficiency may lead to neural tube defects such as spina bifida (failure of the spine to close properly during the first month of pregnancy) and anencephaly (closure of the neural tube during fetal development, resulting in part of the cranium not being formed). Seventy percent of these defects could be avoided by adequate folate status before conception, and it is recommended that all women of childbearing age consume at least 400 micrograms (μg) of folic acid each day from fortified foods and supplements. Other groups at risk of deficiency include elderly persons and persons suffering from alcohol abuse or taking certain prescription drugs.

Vitamin B12

Vitamin B12 is found in its free-vitamin form, called cyanocobalamin, and in two active coenzyme forms. Absorption of vitamin B12 requires the presence of intrinsic factor,a protein synthesized by acid-producing cells of the stomach. The vitamin is absorbed in the terminal portion of the small intestine called the ileum. Most of body's supply of vitamin B12 is stored in the liver.

Vitamin B12

Vitamin B12 is defficiently conserved in the body, since most of it is secreted into bile and reabsorbed. This explains the slow development (about two years) of deficiency in people with reduced intake or absorption. Vitamin B12 is stable when heated and slowly loses its activity when exposed to light, oxygen, and acid or alkaline environments.

Vitamin B12 coenzymes help recycle folate coenzymes involved in the synthesis of DNA and RNA, and in the normal formation of red blood cells. Vitamin B12 prevents degeneration of the myelin sheaths that cover nerves and help maintain normal electrical conductivity through the nerves.

Active center of tetrahydrofolate (THF). Note that the N5 position is the site of attachment of methyl groups, the N10 the site for attachment of formyl and formimino groups and that both N5 and N10 bridge the methylene and methenyl groups

Vitamin-B12 deficiency results in pernicious anemia, which is caused by a genetic problem in the production of intrinsic factor. When this occurs, folate function is impaired, leading to macrocytic anemia due to interference in normal DNA synthesis. Unlikefolate deficiency, the anemia caused by vitamin-B12 deficiency is accompanied by symptoms of nerve degeneration, which if left untreated can result in paralysis and death.

Since vitamin B12 is well conserved in the body, it is difficult to become deficient from dietary factors alone, unless a person is a strict vegan and consumes a diet devoid of eggs and dairy for several years. Deficiency is usually observed when B12 absorption is hampered by disease or surgery to the stomach or ileum, damage to gastric mucosa by alcoholism, or prolonged use of anti-ulcer medications that affect secretion of intrinsic factor. Agerelated decrease in stomach-acid production also reduces absorption of B12 in elderly persons. These groups are advised to consume fortified foods or take a supplemental form of vitamin B12.

Vitamin C (Ascorbic Acid)

In 1746, James Lind, a British physician, conducted the first nutrition experiment on human beings in an effort to find a cure for scurvy.

Vitamin C is needed to form and maintain collagen, a fibrous protein that gives strength to connective tissues in skin, cartilage, bones, teeth, and joints. Collagen is also needed for the healing of wounds.

 When added to meals, vitamin C increases intestinal absorption of iron from plant-based foods. High concentration of vitamin C in white blood cells enables the immune system to function properly by providing protection against oxidative damage from free radicals generated during their action against bacterial, viral, or fungal infections.

Vitamin C also recycles oxidized vitamin E for reuse in cells, and it helps folic acid convert to its active form, (THF). Vitamin C helps synthesize carnitine, adrenaline, epinephrine, the neurotransmitter serotonin, the thyroid hormone thyroxine, bile acids, and steroid hormones.

A deficiency of vitamin C causes widespread connective tissue changes throughout the body. Deficiencies may occur in people who eat few fruits and vegetables, follow restrictive diets, or abuse alcohol and drugs. Smokers also have lower vitamin-C status. Supplementation may be prescribed by physicians to speed the healing of bedsores, skin ulcers, fractures, burns, and after surgery. Research has shown that doses up to 1 gram per day may have small effects on duration and severity of the common cold, but not on the prevention of its occurrence.

 Biological role of ascorbic acid:

acts as a cofactor in the en¬zymatic hydroxylation of proline to hydroxyproline and in other hydroxylation reactions;

inhibits the oxidation of hemoglobin;

accelerates the oxidation of glucose in pentose phosphate pathway;

reduces the disulfide bonds to sulfhydryl bonds;

is necessary for hydroxylation of cholesterol;

takes part in metabolism of adrenaline;

is necessary for the metabolism of mineral elements (Fe, Ca);

- accelerates the synthesis of glycogen in liver.

While at sea in May 1747, Lind provided some crewmembers with two oranges

 and one lemon per day, in addition to normal rations, while others continued on cider, vinegar or seawater, along with their normal rations. In the history of science this is considered to be the first example of a controlled experiment comparing results on two populations of a factor applied to one group only with all other factors the same.

 

 

In the hypovitaminosis of vitamin C the disease scurvy is developed. Main clinical symptoms of scurvy: delicacy, vertigo, palpitation, tachycardia, pain in the area of heart, dyspnea, petechias, odontorrhagia, dedentition.

