Vitamins

Information Resources

Information Resources

1. Biological Chemistry: Textbook / A.L. Zagayko, L.M. Voronina, G.B. Kravchenko, K.V. Strel`chenko. – Kharkiv: NUPh; Original, 2011. – 195-211 p.

2. Training Journal for Licensed Exam “KROK-1”: Study Material in Biological Chemistry. – Kharkiv: NUPh, 2017. – 117-142 p.

3. Laboratory Manual on Biochemistry. Kharkiv: NUPh, 2017. - 65-68 p.

4. Vitamins: Water and Fat Soluble: The Medical Biochemistry Page. Available on: https://themedicalbiochemistrypage.org/vitamins.php.

5. Minerals: Critical Micronutrients: The Medical Biochemistry Page. Available on: https://themedicalbiochemistrypage.org/minerals.php.

VITAMINS

Vitamins are organic compounds required in diet in small amounts and are essential to perform specific biologic functions for normal metabolism. The lack of vitamins in the diet or other reasons causes deficiency diseases. Human body either does not produce enough of them, or non at all.

VITAMINS

The word "Vitamin" causes from the Greek word, which means "vital for life".

Vitamin Classification

Coenzyme Vitamins Hormone-like vitamins Redox vitamins

(coenzymes and (regulation) (antioxidants)

their precursors), vitamins A and D vitamins А, Е, С, and Р

ex. – vitamins group В

- Nutritional factors (come from food or synthesized by the intestinal microflora);

- Necessary in relatively small quantities;

- In the absence of a developing characteristic syndrome - hypo-or avitaminosis;

- Not used as plastic or energy material

General Information

Hypovitaminosis – is a lack of some vitamins.

Hypervitaminosis – is a excess of some vitamins.

Avitaminosis – is an absence of some vitamins.

Provitamins – are precursors of vitamins.

Antivitamins – is chemical compounds which restrict activity of some vitamins.

A Brief History of Vitamins

Compatibility of vitamins

Compatible vitamins and minerals

А, С and Е.

В2, В9, В6 and К.

В12, В9 and В5.

В3 with ferum.

Д, К, В12, В6 and calcium.

Е and sulfur.

Do not combine vitamins and minerals (between taking one and the other should pass from 4 to 6 hours):

В12 and К with vitamin А.

Е and iron, vitamin К.

There are a lot of agonists of В12: В1, В3, С and Е,moreover copper, manganese and iron.

Zinc and Vitamin B9.

Vitamin E and iron.

Copper and Vitamin C.

Vitamin B5 and copper.

It is categorically not possible to take calcium with iron, zinc and manganese.

Copper and manganese.

Zinc with chlorine and copper.

Iron does not interfere with manganese, zinc, chlorine, magnesium.

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Vitamin A

Retinoic acid

Retinol

Gene Control Exerted by Retinol and Retinoic Acid

Vitamin A can get in cell membranes due to it fat-soluble and penetrate into nuclear. Within nuclear both retinol and retinoic acid bind to specific receptor proteins. Following binding, the receptor-vitamin complex interacts with specific sequences in several genes involved in growth and differentiation and affects expression of these genes. Several genes whose patterns of expression are altered by retinoic acid are involved in the earliest processes of embryogenesis.

Vitamin A consists of three biologically active molecules, retinol, retinal (retinaldehyde) and retinoic acid.

Vitamin A

Retinal

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Additional Role of Retinol

Retinol also functions in the synthesis of certain glycoproteins and mucopolysaccharides necessary for mucous production and normal growth regulation. It’s known that retinol and carotine posses of antihystamine properties.

Vision and the Role of Vitamin A

Photoreception in the eye is the function of two specialized cell types located in the retina; the rod and cone cells. Both rod and cone cells contain a photoreceptor pigment in their membranes. The photosensitive compound of most mammalian eyes is a protein called opsin to which is covalently coupled an aldehyde of vitamin A.

