BIOCHEMISTRY OF FAT SOLUBLE VITAMINS: CLASSIFICATION, STRUCTURE, COENZYME FORMS, BIOLOGICAL ACTION, DAY NECESSITY, SOURSES. PROVITAMINS. HYPO- AND HYPERVITAMINOSIS.

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 retinol, the form most common in mammalian tissues and marine fishes, and vitamin, A₂, common in freshwater fishes. Both are isoprenoid compounds containing a six-membered carbocyclic ring and an eleven-carbon side chain.

http://www.youtube.com/watch?v=dcw1m31zuTE

Vitamin A

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

All-trans-retinal	11-cis-retinal

Retinol	Retinoic Acid

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 symmetrical 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 thickened, the kidneys and various glands degenerate, and both males and females become sterile.

Although all tissues appear to be disturbed by vitamin A deficiency, the eyes are most conspicuously affected. In infants and young children the condition known as xerophthalmia ("dry eyes") is an early symptom of deficiency and is a common cause of blindness in some tropical areas where nutrition is generally poor. In adults an early sign of vitamin A deficiency is nightblindness, a deficiency in dark adaptation, which is often used as a diagnostic test.

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 impaired by vitamin A deficiency. Cone cells, which sense colors, are adapted for high light intensities.

Retinal rod cells contain many membrane 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 undergoes transformation into all-trans-retinal, which causes a substantial change in the configuration of the retinal molecule. This reaction is nonenzymatic. The isomerization of retinal is followed by a series of other molecular changes, ending in the dissociation of the rhodopsin to yield free opsin and all-trans-retinal, which functions as a trigger setting off the nerve impulse.

11-cis-retinal all-trans-retinal

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 enzymatic reactions catalyzed by two enzymes:

retinal-reductase

all-trans-retinal + NADH + H⁺ → all-trans-retinol + NAD⁺

retinol-isomerase

all-trans-retinol → 11-cis-retinol

retinal-reductase

11-cis-retinol + NAD⁺ → 11-cis-retinal + NADH + H⁺

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 transport of Ca²⁺ across certain membranes; such a more general role might explain the effects of vitamin A deficiency and excess on bony and connective tisues;

- processes of growth and cell differentiation;

- processes of glycoproteins formation whoch are the components of the biological mucosa .

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.

Vitamin D is a steroid hormone that functions to regulate specific gene expression following interaction with its intracellular receptor. The biologically active form of the hormone is 1,25-dihydroxy vitamin D₃ (1,25-(OH)₂D₃, also termed calcitriol). Calcitriol functions primarily to regulate calcium and phosphorous homeostasis.

http://www.youtube.com/watch?v=JwPVibQ6_3Y&feature=related

http://www.youtube.com/watch?v=onSPZ0aBUKM&feature=related

http://www.youtube.com/watch?v=xwNhd2pQL0k&feature=related

Ergosterol	Vitamin D2

7-Dehydrocholesterol	Vitamin D3

Cholecalciferol is converted into its derivative - 25-hydroxycholecalciferol. This product is more active biologically than cholecalciferol and it has been found to be the main circulating form of vitamin D in animals, formed in the liver. But 25-hydroxycholecalciferol was found to be metabolized further to 1,25-dihydroxycholecalciferol in kidneys. This compound is still more active; its administration produces rapid stimulation of Ca²⁺ absorption by the intestine.

25-hydroxyvitamin D3	1,25-dihydroxyvitamin D3

So the kidney is the site of formation of 1,25-dihydroxycholecalciferol, which now appears to be the biologically active form of vitamin D, capable of acting directly on its major targets, the small intestine and the bones.

1,25-dihydroxycholecalciferol promotes absorption of Ca²⁺ from the intestine into the blood, through its ability to stimulate the biosynthesis of specific protein(s) that participate in transport or binding of Ca²⁺ in the intestinal mucosa. This role of 1,25-dihydroxycholecalciferol is integrated with the action of parathyroid hormone. Whenever the Ca²⁺ concentration of the blood becomes lower than normal, the parathyroid glands secrete larger amounts of parathyroid hormone. This hormone acts on the kidney, stimulating it to produce more 1,25-dihydroxycholecalciferol from its precursor 25-hydroxycholecalciferol.