Ascorbic acid and products of its decomposition are excreted from the organism via kidneys. In normal conditions 20-30 mg or 113,5-170,3 mkmol of ascorbic acid is excreted per day with urine.

In animal and plant tissues rather large concentrations of ascorbic acid are present, in comparison with other water-soluble vitamins; e.g., human blood plasma contains about 1 mg of ascorbic acid per 100 ml. Ascorbic acid is especially abundant in citrus fruits, tomatoes, currant, onion, garlic, cabbage, fruits of wild rose, needles of a pine-tree.

 Sources of vitamin C

Vitamin C is obtained through the diet by the vast majority of the world's population. The richest natural sources are fruits and vegetables, and of those, the camu camu fruit and the billygoat plum contain the highest concentration of the vitamin. It is alsopresent  in some cuts of meat, especially liver. Vitamin C as ascorbic acid is the most widely taken nutritional supplement and is available in a variety of forms from tablets and drink mixes to pure ascorbic acid crystals in capsules or as plain powder.

Vitamin P (bioflavonoids).

This is the group of compounds (rutin, hesperedin, katecholamines) supporting the elasticity of capillaries, strengthen their walls and decrease the permeability.

Vitamin P takes part in the oxidative-reduction processes. It oppresses the activity of enzyme hyaluronidase protecting thehyaluronic acid which is necessary for elasticity of vessel walls.

The deficiency of vitamin P in organism results in the petechias (dot hemorrhages on skin).

Day necessity of vitamin P is not clear exactly (about 25-50 mg).  In some diseases 1-2 g per day of vitamin P is administrated.

 

Investigation of fat soluble vitamins functional role in metabolism and cell functions realization.

 

Fat-soluble vitamins

Although fat-soluble vitamins have been studied intensively and widely used in human nutrition, we know less about their specific biological function than about the water-soluble vitamins.

Vitamin A.

Vitamin A occurs in two common forms, vitamin A1, or ret¬inol, the form most common in mammalian tissues and marine fishes, and vitamin, A2, common in freshwater fishes. Both are isoprenoid com¬pounds containing a six-membered carbocyclic ring and an eleven-carbon side chain.

Carotenoids are provitamins of vitamin A. Carotenoids widely distributed in plants, particularly a-, b-, and g-carotene. The carotenes have no vitamin A activity but are converted into vitamin A by enzymatic reactions in the intestinal mucosa and the liver. b-Carotene, a symmet¬rical molecule, is cleaved in its center to yield two molecules of retinol. Retinol occurs in the tissues of mammals and is transported in the blood.

In vitamin A deficiency young persons fail to grow, the bones and nervous system fail to develop properly, the skin becomes dry and thick¬ened, the kidneys and various glands degenerate, and both males and females become sterile.

Detailed information is available on the role of vitamin A in the visual_cycle in vertebrates. The human retina contains two types of light-sensitive photoreceptor cells. Rod-cells are adapted to sensing low light intensities, but not colors; they are the cells involved in night vision, whose function is im¬paired by vitamin A deficiency. Cone cells, which sense colors, are adapted for high light intensities.

Retinal rod cells contain many mem¬brane vesicles that serve as light receptors. About one-half of the protein in the membrane of these vesicles consists of the light-absorbing protein rhodopsin (visual purple). Rhodopsin consists of a protein, opsin, and tightly bound 11-cis-retinal, the aldehyde of vitamin A. When rhodopsin is exposed to light, the bound 11-cis-retinal undergoestrans¬formation into all-trans-retinal, which causes a substantial change in the configuration of the retinal molecule. This reaction isnonenzymatic. The isomerization of retinal is followed by a series of other molecular changes, ending in the dissociation of therhodopsin to yield free opsin and all-trans-retinal, which functions as a trigger setting off the nerve im-pulse.

 

In order for rhodopsin to be regenerated from opsin and all-trans-retinal, the latter must undergo isomerization back to 11-cis-retinal. This appears to occur in a sequence of en¬zymatic reactions catalyzed by two enzymes:

The 11-cis-retinal so formed now recombines with opsin to yield rhodopsin, thus completing the visual cycle.

Since vitamin A deficiency affects all tissues of mammals, not the retina alone, the role of retinal in the visual cycle does not represent the entire action of vitamin A. It appears possible that vitamin A may play a general role in:

The vitamin A requirement of man - 1,5-2 milligram per day.

Vitamin A is met in large part by green and yellow vegetables, such as lettuce, spinach, sweet potatoes, and carrots, which are rich in carotenes. Fish-liver oils are particularly rich in vitamin A. However, excessive intake of vitamin A is toxic and leads to easily fractured, fragile bones in children, as well as abnormal development of the fetus.

 

Vitamin D

Most important are vitamin D2, or ergocalciferol, and vitamin D3, or cholecalciferol, the form normally found in mammals. These compounds may be regarded as steroids.