When the it’s light, rhodopsin is exposed and when it’s dark rhodopsin is synthesized. That’s why we can see in the darkness only when we have enough retinal.

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Vitamin D

The active form of vitamin D, 1,25(OH)2D, inhibits proliferation and stimulates the differentiation of cells. Calcitriol functions to regulate serum calcium and phosphorous levels.

Vitamin D

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Vitamin D is a fat-soluble vitamin that is essential for maintaining normal calcium metabolism. Vitamin D3 (cholecalciferol) can be synthesized by humans in the skin from 7-dehydrocholesterol upon exposure to ultraviolet-B (UVB) radiation from sunlight, or it can be obtained from the diet. Plants synthesize vitamin D2 (ergocalciferol). The biologically active form of the vitamin is 1,25-dihydroxy vitamin D3 (1,25-(OH)2D3, also termed calcitriol.

Vitamin E

a-Tocopherol

The term vitamin E describes a family of antioxidants, alpha-, beta-, gamma- and delta- tocopherols.

The main function of a-tocopherol in humans appears to be that of an antioxidant. a-Tocopherol, is uniquely suited to intercepting free radicals and preventing a chain reaction of lipid destruction. Aside from maintaining the integrity of cell membranes, a-tocopherol also protects the fats in low density lipoproteins from oxidation.

When a molecule of a-tocopherol neutralizes a free radical, it is altered in such a way that its antioxidant capacity is lost. However, other antioxidants, such as vitamin C, are capable of regenerating the antioxidant capacity of a-tocopherol.

Vitamin E

Deficiency of vitamin E is very rare in humans, but when laboratory animals are fed diets depleted of vitamin E, they develop scaly skin, muscular weakness and sterility.

Additional Role of Vitamin E

a-Tocopherol is known are an important cell signaling molecule, as well as to affect the expression and activity of immune and inflammatory cells.

Vitamin K

Vitamin K1

Vitamin K is essential for the functioning of several proteins involved in blood clotting. The known biological role is that of the required coenzyme for synthesis of key factors of blood coagulation in the liver.

There are two naturally occurring forms of vitamin K.

Plants synthesize phylloquinone, also known as vitamin K1. Vitamin K2 can be synthesized by bacteria in the intestina.

Vitamin K2

Vitamin K

That’s why we have deficiency of this vitamin if microphlora in our intestine have been killed by antibiotics or sulfanilamide medicine.

Vitamin K deficiency results in impaired blood clotting. Symptoms include easy bruising and bleeding. Adults at risk of vitamin K deficiency include those taking vitamin K antagonist anticoagulant drugs and individuals with significant liver damage or disease. Newborn babies that are exclusively breast-fed are at increased risk of vitamin K deficiency for the following reasons: 1) human milk is relatively low in vitamin K compared to formula, 2) the newborn's intestines are not yet colonized with bacteria that synthesize menaquinones. Vitamin K deficiency in newborns may result in a bleeding disorder called vitamin K deficiency bleeding of the newborn (hemorrhagic syndrome ).

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Some oral anticoagulants, such as warfarin, aspirin, gerudin (substation which can be synthesized in leech) inhibit coagulation through antagonism of the action of vitamin K.

Ascorbic acid (vitamin C)

Vitamin C is responsible for over 300 functions in the body, ranging from being the top anti-oxidant, producing collagen, keeping the immune system healthy, lowering blood pressure and relieving stress. The main function of ascorbate is as a reducing agent in a number of different reactions. The most important reaction requiring ascorbate as a cofactor is the hydroxylation of proline residues in collagen. Vitamin C is, therefore, required for the maintenance of normal connective tissue as well as for wound healing since synthesis of connective tissue is the first event in wound tissue remodeling.

Several other metabolic reactions require vitamin C as a cofactor. These include the cataboism of tyrosine and the synthesis of epinephrine from tyrosine and the synthesis of the bile acids.