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

http://www.youtube.com/watch?v=n7vybcT9_F4

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.

About 2,5-10 mkg of vitamin D is required by an adult daily and 12-25 mkg by children. The vitamin can be stored in sufficient amounts in the liver for a single dose to suffice for some weeks.

Vitamin E

a-Tocopherol

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 tocopherols having vitamin E activity have been found in plants; the most active and abundant is a-tocopherol.

The deficiency of tocopherol produces many other symptoms besides infertility in male and female, e.g., degeneration of the kidneys, the deposition of brown pigments in lipid depots, necrosis of the liver, and dystrophy, or wasting, of skeletal muscles.

Tocopherols have been found to have antioxidant activity; i.e., they prevent the autoxidation of highly unsaturated fatty acids when they are exposed to molecular oxygen. One of the functions of tocopherol may be to protect highly unsaturated fatty acids in the lipids of biological membranes against the deleterious effects of molecular oxygen. Normally, autoxidation products of unsaturated fats do not occur in the tissues, but in tocopherol deficiency they are detectable in the fat depots, liver, and other organs.

Due to the hydrophobic side radical tocopherol can be built into the phospholipid matrix of biological membranes and stabilize the mobility and microviscosity of membrane proteins and lipids.

Tocopherol is the most potent natural antioxidant.

About 10-20 mg of vitamin E is required per day.

The most abundant sources of vitamin E are oils (sunflower, corn, soybean oils), fresh vegetables, animal stuffs (meat, butter, egg yoke).

http://www.youtube.com/watch?v=8oRUF_g-J3k&feature=related

Vitamin K

The K vitamins exist naturally as K₁ (phylloquinone) in green vegetables and K₂ (menaquinone) produced by intestinal bacteria and K₃ is synthetic menadione. When administered, vitamin K₃ is alkylated to one of the vitamin K₂ forms of menaquinone.

Vitamin K1	Vitamin K2	Vitamin

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 synthesized by intestinal bacteria.

http://www.youtube.com/watch?v=DVGsnlVCoeA

http://www.youtube.com/watch?v=WI24c2LYFug&feature=related

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 reactions involved in the formation of prothrombin, the precursor 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 the antivitamin 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.

Function

• aids in reducing excessive menstrual flow
• aids the absorption of calcium in bone
• essential for normal liver functioning
• essential for synthesis of four proteins that act in coagulation
• important in maintaining vitality and longevity
• necessary for formation of prothrombin which is required for  effective blood clotting
• involved in electron transport mechanism and oxdative phosphorylation

Food Source

• alfalfa
• blackstrap molasses
• broccoli
• Brussels sprouts
• cauliflower
• cereals
• cow's milk
• egg yolks
• fish liver oils
• green plants, such as lettuce
• kelp
• leafy green vegetables, such as cabbage, spinach
• meats, such as pig and beef liver
• peas
• polyunsaturated oils
• potatoes
• string beans
• yogurt

Effective With

Increased Intakes Needed

• after prolonged paraffin ingestion
• for those with biliary obstructions
• for those with liver disease
• if taking antibiotics for long duration
• if you have a malabsorption disease
• in newborn babies
• in overdose of anticoagulant drugs, such as Warfarin, Dicoumarol, which neutralize the effect of Vitamin K

Used For

• anticoagulant drug overdose
• hemorrhagic disease in newborn babies
• inhibiting some cancer tumors
• overcoming inability to absorb vitamins
• overcoming effects of antibiotics on intestinal bacteria
• protection against osteoporosis

Destroyed By

• acids
• alkalis
• commercial processing
• light and ultra-violet irradiation
• oxidizing agents

Symptoms of Deficiency

• excessive bleeding and hemorrhage

In babies:

• bleeding from the stomach, intestines, umbilical cord site

Deficiency Caused By

In Babies:

• low levels in human breast milk
• poor transfer across placenta
• sterile intestine with no bacteria

In Adults:

• as a consequence of sprue
• Celiac's Disease
• destruction of intestinal bacteria by antibiotics
• lack of bile salts
• liver conditions, such as viral hepatitis
• surgical removal of intestines
• prolonged ingestion of liquid paraffin

Deficiency Leads To

• inability of blood to coagulate

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.