It is now known that 7-dehydrocholesterol in the skin is the natural precursor of cholecalciferol in man; the conversion requires irradiation of the skin by sunlight. On a normal unsupplemented diet this is the major route by which people usually acquire vitamin D.

Rickets, a disease of growing bone, is developed in the deficiency of vitamin D in organism.

As with vitamin A, excessive intake of vitamin D causes the bones to become fragile and to undergo multiple fractures, suggesting that both vitamins play a role in biological transport and deposition of calcium.

 Most natural foods contain little of vitamin D; vitamin D in the diet comes largely from fish-liver oils, liver, yoke of eggs, butter. Vitamin D preparations available commercially are products of the ultraviolet irradiation of ergosterol from yeast.

Vitamin E

 Vitamin E was first recognized as a factor in vegetable oils that restores fertility in rats grown on cow's milk alone and otherwise incapable of bearing young. It was isolated from wheat germ and was given the name tocopherol. Several different tocopherolshaving vitamin E activity have been found in plants; the most active and abun¬dant is a-tocopherol.

 

Vitamin K  was first discovered as a nutritional factor required for normal blood-clotting time. At least two forms of vitamin K are known; vitamin K2 is believed to be the active form. Vitamin K deficiency cannot readily be produced in rats and other mammals because the vitamin is synthe-sized by intestinal bacteria.

The only known result of vitamin K deficiency is a failure in the biosynthesis of the enzyme proconvertin in the liver. This enzyme catalyzes a step in a complex sequence of reac¬tions involved in the formation of prothrombin, the pre¬cursor of thrombin, a protein that accelerates the conversion of fibrinogen into fibrin, the insoluble protein constituting the fibrous portion of blood clots.

 The compound dicumarol, an analog of vitamin K, produces symptoms in animals resembling vitamin K deficiency; it is believed to block the action of vitamin K. Dicumarol is used in clinical medicine to prevent clotting in blood vessels. Dicumarol is theantivitamin of vitamin K.

Some evidence indicates that vitamin K may function as a coenzyme in a specialized route of electron transport in animal tissues; since vitamin K is a quinone which can be reduced reversibly to a quinol, it may serve as an electron carrier.

Hypovitaminos of vitamin K in man can be developed in liver diseases when there is the decrease of bile acids amount in intestine and as result the inhibition of fat soluble substances absorption is observed.

Vitamin K is produced by many microorganisms in the intestine. also Plants (cabbage, tomato, lettuce)are natural sources of vitamin K.

Adult person requires 200-300 mkg of vitamin K per day.

Vitamins are nutrients required in tiny amounts for essential metabolic reactions in the body. The term vitamin does not include other essential nutrients such as dietary minerals, essential fatty acids, or essential amino acids, nor does it encompass the large number of other nutrients that promote health but that are not essential for life.

 Vitamins are bio-molecules that act both as catalysts and substrates in chemical reactions. When acting as a catalyst, vitamins are bound to enzymes and are called cofactors. (For example, vitamin K forms part of the proteases involved in blood clotting.) Vitamins also act as coenzymes to carry chemical groups between enzymes. (For example, folic acid carries various forms of carbon groups–methyl, formyl or methylene–in the cell.).

Vitamins have been produced as commodity chemicals and made widely available as inexpensive pills for several decades, allowing supplementation of the dietary intake.

Difference from water soluble vitamins: water soluble vitamins are included into coenzymes, don't have provitamins, are not included into the membranes, and hypervitaminoses are not peculiar for them.

 

Thiamin (Vitamin B1)

 Thiamin (also spelled thiamine) is a water-soluble B vitamin, previously known as vitamin B1 or aneurine. Isolated and characterized in the 1930s, thiamin was one of the first organic compounds to be recognized as a vitamin. Thiamin occurs in the human body as free thiamin and as various  phosphorylated forms: thiamin monophosphate (TMP), thiamin triphosphate (TTP), and thiamin pyrophosphate (TPP), which is also known as thiamin diphosphate.

Deficiency

Beriberi, the disease resulting from severe thiamin deficiency, was described in Chinese literature as early. Thiamin deficiency affects the cardiovascular, nervous, muscular, and  gastrointestinal systems. Beriberi has been termed dry, wet, or cerebral, depending on the systems affected by severe thiamin deficiency.

Food sources

 

A varied diet should provide most individuals with adequate thiamin to prevent deficiency. In the U.S. the average dietary thiamin intake for young adult men is about 2 mg/day and 1.2 mg/day for young adult women. A survey of people over the age of 60 found an average dietary thiamin intake of 1.4 mg/day for men and 1.1 mg/day for women. However, institutionalization and poverty both increase the likelihood of inadequate thiamin intake in the elderly.Whole grain cereals, legumes (e.g., beans and lentils)nuts, lean pork, and yeast are rich sources of thiamin. Because most of the thiamin is lost during the production of white flour and polished (milled) rice, white rice and foods made from white flour (e.g., bread and pasta) are fortified with thiamin in many Western countries. A number of thiamin-rich foods are listed in the table below along with their thiamin content in milligrams (mg). For more information on the nutrient content of foods, search the  USDA food composition database.

