Chapter six Vitamins

Introduction
Vitamins are organic compounds that cannot synthesized by the human body (intestinal microorganisms) in sufficient amounts, therefore must be supplied by the diet. Vitamins are required in small quantities for normal growth, maintaining cellular functions and reproduction.

Vitamins can be classified into two groups based on their solubility: 1- Fat soluble vitamins. 2- Water soluble vitamins.

Fat soluble vitamins:

These are vitamins which insoluble in water but soluble in organic solvents like benzene, CCL4, CHCL3,. Fat soluble vitamins can be stored in the body, in liver. However, because fat soluble vitamins are storage, excessive intakes can result in toxic conditions (hyper vitaminoses).

Vitamin A:
Vitamin A is fat soluble vitamin and exists in three forms: retinol, retinal and retinoic acid. Vitamin A is found in animal sources such as liver, egg yolk and fish oil. Yellow and dark green vegetables and fruits are good dietary sources of the carotenes known as a pro vitamin A are a good source of vitamin A and cleaved in the small intestine by carotene dioxygenase yielding retinaldehyde which reduced to retinol and retinoic acid.

Dark green and yellow vegetables, such as carrots, tomatoes, and broccoli, are excellent sources of the precursor of vitamin A, -carotene.

- Carotene present in carrot, potatoes and tomatoes . Functions of vitamin A: 1- Vitamin A is critical for version

2- In the maintain of healthy epithelial tissues and skin. 3- Necessary for the synthesis of muco polysaccharides of the brain. 4- Have the role in reproduction system. 5- Involved in the electrons transport chain and oxidative phosphorylation. The current recommended dietary allowance (RDA) is 5000 I.U = 1g of retinol or 6 g of carotene.

Recommended Allowance
Life stage
Infants
Children Adult Pregnant women Lactating women

mg/day
400-500
300-600 900M- 700F 750-800 122-1300

Deficiency of vitamin A
Vitamin A is stored in the liver and deficiency of the vitamin occurs only after prolonged lack of dietary intake. Deficiency causes: 1- In children, lack of vitamin A leads to xerophthalimia, an eye disease that result first in night blindness and eventually in total blindness. 2- Scaly and rough. 3- Failure of growth in children. 4- Teeth become unhealthy due to thinning of enamel.

Toxicity of vitamin A
Because vitamin A is fat soluble and can be stored, primarily in the liver, routine consumption of large amounts of vitamin A over a period of time can result in toxic symptoms, including liver damage, bone abnormalities and joint pains, alopecia, Hair lose, double vision, nausea, headaches and vomiting, and skin desquamation

Vitamin D:
Vitamin D are a group of steroid compound that have a hormone like function. The best sources of vitamin D are fish, liver oil, egg, milk and sunlight induced synthesis of vitaminD3 in skin. There are two forms of vitamin D: vitamin D3 or (cholecalciferol) in animals and vitamin D2 or ergosterol in plant. Vitamin D3 is not active form of the vitamin D, but it is converted to active form by a series of reactions:

Physiology
PTH, Low Ca or Phos

T1/2-3 weeks
FGF23 from osteocytes

So..Exposure to Sun and Then, Fortified Foods.Give Us the D We Need

Functions of Vitamin D
Vitamin D plays a major role in the regulation of calcium levels and therefore is required for the proper formation of bone and teeth.
More recently suggested to affect a wide-range of diseases, including autoimmune disorders, cancer, metabolic syndrome Vitamin D is known to modulate immune function in humans.

Once joined with ingested vitamin D, facilitate increased serum calcium levels . Shows Expressed Calbindins and How the facilitate transport of Calcium through the Membranes

Deficiency of vitamin D:
Vitamin D deficiency in nutrition causes Rickets in children and osteomalacia in adults, bone pain, muscle weakness. Liver disease and kidney failure leads to decrease formation of active form of vitamin D. This vitamin with parathyroid hormone stimulates the reabsorption of calcium so that it is not lost in the urine, therefore, lack of parathyroid hormone causes hypocalcemia.

Toxicity of vitamin D:
Vitamin D is fat soluble, and can be stored in the body and high doses of vitamin D can causes loss of appetite, nausea, and thirst. Enhance calcium absorption and bone resorption causes hyper calcemia, which can be lead to deposition of calcium in many organs particularly kidney and arteries.