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Thereby, vitamin C acts as an electron donor for eight different enzymes:

Three enzymes participate in collagen hydroxylation. These reactions add hydroxyl groups to the amino acids proline or lysine in the collagen molecule via prolyl hydroxylase and lysyl hydroxylase, both requiring vitamin C as a cofactor. Hydroxylation allows the collagen molecule to assume its triple helix structure, and thus vitamin C is essential to the development and maintenance of scar tissue, blood vessels, and cartilage.

Two enzymes are necessary for synthesis of carnitine. Carnitine is essential for the transport of fatty acids into mitochondria for ATP generation.

The remaining three enzymes have the following functions in common, but have other functions as well:

dopamine beta hydroxylase participates in the biosynthesis of norepinephrine from dopamine.

another enzyme adds amide groups to peptide hormones, greatly increasing their stability.

one modulates tyrosine metabolism.

Deficiency

Connective tissue destruction under scurvy

Food sources

Deficiency in vitamin C leads to the disease scurvy due to the role of the vitamin in the post-translational modification of collagens. Scurvy is characterized by easily bruised skin, muscle fatigue, soft swollen gums, decreased wound healing and hemorrhaging, osteoporosis, anemia, and loose teeth.

Sources of Vitamin P:

Fruits and vegetables a part of their diets will automatically get sufficient quantities of Vitamin P. Specifically, the brightly colored fruits and vegetables in shades of red, orange and yellow are the best sources.

Mangoes, apricots, oranges, grapefruit and other citrus fruits, lemons, cherries, blackcurrants, plums, and grapes are good fruit sources.

Carrots, tomatoes, green peppers, broccoli and onions are good vegetable sources.

Red wine also is a good source of Bioflavonoids.

Vitamin P

Vitamin P are a group of water soluble substances which comprise a number of factors including herpseridin, myrecetin, nobiletin, rutin, tangeritin and quercetin and there is no known toxicity symptoms reported with bioflavanoids. This helps keep capillaries strong and a stronger blood vessel system is better able to protect itself from disease and infection.

In the case of Vitamin P, its main function is to keep blood vessels healthy. Bioflavoids have antioxidant capabilities. Antioxidants prevent many serious diseases from developing by neutralizing free radicals.

Another important quality of Bioflavonoids is their effectiveness as an anti-inflammatory. It's possible that consuming Bioflavonoids benefits muscle and joints by helping bruises in these areas heal faster.

B VITAMINS

B vitamins are precursors to coenzymes.

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Thiamin (B1)

Function

TPP is necessary as a cofactor for the enzyme decarboxylase which catalyzed reactions of decarboxylation of a-ketoacids, for example pyruvat and alpha-ketoglytarate. TPP is a cofactor for transketolase catalyzed reactions of the pentose phosphate pathway. A deficiency in thiamin intake leads to a severely reduced capacity of cells to generate energy as a result of its role in these reactions.

Deficiency

The earliest symptoms of thiamin deficiency include appetite suppression, nausea as well as mental depression, peripheral neuropathy and fatigue. Chronic thiamin deficiency leads to more severe neurological symptoms including ataxia, mental confusion and loss of eye coordination. Other clinical symptoms of prolonged thiamin deficiency are related to cardiovascular and musculature defects.

Thiamin

Thiamin is rapidly converted to its active form, thiamin pyrophosphate, TPP.

TPP

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The dietary requirement for thiamin is proportional to the caloric intake of the diet and ranges from 1,0 – 1,5 mg/day for normal adults.

The severe thiamin deficiency disease known as Beriberi, is the result of a diet that is carbohydrate rich and thiamin deficient (polyneuritis).

Riboflavin (B2)

The enzymes that require FMN or FAD as cofactors are flavin-depended dehydrogenase (the second enzyme of electron transport chain). Vitamin B2 is also known as cofactor of amino acids oxidase which provide the process of transamination.

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Riboflavin is the precursor for the coenzymes, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD).