 

Riboflavin (Vitamin B2)

 Riboflavin is a water-soluble B vitamin, also known as vitamin B2. In the body, riboflavin is primarily found as an integral component of the coenzymes, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). Coenzymes derived from riboflavin are termed flavocoenzymes, and  enzymes that use a flavocoenzyme are called flavoproteins.

 Living organisms derive most of their energy from oxidation-reduction (redox) reactions, which are processes that involve the transfer of electrons. Flavocoenzymes participate in redox reactions in numerous metabolic pathways. Flavocoenzymes are critical for the  metabolism of carbohydrates, fats, and proteins. FAD is part of the  electron transport (respiratory) chain, which is central to energy production. In conjunction with  cytochrome P-450, flavocoenzymes also participate in the metabolism of drugs and toxins.

Glutathione reductase is a FAD-dependent enzyme that participates in the  redox cycle of glutathione. The glutathione redoxcycle plays a major role in protecting organisms from  reactive oxygen species, such as hydroperoxides. Glutathione reductaserequires FAD to regenerate two molecules of reduced glutathione from oxidized glutathione. Riboflavin deficiency has been associated with increased oxidative stress. Measurement of glutathione reductase activity in red blood cells is commonly used to assess riboflavin nutritional status.

Glutathione peroxidase, a selenium-containing enzyme, requires two molecules of reduced glutathione to break downhydroperoxides (see diagram).

Xanthine oxidase, another FAD-dependent enzyme,  catalyzes the oxidation of hypoxanthine and xanthine to uric acid. Uric acid is one of the most effective water-soluble  antioxidants in the blood. Riboflavin deficiency can result in decreased xanthine oxidaseactivity, reducing blood uric acid levels.

Deficiency

 

Ariboflavinosis is the medical name for clinical riboflavin deficiency. Riboflavin deficiency is rarely found in isolation; it occurs frequently in combination with deficiencies of other water-soluble vitamins. Symptoms of riboflavin deficiency include sore throat, redness and swelling of the lining of the mouth and throat, cracks or sores on the outsides of the lips (cheliosis) and at the corners of the mouth (angular stomatitis), inflammation and redness of the tongue (magenta tongue), and a moist, scaly skin inflammation (seborrheic dermatitis). Other symptoms may involve the formation of blood vessels in the clear covering of the eye (vascularizationof the cornea) and decreased red blood cell count in which the existing red blood cells contain normal levels of hemoglobin and are of normal size (normochromic normocytic anemia). Severe riboflavin deficiency may result in decreased conversion of vitamin B6 toits  coenzyme form (PLP) and decreased conversion of tryptophan to niacin (see Nutrient Interactions).

Food sources

 

Most plant and animal derived foods contain at least small quantities of riboflavin. In the U.S., wheat flour and bread have been enriched with riboflavin (as well as thiamin, niacin, and iron) since 1943. Data from large dietary surveys indicate that the average intake of riboflavin for men is about 2 mg/day and for women is about 1.5 mg/day; both intakes are well above the RDA. Intake levels were similar for a population of elderly men and women (1). Riboflavin is easily destroyed by exposure to light. For instance, up to 50% of the riboflavin in milk contained in a clear glass bottle can be destroyed after two hours of exposure to bright sunlight. Some foods with substantial amounts of riboflavin are listed in the table below along with their riboflavin content in milligrams (mg). For more information on the nutrient content of foods, search the  USDA food composition database.

Niacin (Vitamin B5)

   

Niacin exists in two forms, nicotinic acid and nicotinamide. Both forms are readily absorbed from the stomach and the small intestine. Niacin is stored in small amounts in the liver and transported to tissues, where it is converted to coenzyme forms. Any excess is excreted in urine. Niacin is one of the most stable of the B vitamins. It is resistant to heat and light, and to both acid and alkali environments. The human body is capable of converting the amino acid tryptophan to niacin when needed. However, when both tryptophan and niacin are deficient, tryptophan is used for protein synthesis.

 There are two coenzyme forms of niacin: nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotidephophate (NADP+). They both help break down and utilize proteins, fats, and carbohydrates for energy. Niacin is essential for growth and is involved in hormone synthesis.

Pellagra results from a combined deficiency of niacin and tryptophan. Long-term deficiency leads to central nervous system dysfunction manifested as confusion, apathy, disorientation, and eventually coma and death. Pellagra is rarely seen in industrialized countries, where it may be observed in people with rare disorder of tryptophan metabolism (Hartnup's disease), alcoholics, and those with diseases that affect food intake.