What about Sun Safety?

UV light is required to make vitamin D and prolonged exposure to can cause damage to skin cells Sun cream also drastically lowers the amount of UV light entering skin Just 15 minutes in the sun a day is enough!
People with darker skins may need longer

What can we do?

Encourage exposure to sunlight!

Vitamin E:
Vitamin E refers to a family of seven compounds called tocopherol (alfa, beta, gama, delta, epsa, zeta, eta, which differ in the number and position of the methyl group on the ring), in which - tocopherol is the active form.

Tocopherols
R1 HO C H3 R2 R3 O C H3 C H3 C H3 C H3

Trivial Name
-Tocopherol -Tocopherol -Tocopherol -Tocopherol

Chemical Name
5,7,8-Trimethyltocol 5,8-Dimethyltocol 7,8-Dimethyltocol 8-Methyltocol

R1
CH3 CH3 H H

R2
CH3 H CH3 H

R3
CH3 CH3 CH3 CH3

The major sources of vitamin E are vegetable oils and some fruits like olive and palm, also present in small amount in meat, milk, and eggs.

Functions of vitamin E
The primary function of vitamin E is as an antioxidant in prevention of the nonenzymic oxidation of cell components, for example, polyunsaturated fatty acids and other components of cell membranes, erythrocyte membrane and low-density lipoprotein (LDL) from oxidation, by molecular oxygen and free radicals.

Deficiency of Vitamin E:
The major symptom of vitamin E deficiency in human is hemolytic anemia due to increased red blood cell fragility. Also deficiency of this vitamin leads to increased oxidation of polyunsaturated fatty acids in the muscle with a rise in O2 consumption and peroxide production, peroxide leads to hydrolysis of intracellular.

Toxicity of vitamin E:
Vitamin E does not seem to have toxic effects in high doses.

Recommended Dietary Allowance (RDA) for vitamin E was 10 mg (15 I.U.) for men and 8 mg (12 I.U.) for women.

Table 1: Recommended Dietary Allowances (RDAs) for Vitamin E (Alpha-Tocopherol) [6] Age 0-6 months* Males 4 mg (6 IU) 5 mg (7.5 IU) 6 mg (9 IU) Females 4 mg (6 IU) 5 mg (7.5 IU) 6 mg (9 IU) Pregnancy Lactation

7-12 months*

1-3 years

4-8 years

7 mg (10.4 IU)
11 mg (16.4 IU) 15 mg (22.4 IU)

7 mg (10.4 IU)
11 mg (16.4 IU) 15 mg (22.4 IU) 15 mg (22.4 IU) 19 mg (28.4 IU)

9-13 years

14+ years

Vitamin K:
There are three forms of vitamin K: VitaminK1 (Phylloquinone) derived from plants (is found in green vegetables like spinach and tomatoes. Vitamin K2 (Menaquinone) produced by intestinal bacteria Vitamin K3 (Menadione) produced by alkylation of Vitamin K2.

Vitamin K1

"n" can be 6, 7 or 9 isoprenoid groups Vitamin K3

Vitamin K2

Functions of Vitamin K
Vitamin K is required in the hepatic synthesis of prothrombin and blood clotting factors II, VII, IX, and X. These proteins are synthesized as inactive precursor molecules. Formation of the clotting factors requires the vitamin K dependent carboxylation of glutamic acid residues to Gla residues. This forms a mature clotting factor that contains Gla and is capable of subsequent activation. The reaction requires O2, CO2, and the hydroquinone form of vitamin K.

The Gla residues of prothrombin are binds with calcium ions to produce prothrombin calcium complex, The prothrombincalcium complex is then able to bind to phospholipids essential for blood clotting on the surface of platelets. Attachment to the platelet increases the rate at which the proteolytic conversion of prothrombin to thrombin can occur

Deficiency of Vitamin K:
Vitamin K is widely distributed in nature and its production by the intestinal bacteria ensures that dietary deficiency does not occur. Vitamin K deficiency however is found in: 1- Patients with liver disease and biliary obstruction due to intestinal of entry of the bile salts to the intestine. 2- In new born infants, due to absence of intestinal bacteria flora. 3- Prolonged antibiotic therapy will kill the intestine bacteria. 4- Malabsorption of dietary lipids.