Riboflavin deficiencies are rare in d civilized country due to the presence of adequate amounts of the vitamin in eggs, milk, meat and cereals. Riboflavin deficiency is often seen in chronic alcoholics due to their poor dietetic habits.

Symptoms associated with riboflavin deficiency include, glossitis, seborrhea, angular stomatitis.

FAD

The normal daily requirement for riboflavin is 1.2 - 1.7 mg/day for normal adults.

Food Sourses

Riboflavin

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Niacin (B3, nicotinic acid and nicotinamide)

Niacin is required for the synthesis of the active forms of vitamin B3, nicotinamide adenine dinucleotide (NAD+) and nicotinamide adenine dinucleotide phosphate (NADP+). Both NAD+ and NADP+ function as cofactors for numerous dehydrogenase, e.g., lactate and malate dehydrogenases.

The recommended daily requirement for niacin is 13-19 niacin equivalents (NE) per day for a normal adult. One NE is equivalent to 1 mg of free niacin).

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Nicotinic acid can reduce plasma cholesterol levels and has been shown to be a useful therapeutic for hypercholesterolemia. The major action of nicotinic acid in this capacity is a reduction in fatty acid mobilization from adipose tissue. But nicotinic acid can be synthesized in our cells from amino acid tryptophane in the presence in the presence of vitamin B6.

Deficiency

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A diet deficient in niacin leads to glossitis of the tongue, dermatitis, weight loss, diarrhea, depression and dementia. The severe symptoms, depression, dermatitis and diarrhea, are associated with the condition known as pellagra.

Pantothenic acid (B5)

Coenzyme A reacts with acyl groups, giving rise to thioester derivatives, such as acetyl-CoA, succinyl-CoA, malonyl-CoA, and 3-hydroxy-3-methylglutaryl (HMG)-CoA. Coenzyme A and its acyl derivatives are required for reactions that generate energy from the degradation of dietary fat, carbohydrates, and proteins. In addition, coenzyme A in the form of acetyl-CoA and succinyl-CoA is involved in the citric acid cycle, in the synthesis of essential fats, cholesterol, steroid hormones, vitamins A and D, the neurotransmitter acetylcholine, and in the fatty acid β-oxidation pathway. Coenzyme A derivatives are also required for the synthesis of the hormone, melatonin, and for a component of hemoglobin called heme. Further, metabolism of a number of drugs and toxins by the liver requires coenzyme A .

Evidence from limited intervention studies suggests that pantothenic acid and/or pantothenol (alcohol analog) might improve the healing process of skin wounds.

Pantothenic acid is formed from b-alanine and pantoic acid. Pantothenate is required for synthesis of coenzyme A.

Coenzyme A was named for its role in acetylation reactions. Most acetylated proteins in the body have been modified by the addition of an acetate group that was donated by the coenzyme A thioester derivative, acetyl-CoA.

Coenzyme A structure

Food sources of pantothenic acid: eggs, fish, milk and milk products, whole-grain cereals, legumes, yeast, broccoli and other vegetables in the cabbage family, white and sweet potatoes, lean beef .

Deficiency of pantothenic acid is extremely rare due to its widespread distribution in whole grain cereals, legumes and meat.

Pyridoxine (B6)

PLP functions as a cofactor in enzymes involved in transamination reactions required for the synthesis and catabolism of the amino acids.

The many biochemical reactions catalyzed by PLP-dependent enzymes are involved in essential biological processes, such as hemoglobin and amino acid biosynthesis, as well as fatty acid metabolism. Of note, PLP also functions as a coenzyme for glycogen phosphorylase, an enzyme that catalyzes the release of glucose from stored glycogen. Much of the PLP in the human body is found in muscle bound to glycogen phosphorylase. PLP is also a coenzyme for reactions that generate glucose from amino acids, a process known as gluconeogenesis.