The liver can synthesize niacin from the essential aminoacid  tryptophan, but the synthesis is extremely slow; 60 mg of tryptophan are required to make one milligram of niacin. Dietary niacin deficiency tends to occur only in areas where people eat corn, the only grain low in niacin, as a staple food, and that don't use lime during maize (corn) meal/flour production. Alkali lime releases the tryptophan from the corn so that it can be absorbed in the gut, and converted to niacin.

 Niacin plays an important role in the production of several sex and stress-related hormones, particularly those made by the adrenal gland. Niacin, when taken in large doses, increases the level of high density lipoprotein (HDL) or "good" cholesterol in blood, and is sometimes prescribed for patients with low HDL, and at high risk of heart attack. Niacin (but not niacinamide) is also used in the treatment of hyperlipidemia because it reduces very low density lipoprotein (VLDL), a precursor of low density lipoprotein (LDL) or "bad" cholesterol, secretion from the liver, and inhibits cholesterol synthesis.

The main problem with the clinical use of niacin for dyslipidemia is the occurrence of skin flushing, even with moderate doses.

Recommended intake is expressed as milligrams of niacin equivalents (NE) to account for niacin synthesized from tryptophan. High doses taken orally as nicotinic acid at 1.5 to 2 grams per day can decrease cholesterol and triglyceride levels, and along with diet and exercise can slow or reverse the progression of heart disease. 

The nicotinamide form of niacin in multivitamin and B-complex tablets do not work for this purpose. Supplementation should be under a physician's guidance.

Food sources

Good sources of niacin include yeast, meat, poultry, red fishes (e.g., tuna, salmon), cereals (especially fortified cereals), legumes, and seeds. Milk, green leafy vegetables, coffee, and tea also provide some niacin. In plants, especially mature cereal grains like corn and wheat, niacin may be bound to sugar molecules in the form of glycosides, which significantly decrease niacin bioavailability.

 

Pantothenic Acid (Vitamin B3)

Pantothenic acid, also called vitamin B3, is a water-soluble vitamin required to sustain life. Pantothenic acid is needed to form coenzyme-A (CoA), and is critical in the metabolism and synthesis of carbohydrates, proteins, and fats. Its name is derived from the Greek pantothen meaning "from everywhere" and small quantities of pantothenic acid are found in nearly every food, with high amounts in whole grain cereals, legumes, eggs, meat, and royal jelly

Pantothenic acid is stable in moist heat. It is destroyed by vinegar (acid), baking soda (alkali), and dry heat. Significant losses occur during the processing and refining of foods. Pantothenic acid is released from coenzyme A in food in the small intestine. After absorption, it is transported to tissues, where coenzyme A is resynthesized. Coenzyme A is essential for the formation of energy as adenosine triphosphate (ATP) from carbohydrate, protein, alcohol, and fat.

 Coenzyme A is also important in the synthesis of fatty acids, cholesterol, steroids, and the neurotransmitter acetylcholine, which is essential for transmission of nerve impulses to muscles.

Dietary deficiency occurs in conjunction with other B-vitamin deficiencies. Pantothenic acid is used in the synthesis of coenzyme A (abbreviated as CoA). Coenzyme A may act as an acyl group carrier to form acetyl-CoA and other related compounds; this is a way to transport carbon atoms within the cell. The transfer of carbon atoms by coenzyme A is important in cellular respiration, as well as the biosynthesis of many important compounds such as fatty acids, cholesterol, and acetylcholine. Dietary deficiency occurs in conjunction with other B-vitamin deficiencies. In studies, experimentally induced deficiency in humans has resulted in headache, fatigue, impaired muscle coordination, abdominal cramps, and vomiting.

 In studies, experimentally induced deficiency in humans has resulted in headache, fatigue, impaired muscle coordination, abdominal cramps, and vomiting.

 

Biotin (Vitamin B8)

Biotin is a water soluble vitamin and a member of Vitamin B complex.  Also known as Vitamin H, Bios II, Co-enzyme R.  Its natural form is D-biotin.  It was isolated from liver in 1941 by Dr. Paul Gyorgy.

Biotin is the most stable of B vitamins. It is commonly found in two forms: the free vitamin and the protein-bound coenzyme form called biocytin. Biotin is absorbed in the small intestine, and it requires digestion by enzyme biotinidase, which is present in the small intestine. Biotin is synthesized by bacteria in the large intestine, but its absorption is questionable. Biotincontaining coenzymes participate in key reactions that produce energy from carbohydrate and synthesize fatty acids and protein.

Avidin is a protein in raw egg white, which can bind to the biotin in the stomach and decrease its absorption. Therefore, consumption of raw whites is of concern due to the risk of becoming biotin deficient. Cooking the egg white, however, destroysavidin. Deficiency may develop in infants born with a genetic defect that results in reduced levels of biotinidase. In the past, biotin deficiency was observed in infants fed biotin-deficient formula, so it is now added to infant formulas and other baby foods.

Vitamin B6

Pyridoxal, pyridoxamine and pyridoxine are collectively known as vitamin B6. All three compounds are efficiently converted to the biologically active form of vitamin B6, pyridoxal phosphate. This conversion is catalyzed by the ATP requiring enzyme,pyridoxal kinase.