Adequate Intake (AI) for Vitamin K

Life Stage Infants Infants Children Children Children Adolescents Adults Pregnancy Pregnancy Breast-feeding Breast-feeding Age 0-6 months 7-12 months 1-3 years 4-8 years 9-13 years 14-18 years 19 years and older 18 years and younger 19 years and older 18 years and younger 19 years and older Males (mcg/day) 2.0 2.5 30 55 60 75 120 Females (mcg/day) 2.0 2.5 30 55 60 75 90 75 90 75 90

Water soluble vitamins:

The water soluble vitamins are a group of compounds which function as coenzymes for metabolic reactions.

Overview of Water-Soluble Vitamins

Water soluble vitamins dissolve in cooking water therefore Found in watery components of food Subject to cooking losses Function as a coenzyme Move directly into blood when absorbed Kidneys capable of removing small excesses Large excesses overwhelm system and may cause toxicity Participate in energy metabolism 50-90% of vitamins are absorbed

Vitamin C:
Vitamin C is found in vegetables like green pepper, spinach, tomatoes, and potatoes and in citrus fruits such as orange, lemon, and pineapple. Vitamin C is also called ascorbic acid (active form), the main function of vitamin C acts as a natural antioxidant. It destroys free radicals due to its reducing agents in several different reactions. Easily lost through cooking and Sensitive to heat, copper, and oxygen

Vitamin C or ascorbic acid is a coenzyme in the hydroxylation of lysine and proline, and these compounds are essential for the production of collagen: most abundant protein in body, present in connective tissue. Also protects immune system. Ascorbic acid reduces the dietary ferric iron to ferrous iron which can be absorbed from the intestine. Ascorbic acid is helping the enzyme folate reductase to reduce folic acid to tetra hydro folate (active form). Thus it helps the maturation of RBC.

Vitamin C is synthesized by most animals (not by human).

BIOSYNTHESIS OF VITAMIN C
Glucose

D - Glucuronate
L - Gulonate L - Gulonolactone
L - gulonolactone oxidase

3 - Keto - L - gulonolactone L - Ascorbic acid

70

Distribution of Antioxidants

Intracellular
CAT
SOD GPX

tocopherols Lipoprotein coenzyme Q Extracellular carotenoids

SOD SOD

superoxide dismutase (SOD) glutathione peroxidase (GPX) catalase (CAT)

glutathione ascorbic acid flavonoids uric acid

B- Complex vitamins:

How B Vitamins Function as Coenzymes

B Vitamin Roles in Metabolism

The B Vitamins
Coenzymes

1- Thiamine (vitamin B1):

Thiamine, also known as vitamin B1, it is abundant in liver, meat, milk, cereals, heart, kidney, whole grain and green leafy vegetables.

Thiamin Sources

Thiamine reacts with ATP to form thiamine pyrophosphate (TPP), the active coenzyme form of thiamine.

Thiamine pyrophosphate is a coenzyme involved in several enzymatic reactions mainly for: TPP serves as coenzyme for pyruvate and keto glutarate dehydrogenases catalyzed oxidative decarboxylation reaction Coenzyme in transketolase catalyzed reactions of pentose phosphate pathway of -keto carboxylic acids.

The main role of TPP is in carbohydrate metabolism. So, the required of thiamine is increased along with higher intake of carbohydrates.

Function of Thiamin

Deficiency of thiamine:
Thiamine deficiency leads to failure of carbohydrate metabolism, resulting in decreased production of ATP and thus impaired cellular functions of central nervous, heart and gastrointestinal tract. Also thiamine deficiency lead to beriberi, a disease characterized by muscle weakness, mental stability, poor appetite, deep muscle pain and pain on contact with the skin.

RDA For Thiamin

1.1 mg/day for women 1.2 mg/day for men Most exceed RDA in diet Surplus is rapidly lost in urine; non toxic

Riboflavin (vitamin B2):

Rich source of riboflavin are liver, heart, kidney, milk, egg, whole cereals, fish, green leafy vegetable and some fruits.

