fat soluble vitamins vitamin a vitamin e vitamin d vitamin k

58
Fat Soluble Vitamins Vitamin A Vitamin E Vitamin D Vitamin K

Upload: monty

Post on 19-Jan-2016

162 views

Category:

Documents


9 download

DESCRIPTION

Fat Soluble Vitamins Vitamin A Vitamin E Vitamin D Vitamin K. Vitamin A. RETINOIDS. The retinoids : a family of molecules that are related to retinol (vitamin A) ------------------------------------- The term retinoids includes - PowerPoint PPT Presentation

TRANSCRIPT

Page 1: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Fat Soluble Vitamins

Vitamin AVitamin EVitamin DVitamin K

Page 2: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Vitamin A

Page 3: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

RETINOIDS

The retinoids: a family of molecules that are related to

retinol (vitamin A)

-------------------------------------

The term retinoids includes

natural & synthetic forms of vitamin A that may or may not show vitamin A activity

Page 4: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K
Page 5: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Retinoids

1- Retinol

A primary alchol containing -ionone ring with an unsaturated side chain. It is found in animal tissues as a retinyl ester with long-chain fatty acids.

2- Retinal

The aldhyde derived from the oxidation of retinol. Retinol and retinal can be interconverted.

Page 6: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

3- Retinoic acid

The acid derived from oxidation of retinal. It can not be reduced in the body, and therefore, can not give rise

to either retinal or retinol

4- -carotene

Plant foods contain -carotene, which can be oxidatively cleaved in the intestine to yield two molecules of retinal

In humans, the conversion is insufficient, and vitamin A activity of -carotene is only about one sixth of that of retinol

Page 7: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Absorption & Transport of vitamin A

Transport to the Liver

I- Retinol is derived from (DIET SOURCES) 1- DIET Retinyl esters (animal source) which are hydrolyzed in the intestinal mucosa, releasing retinol and free fatty acids

2- DIET -carotenes (plant source) which is cleaved 2 retinal retinol

II- Retinol is esterified with fatty acids to give retinyl esters

III- Retinyl esters are collected by the chylomicrons into the lymphatic system.

IV- Retinyl esters contained in the chylomicrons are taken up and stored by the liver

Page 8: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Release from the Liver

• When needed, retinol is released from the liver and transported to extra hepatic tissue by plasma retinol binding protein (RBP)

• The retinol - RBP complex attaches to specific receptors on the surface of the cells of peripheral tissues permitting retinol to enter

Page 9: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K
Page 10: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Mechanism of Action of vitamin A

• Retinol is oxidized to retinoic acid inside cells.

• Retinoic acid binds with high-affinity to specific receptor proteins present in the nucleus of target tissue, such as epithelial cell.

• The activated retinoic acid - receptor complex interacts with nuclear chromatin (genes) to stimulate retinoid-specific mRNA synthesis, resulting in the production of specific proteins that mediate several physiological functions.

e.g. retinoids control the expression of keratin gene in most epithelial tissues.

Page 11: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K
Page 12: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Functions of Vitamin A

• Vision

• Growth

• Reproduction

• Epithelial cells maintenance

Page 13: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Functions of Vitamin A

1- Vision

• Vitamin A is a component of the visual pigments of rod and cone cells.

• Rhodopsin, the visual pigment of the rod cells in the retina, (for vision in dim light) consists of 11-cis retinal specially bound to the protein opsin.

• When rhodopsin is exposed to light, a series of photochemical isomerization occurs,

which results in release of all trans retinal and opsin (with bleaching of the visual pigment).

• This process triggers a nerve impulse that is transmitted by the optic nerve to the brain.

• Regeneration of rhodopsin requires isomerization of all trans retinal back to 11-cis retinal, which spontaneously combines with opsin to form rhodopsin.

Page 14: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

2- Growth

• Vitamin A is essential for normal growth of cells

(by synthesis of important proteins)

• bone growth is slow in vitamin A deficiency.

• Animals deprived of vitamin A suffers keratinzation of taste buds leading to losing of their appetites.

Page 15: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

3- Reproduction

• Retinol & retinal are essential for normal reproduction 1- supporting spermatogenesis in males 2- preventing fetal resorption in females

• Retinoic acid is inactive in maintaining reproduction & the visual cycle, BUT promotes growth.

Thus, retinoic acids given only since birth to animals, leads to blindness & sterility.

4- Epithelial cells maintenance

• Vitamin A is essential for normal differentiation of epithelial tissues and mucus secretion.

Page 16: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Distribution of Vitamin A

• Sources of retinol (retinyl esters) : animal source Liver, kidney, cream, butter & egg yolk

• Sources of carotenes (precursors of vitamin A) : plant source Yellow & dark green vegetables & fruits

Requirement for Vitamin A

• One RE (retinol equivalents) = 1 g of retinol 6 g of -carotene 12 g of other carotenoids

• RDA for adults 1000 RE for males 800 RE for females

Page 17: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Clinical indications

1- Dietary deficiency

Vitamin A, administered as retinol or retinyl esters, is used to treat patients

deficient in the vitamin (not retinoic acid)

Night blindness

One of the earliest signs of vitamin A deficiency Difficulty in seeing in dim light. Prolonged deficiency leads to irreversible loss of visual cell. (affection of rods of retina)

Xerophthalmia

Severe deficiency of vitamin A Pathological dryness of the epithelium conjunctiva & cornea. It may end in corneal ulcerations and blindness.