Vitamin B6 is present in three forms: pyridoxal, pyridoxine, and pyridoxamine. All forms can be converted to the active vitamin-B6 coenzyme in the body. Pyridoxal phosphate (PLP) is the predominant biologically active form. Vitamin B6 is not stable in heat or in alkaline conditions, so cooking and food processing reduce its content in food. Both coenzyme and free forms are absorbed in the small intestine and transported to the liver, where they are phosphorylated and released into circulation, bound to albumin for transport to tissues. Vitamin B6 is stored in the muscle and only excreted in urine when intake is excessive.

Folic Acid, Folate, Folacin (Vitamin B9)

Folacin or folate, as it is usually called, is the form of vitamin B9 naturally present in foods, whereas folic acid is the synthetic form added to fortified foods and supplements. Both forms are absorbed in the small intestine and stored in the liver. The folic acid form, however, is more efficiently absorbed and available to the body. When consumed in excess of needs, both forms are excreted in urine and easily destroyed by heat, oxidation, and light.

Folic acid is a water soluble vitamin and is a member of the Vitamin B complex. Also known as Folacin, pteroyl-L-glutamic acid (PGA), vitamin Bc or vitamin M. Folic acid and its derivatives (mostly the tri and heptaglutamyl peptides) are widespread in nature. It is a specific growth factor for certain micro-organisms.  Found in yeast and liver in 1935.

All forms of this vitamin are readily converted to the coenzyme form called tetrahydrofolate (THFA), which plays a key role in transferring single-carbon methyl units during the synthesis of DNA and RNA, and in interconversions of amino acids. Folate also plays an important role in the synthesis of neurotransmitters. Meeting folate needs can improve mood and mental functions.

Long term high doses may cause Vitamin B12 losses from the body

Folate deficiency is one of the most common vitamin deficiencies. Early symptoms are nonspecific and include tiredness, irritability, and loss of appetite. Severe folate deficiency leads to macrocytic anemia, a condition in which cells in the bone marrow cannot divide normally and red blood cells remain in a large immature form called macrocytes. Large immature cells also appear along the length of the gastrointestinal tract, resulting in abdominal pain and diarrhea.

Pregnancy is a time of rapid cell multiplication and DNA synthesis, which increases the need for folate. Folate deficiency may lead to neural tube defects such as spina bifida (failure of the spine to close properly during the first month of pregnancy) and anencephaly (closure of the neural tube during fetal development, resulting in part of the cranium not being formed). Seventy percent of these defects could be avoided by adequate folate status before conception, and it is recommended that all women of childbearing age consume at least 400 micrograms (μg) of folic acid each day from fortified foods and supplements. Other groups at risk of deficiency include elderly persons and persons suffering from alcohol abuse or taking certain prescription drugs.

Vitamin B12

Vitamin B12 is found in its free-vitamin form, called cyanocobalamin, and in two active coenzyme forms. Absorption of vitamin B12 requires the presence of intrinsic factor,a protein synthesized by acid-producing cells of the stomach. The vitamin is absorbed in the terminal portion of the small intestine called the ileum. Most of body's supply of vitamin B12 is stored in the liver.

Vitamin B12

Vitamin B12 is defficiently conserved in the body, since most of it is secreted into bile and reabsorbed. This explains the slow development (about two years) of deficiency in people with reduced intake or absorption. Vitamin B12 is stable when heated and slowly loses its activity when exposed to light, oxygen, and acid or alkaline environments.

Vitamin B12 coenzymes help recycle folate coenzymes involved in the synthesis of DNA and RNA, and in the normal formation of red blood cells. Vitamin B12 prevents degeneration of the myelin sheaths that cover nerves and help maintain normal electrical conductivity through the nerves.

Active center of tetrahydrofolate (THF). Note that the N5 position is the site of attachment of methyl groups, the N10 the site for attachment of formyl and formimino groups and that both N5 and N10 bridge the methylene and methenyl groups

Vitamin-B12 deficiency results in pernicious anemia, which is caused by a genetic problem in the production of intrinsic factor. When this occurs, folate function is impaired, leading to macrocytic anemia due to interference in normal DNA synthesis. Unlikefolate deficiency, the anemia caused by vitamin-B12 deficiency is accompanied by symptoms of nerve degeneration, which if left untreated can result in paralysis and death.

Since vitamin B12 is well conserved in the body, it is difficult to become deficient from dietary factors alone, unless a person is a strict vegan and consumes a diet devoid of eggs and dairy for several years. Deficiency is usually observed when B12 absorption is hampered by disease or surgery to the stomach or ileum, damage to gastric mucosa by alcoholism, or prolonged use of anti-ulcer medications that affect secretion of intrinsic factor. Agerelated decrease in stomach-acid production also reduces absorption of B12 in elderly persons. These groups are advised to consume fortified foods or take a supplemental form of vitamin B12.