When riboflavin is phosphorylated in the present of ribokinase enzyme, it gets converted to two active coenzymes, Flavin Mono Nucleotide (FMN) in the intestinal mucosal cells and Flavin Adenine Di nucleotide (FAD) in the liver: which are used in energy metabolism.

Riboflavin

Copyright 2005 Wadsworth Group, a division of Thomson Learning

FMN and FAD serve as coenzymes for several oxidation reduction reactions in metabolism. For example FAD is a cofactor for pyruvate dehydrogenase complex (PDH), and also for succinate dehydrogenase in TCA cycle. FMN and FAD are each capable of reversibly accepting two hydrogen atoms, forming FMNH2 and FADH2. Riboflavin are involved in the metabolism of iron, pyridoxine, folate, also involved in protection against peroxidation in metabolism of xenobiotics.

Enzymatic processes of flavin nucleotides

Deficiency of riboflavin:
Plants, microorganisms and intestinal micro flora synthesize riboflavin. Hence dietary deficiency is rare. But deficiency of other vitamins is a accompanied by riboflavin deficiency beriberi, pellagra. Deficiency symptoms include dermatitis, cheilosis (fissuring at the corners the mouth) and glossitis (the tongue appearing smooth and purplish.

RDA for Riboflavin

1.1 mg/day for women 1.3 mg/day for men Toxicity not documented

Niacin:
Niacin (nicotinic acid and nicotinamide) is also known as vitamin B3 and found in the liver, meat and milk. Limited quantities of niacin can be obtained from the metabolism of tryptophane.

Nicotinamide

Nicotinic acid

Niacin is an essential precursor for the coenzymes: Nicotinamide Adenine Dinucleotide (NAD) Nicotinamide Adenine Dinucleotide Phosphate (NADP)

NAD and NADP are involved in oxidation reduction reactions catalyzed by dehydrogenases. They are therefore have role in carbohydrate, lipids, and protein metabolism. For example:

A disease involving the skin, gastrointestinal tract and central nervous system.

PELLAGRA

Also deficiency of V.B6 (pyridoxal phosphate) leads to deficiency of niacin, because it is involved as coenzymes in the pathway of synthesis of niacin from tryptophane.

Vitamin B6 (pyridoxine):
Vitamin B6 is found in many foods, such as fish, meat, milk, egg, green leafy vegetables and potatoes. Vitamin B6 can be synthesized by the intestinal bacteria. Vitamin B6 consists of three related pyridine derivatives; pyridoxine, pyridoxal, and pyridoxamine.

Vitamin B6 converted to the coenzyme pyridoxal phosphate (PLP) from phosphorylation of all three forms of this vitamin.

Pyridoxal phosphate (PLP) is required in the transamination of amino acids and decarboxylation of carboxylic acids. PLP acts as coenzyme for over 100 enzymes in protein metabolism, needed to: -amino acid and fatty acid metabolism which helps to convert tryptophan to niacin and to serotonin also helps to make red blood cells. -Keep immune and nervous systems healthy -Metabolize fats and carbohydrates and break down Glycogen

Deficiency of vitamin B6:

The deficiencies of vitamin B6 is rare but have been observed in women taking oral contraceptive, alcoholics (due to poor diet and alcohol causes body to lose B6) and used of some drugs like pencillamide which combine with pyridoxal phosphate forming inactive derivatives of pyridoxal phosphate. Deficiency of pyridoxine may lead to dermatitis, and anemia.

RDA of Vitamin B6 (pyridoxine):

Daily needs: men 1.3-1.7 mg/day; women 1.3-1.5mg/day, depending on age

Pantothenic acid:
The important sources of pantothenic acid are liver, egg, yeast, potatoes, tomatoes and skimmed milk, although the vitamin is widely distributed.

Pantothenic acid is a component of coenzyme A (CoA-SH) and acyl carrier protein (ACP). The thiol group of CoA-SH and ACP acts as a carrier of acyl groups. Coenzyme A is required for the metabolism of all fat, protein, and carbohydrate via the citric acid cycle.

Deficiency of pantothenic acid:

Pantothenic acid deficiency is not well characterized in human because it is widespread in natural foods and when pantothenic deficiency dose occur, it is usually associated with multiple nutrient deficiencies, thus making it difficult to discern symptoms specific to the pantothenic acid.