In the brain, the PLP-dependent enzyme aromatic L-amino acid decarboxylase catalyzes the synthesis of two major neurotransmitters: serotonin from the amino acid tryptophan and dopamine from L-3,4-dihydroxyphenylalanine (L-Dopa). Other neurotransmitters, including glycine, D-serine, glutamate, histamine, and γ-aminobutyric acid (GABA), are also synthesized in reactions catalyzed by PLP-dependent enzymes.

Pyridoxol, 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 (PLP).

Deficiencies of vitamin B6 are rare and usually are related to an overall deficiency of all the B-complex vitamins. Isoniazid and penicillamine (used to treat rheumatoid arthritis and cystinurias) are two drugs that complex with pyridoxal and pyridoxal phosphate resulting in a deficiency in this vitamin.

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Folic acid (B9)

The function of THF derivatives is to carry and transfer various forms of one carbon units during biosynthetic reactions. The one carbon units are either methyl, methylene, methenyl, formyl or formimino groups.

These one carbon transfer reactions are required in the biosynthesis of serine, methionine, glycine, choline and the purine nucleotides.

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Inadequate folate status during early pregnancy increases the risk of congenital anomalies. Yet, folate status is considered inadequate in a majority of women of childbearing age worldwide.

Clinical folate deficiency leads to megaloblastic anemia, which is reversible with folic acid treatment. Rapidly dividing cells like those derived from bone marrow are most vulnerable to the effects of folate deficiency since DNA synthesis and cell division are dependent on folate coenzymes. When folate supply to the rapidly dividing cells of the bone marrow is inadequate, blood cell division is reduced, resulting in fewer but larger red blood cells. This type of anemia is called megaloblastic or macrocytic anemia, referring to the enlarged, immature red blood cells.

Folic acid is a conjugated molecule consisting of a pteridine ring structure linked to para-aminobenzoic acid (PABA) that forms pteroic acid. Its coenzyme form is tetrahydrofolic acid (THF, tetrahydrofolate).

Folic acid is obtained primarily from yeasts and leafy vegetables as well as animal liver.

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Cobalamin (B12)

Vitamin B12 is synthesized exclusively by microorganisms and is found in the liver of animals bound to protein as methycobalamin or 5'-deoxyadenosylcobalamin. The vitamin is then bound by intrinsic factor (Kastle factor), a protein secreted by parietal cells of the stomach, and carried to the ileum where it is absorbed.

The vitamin B12 is necessary for purine and thymidine biosynthesis which are part of DNA.

The liver can store up to six years worth of vitamin B12, hence deficiencies in this vitamin are rare. Pernicious anemia is a megaloblastic anemia resulting from vitamin B12 deficiency that develops as a result a lack of intrinsic factor in the stomach leading to malabsorption of the vitamin. The anemia results from impaired DNA synthesis due to a block in purine and thymidine biosynthesis. The block in nucleotide biosynthesis is a consequence of the effect of vitamin B12 on folate metabolism.

Food sources of B12

Vitamin B12 is composed of a complex tetrapyrrol ring structure (corrin ring) and a cobalt ion in the center.

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Biotin

Biotin is an essential cofactor to enzymes in intermediary metabolism and a key regulator of gene expression.

Biotin is the cofactor required of enzymes that are involved in carboxylation reactions, e.g. acetyl-CoA carboxylase and pyruvate carboxylase.

Animal studies have shown that biotin sufficiency is essential for normal fetal development. Whether marginal biotin deficiency during pregnancy increases the risk for congenital anomalies in humans is currently an area of concern and investigation.

Definitive evidence that establishes whether biotin supplementation improves glucose and lipid homeostasis in individuals with type 2 diabetes mellitus is currently lacking, but suggestive observations have been published.

Biotin is found in numerous foods and also is synthesized by intestinal bacteria and as such deficiencies of the vitamin are rare. Deficiencies are generally seen only after long antibiotic therapies which deplete the intestinal fauna or following excessive consumption of raw eggs. The latter is due to the affinity of the egg white protein, avidin, for biotin preventing intestinal absorption of the biotin.