Vitamin C (Ascorbic Acid)

In 1746, James Lind, a British physician, conducted the first nutrition experiment on human beings in an effort to find a cure for scurvy.

Vitamin C is needed to form and maintain collagen, a fibrous protein that gives strength to connective tissues in skin, cartilage, bones, teeth, and joints. Collagen is also needed for the healing of wounds.

 When added to meals, vitamin C increases intestinal absorption of iron from plant-based foods. High concentration of vitamin C in white blood cells enables the immune system to function properly by providing protection against oxidative damage from free radicals generated during their action against bacterial, viral, or fungal infections.

Vitamin C also recycles oxidized vitamin E for reuse in cells, and it helps folic acid convert to its active form, (THF). Vitamin C helps synthesize carnitine, adrenaline, epinephrine, the neurotransmitter serotonin, the thyroid hormone thyroxine, bile acids, and steroid hormones.

A deficiency of vitamin C causes widespread connective tissue changes throughout the body. Deficiencies may occur in people who eat few fruits and vegetables, follow restrictive diets, or abuse alcohol and drugs. Smokers also have lower vitamin-C status. Supplementation may be prescribed by physicians to speed the healing of bedsores, skin ulcers, fractures, burns, and after surgery. Research has shown that doses up to 1 gram per day may have small effects on duration and severity of the common cold, but not on the prevention of its occurrence.

 Biological role of ascorbic acid:

acts as a cofactor in the en¬zymatic hydroxylation of proline to hydroxyproline and in other hydroxylation reactions;

inhibits the oxidation of hemoglobin;

accelerates the oxidation of glucose in pentose phosphate pathway;

reduces the disulfide bonds to sulfhydryl bonds;

is necessary for hydroxylation of cholesterol;

takes part in metabolism of adrenaline;

is necessary for the metabolism of mineral elements (Fe, Ca);

- accelerates the synthesis of glycogen in liver.

While at sea in May 1747, Lind provided some crewmembers with two oranges

 and one lemon per day, in addition to normal rations, while others continued on cider, vinegar or seawater, along with their normal rations. In the history of science this is considered to be the first example of a controlled experiment comparing results on two populations of a factor applied to one group only with all other factors the same.

 

 

In the hypovitaminosis of vitamin C the disease scurvy is developed. Main clinical symptoms of scurvy: delicacy, vertigo, palpitation, tachycardia, pain in the area of heart, dyspnea, petechias, odontorrhagia, dedentition.

Ascorbic acid and products of its decomposition are excreted from the organism via kidneys. In normal conditions 20-30 mg or 113,5-170,3 mkmol of ascorbic acid is excreted per day with urine.

In animal and plant tissues rather large concentrations of ascorbic acid are present, in comparison with other water-soluble vitamins; e.g., human blood plasma contains about 1 mg of ascorbic acid per 100 ml. Ascorbic acid is especially abundant in citrus fruits, tomatoes, currant, onion, garlic, cabbage, fruits of wild rose, needles of a pine-tree.

 Sources of vitamin C

Vitamin C is obtained through the diet by the vast majority of the world's population. The richest natural sources are fruits and vegetables, and of those, the camu camu fruit and the billygoat plum contain the highest concentration of the vitamin. It is alsopresent  in some cuts of meat, especially liver. Vitamin C as ascorbic acid is the most widely taken nutritional supplement and is available in a variety of forms from tablets and drink mixes to pure ascorbic acid crystals in capsules or as plain powder.

Vitamin P (bioflavonoids).

This is the group of compounds (rutin, hesperedin, katecholamines) supporting the elasticity of capillaries, strengthen their walls and decrease the permeability.

Vitamin P takes part in the oxidative-reduction processes. It oppresses the activity of enzyme hyaluronidase protecting thehyaluronic acid which is necessary for elasticity of vessel walls.

The deficiency of vitamin P in organism results in the petechias (dot hemorrhages on skin).

Day necessity of vitamin P is not clear exactly (about 25-50 mg).  In some diseases 1-2 g per day of vitamin P is administrated.

 

Investigation of fat soluble vitamins functional role in metabolism and cell functions realization.

 

Fat-soluble vitamins

Although fat-soluble vitamins have been studied intensively and widely used in human nutrition, we know less about their specific biological function than about the water-soluble vitamins.

Vitamin A.

Vitamin A occurs in two common forms, vitamin A1, or ret¬inol, the form most common in mammalian tissues and marine fishes, and vitamin, A2, common in freshwater fishes. Both are isoprenoid com¬pounds containing a six-membered carbocyclic ring and an eleven-carbon side chain.

Carotenoids are provitamins of vitamin A. Carotenoids widely distributed in plants, particularly a-, b-, and g-carotene. The carotenes have no vitamin A activity but are converted into vitamin A by enzymatic reactions in the intestinal mucosa and the liver. b-Carotene, a symmet¬rical molecule, is cleaved in its center to yield two molecules of retinol. Retinol occurs in the tissues of mammals and is transported in the blood.