Biotin:
Biotin is found in liver, kidney yeast, milk, egg yolk, soya bean, tomatoes and vegetables. Also intestinal bacteria provide sufficient amounts of biotin.

The active coenzyme form of biotin is biotin itself. It is a coenzyme involved in carboxylation reactions in the metabolism of fats, carbohydrates and protein.

RDA FOR Biotin

Daily needs for adults: 30 g/day

Deficiency of biotin:
Deficiency of biotin is rare in human because it is widely distributed in foods. But deficiency of biotin occurs in consuming large amounts of raw egg white, because egg white contains a glycoprotein avidin which binds to biotin and prevent biotin absorption. Also intake sulphonamide drugs or oral antibiotics for prolonged periods, that inhibit the growth of intestinal bacteria, eliminate this source of biotin and lead to biotin deficiency. The biotin deficiency leads to dermatitis, loss of hair, decrease in weight, sleepiness, depress and nausea.

Lipoic acid:
Lipoic acid is found in yeast, liver, and the compound occurs widely in nature. Lipoic acid exists in oxidized and reduced form. Lipoic acid functions as a coenzyme in pyrovate dehydrogenase multi enzyme complex and - ketoglutarate dehydrogenase multi enzyme complex.

Lipoamide contains sulfurs that can be reversibly oxidized or reduced.

Deficiency of lipoic acid:

A deficiency of lipoic acid usually does not occur because it is widespread in the nature.

Folic acid:
Folic acid is widely distributed in the word. A good source of this vitamin are liver, kidney, green leafy vegetables, tomatoes, potatoes, Folic acid is converted to its active coenzyme tetrahydrofolate (THF) or (FH4).

Folate Sources

positions 7 and 8 carry hydrogens in dihydrofolate (DHF) positions 58 carry hydrogens in tetrahydrofolate (THF)

Tetrahydro folate act as a carrier of one carbon unit (may be methyl -CH3, methylene -CH2, formyl -CHO, formate-COOH.) during metabolism. FH4 is used in the synthesis of purines and pyrimidines, and therefore for the formation of DNA and RNA in all cells including maturing blood cells- synthesis of RBC and WBC. Also FH4 is needed for the synthesis of amino acid methionine.

Deficiency of folic acid:

Folic acid deficiency leads to megaloblastic anemia, caused by decreasing synthesis of purine and pyrimidine, which inhibits DNA synthesis. This leads to change in size and shape of the nuclei and slower maturation of red blood cells, causing production of abnormality large red blood cells with fragile membranes. Also folate deficiency leads to glossistis and gastero intestinal disorders. Folic acid is especially necessary for children and pregnant women

Folate

Folate deficiency results in macrocytic anemia.

Cobalamin (Vitamin B12)

Dietary source of vitamin B12 are of animal origin and include meat, eggs, milk, fish,.Vitamin B12 is absent in plant foods. Human obtain small amounts of this vitamin from their intestinal flora.

Cobalamine exists in three forms that differ in the group attached to cobalt. The active coenzyme forms of vitamin B12 are methyl cobalamine and deoxyadenosyl cobalamine.

Cobalamin (Vitamin B12) is a coenzyme for enzymes that transfer methyl groups and produce red blood cells. Vitamin B12 is the only water soluble vitamin that is stored in significant amounts in the liver, bone marrow and other tissues.

vitaminB12 coenzyme-dependent enzymes

: Murray et al, 1996

153

Deficiency of vitamin B12:

Deficiency of this vitamin is not observed because it is widespread in foods of animal origin. Vitamin B12 deficiency causes folate deficiency (because the generation of FH4 depends on the presence of Vitamin B12), therefore, all the manifestation of folate deficiency are also seen.

Also the deficiency causes pernicious anemia, a disease that is characterized by the presence of large, immature of red blood cells in the blood. Symptoms include a sore tongue, weight loss, mental and nervous disorder. The damage to the central nervous system can even cause demyelination of the peripheral nerves in the arms and legs. Eventually, this can progress to the spinal cord.

Metabolic Pathways Involving B Vitamins

Controversy:

Vitamin Supplements: Do the Benefits Outweigh the Risks?

Which is the best source?