In vitamin A deficiency young persons fail to grow, the bones and nervous system fail to develop properly, the skin becomes dry and thick¬ened, the kidneys and various glands degenerate, and both males and females become sterile.

Detailed information is available on the role of vitamin A in the visual_cycle in vertebrates. The human retina contains two types of light-sensitive photoreceptor cells. Rod-cells are adapted to sensing low light intensities, but not colors; they are the cells involved in night vision, whose function is im¬paired by vitamin A deficiency. Cone cells, which sense colors, are adapted for high light intensities.

Retinal rod cells contain many mem¬brane vesicles that serve as light receptors. About one-half of the protein in the membrane of these vesicles consists of the light-absorbing protein rhodopsin (visual purple). Rhodopsin consists of a protein, opsin, and tightly bound 11-cis-retinal, the aldehyde of vitamin A. When rhodopsin is exposed to light, the bound 11-cis-retinal undergoestrans¬formation into all-trans-retinal, which causes a substantial change in the configuration of the retinal molecule. This reaction isnonenzymatic. The isomerization of retinal is followed by a series of other molecular changes, ending in the dissociation of therhodopsin to yield free opsin and all-trans-retinal, which functions as a trigger setting off the nerve im-pulse.

 

In order for rhodopsin to be regenerated from opsin and all-trans-retinal, the latter must undergo isomerization back to 11-cis-retinal. This appears to occur in a sequence of en¬zymatic reactions catalyzed by two enzymes:

The 11-cis-retinal so formed now recombines with opsin to yield rhodopsin, thus completing the visual cycle.

Since vitamin A deficiency affects all tissues of mammals, not the retina alone, the role of retinal in the visual cycle does not represent the entire action of vitamin A. It appears possible that vitamin A may play a general role in:

The vitamin A requirement of man - 1,5-2 milligram per day.

Vitamin A is met in large part by green and yellow vegetables, such as lettuce, spinach, sweet potatoes, and carrots, which are rich in carotenes. Fish-liver oils are particularly rich in vitamin A. However, excessive intake of vitamin A is toxic and leads to easily fractured, fragile bones in children, as well as abnormal development of the fetus.

 

Vitamin D

Most important are vitamin D2, or ergocalciferol, and vitamin D3, or cholecalciferol, the form normally found in mammals. These compounds may be regarded as steroids.

It is now known that 7-dehydrocholesterol in the skin is the natural precursor of cholecalciferol in man; the conversion requires irradiation of the skin by sunlight. On a normal unsupplemented diet this is the major route by which people usually acquire vitamin D.

Rickets, a disease of growing bone, is developed in the deficiency of vitamin D in organism.

As with vitamin A, excessive intake of vitamin D causes the bones to become fragile and to undergo multiple fractures, suggesting that both vitamins play a role in biological transport and deposition of calcium.

 Most natural foods contain little of vitamin D; vitamin D in the diet comes largely from fish-liver oils, liver, yoke of eggs, butter. Vitamin D preparations available commercially are products of the ultraviolet irradiation of ergosterol from yeast.

Vitamin E

 Vitamin E was first recognized as a factor in vegetable oils that restores fertility in rats grown on cow's milk alone and otherwise incapable of bearing young. It was isolated from wheat germ and was given the name tocopherol. Several different tocopherolshaving vitamin E activity have been found in plants; the most active and abun¬dant is a-tocopherol.

 

Vitamin K  was first discovered as a nutritional factor required for normal blood-clotting time. At least two forms of vitamin K are known; vitamin K2 is believed to be the active form. Vitamin K deficiency cannot readily be produced in rats and other mammals because the vitamin is synthe-sized by intestinal bacteria.

The only known result of vitamin K deficiency is a failure in the biosynthesis of the enzyme proconvertin in the liver. This enzyme catalyzes a step in a complex sequence of reac¬tions involved in the formation of prothrombin, the pre¬cursor of thrombin, a protein that accelerates the conversion of fibrinogen into fibrin, the insoluble protein constituting the fibrous portion of blood clots.

 The compound dicumarol, an analog of vitamin K, produces symptoms in animals resembling vitamin K deficiency; it is believed to block the action of vitamin K. Dicumarol is used in clinical medicine to prevent clotting in blood vessels. Dicumarol is theantivitamin of vitamin K.

Some evidence indicates that vitamin K may function as a coenzyme in a specialized route of electron transport in animal tissues; since vitamin K is a quinone which can be reduced reversibly to a quinol, it may serve as an electron carrier.

Hypovitaminos of vitamin K in man can be developed in liver diseases when there is the decrease of bile acids amount in intestine and as result the inhibition of fat soluble substances absorption is observed.

Vitamin K is produced by many microorganisms in the intestine. also Plants (cabbage, tomato, lettuce)are natural sources of vitamin K.

Adult person requires 200-300 mkg of vitamin K per day.