Page 18: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

2- Acne & Psoriasis

Dermatologic problems of acne and psoriasis are effectively treated

with retinoic acid or its derivatives.

• Mild cases of acne is treated by topical application of tretinoin (All trans retinoic acid)

which is too toxic for systemic administration.

• Severe recalcitrant cystic acne unresponsive to conventional

therapies, isotretinoin (13-cis retinoic acid) is administered orally

Page 19: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

3- Prevention of chronic diseases

• Populations consuming diets high in -carotene show decreased incidence of heart diseases & lung & skin cancer

• Consumption of foods rich in -carotene is associated with reduced risk of cataracts and macular degeneration

Page 20: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Toxicity of Retinoids

I. Vitamin A excess (hypervitaminosis A syndrome) Amounts exceeding 7.5 mg/day of retinol

1- Excessive intake of vitamin A may cause the followings:

• dry skin & pruiritis are early signs• liver enlarged, cirrhotic• increased intracranial pressure (mimic symptoms of brain

tumours e.g. headache etc…)

2- Pregnant females should not ingest excessive amounts of vitamin A because of its potential for causing congenital malformations in developing fetus.

Page 21: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

II. Isotretinoin drug (13-cis retinoic acid) 1- Teratogenic

• So, absolutely contraindicated in women with childbearing potential. • Pregnancy should be excluded before initiation of treatment & adequate contraceptive (birth control) must be used

2- Risk of coronary heart diseases Prolonged treatment with 13-cis retinoic acid leads to hyperlipidemia & increase in LDL/HDL ratio with increased risk of coronary heart diseases.

Page 22: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Vitamin E

Page 23: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Vitamin E

• E vitamins consist of 8 naturally occurring tocopherols, of which - tocopherol is the most active.

• The primary function of vitamin E is an antioxidant in prevention of the nonenzymic oxidation of cell components as polyunsaturated fatty acids by molecular O2 & free radicals.

Page 24: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Distribution & requirements of vitamin E

• Vegetable oils are rich sources (plant sources)• Liver & eggs contain moderate amounts (animal sources)

• RDA for -tocopherol is 10 mg for men

8 mg for women

• Requirement is increased with increased intake of polyunsaturated fatty acids.

Page 25: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Deficiency of vitamin E

• Deficiency of vitamin E is almost entirely restricted to

premature infants.

• In adults, it is usually associated with defective lipid

absorption or transport.

• Signs of vitamin E deficiency include sensitivity of RBCs to peroxide & appearance of abnormal cellular

membrane.

Page 26: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Clinical indications

Vitamin E is not recommended for the prevention of

chronic disease, such as coronary heart disease or cancer.

Subjects in the Alpha-Tocopherol, Beta Carotene Cancer

Prevention Study trial who received high doses of vitamin

E, not only lack cardiovascular benefit but also had an

increased incidence of stroke.

Toxicity of vitamin E: no toxicity at 300mg / day dose

Page 27: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Vitamin D

Page 28: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Vitamin D

• The D vitamins are a group of sterols that have a hormone-like function.

• The active molecule, 1,25-dihydroxycholecalciferol (1,25-di OH D3 ), binds to intracellular receptor protein.

• The 1,25-diOH D3 - receptor complex interacts with DNA in the nucleus of target cells, and either stimulates gene expression, or represses gene transcription.

• The main actions of 1,25-diOH D3 are to regulate plasma levels of calcium & phosphorous.

Page 29: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Distribution of vitamin D: (Sources)

1- Diet

• Ergocalceferol (vitamin D2 ) is found in plants• Cholecalceferol (vitamin D3 ) is found in animal tissues.

2- Endogenous vitamin precursors

7-Dehydrocholesterol, is converted to cholecalceferol (vitamin D3) in the dermis and epidermis of human skin exposed to sunlight. Individuals with limited exposure to sunlight require performed vitamin D

Page 30: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K
Page 31: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Metabolism of vitamin D

1- Formation of 1, 25 dihydroxycholecalceferol (1,25-diOH D3)

• Vitamin D2 & D3 are not biologically active

• but are converted in vivo to the active form of D vitamin by two sequential hydroxylation reactions (two hydroxylases) that require monooxygenase, molecular oxygen and NADPH.

The two hydroxylases uses cytochrome P450

Page 32: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

First Hydroxylation

• occurs at the position 25

• catalyzed by a specific hydroxylase in the liver

• to give 25 hydroxycholecalceferol (25-OH D3)

- the predominant form of vitamin D in plasma

- the major storage form of the vitamin

Page 33: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Second Hydroxylation

• 25-OH D3 is further hydroxylated at position 1 • by the enzyme specific 25-hydroxycholecalceferol 1-hydroxylase • found primarily in the kidney

• resulting in the formation of 1, 25 dihydroxycholecalceferol (1,25 diOH D3)

is the most active vitamin D metabolite

Page 34: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

2- Regulation of 1-hydroxylase • Its formation is regulated by the level of plasma calcium and phosphate levels in plasma.

• 1-hydroxylase activity is increased: • DIRECTLY by low phosphate

• INDIRECTELY by low calcium levels (hypocalcemia) release of Parathyroid Hormone (PTH)

activation of 1 hydroxylase

increased production of 1,25-di(OH) D3

Page 35: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K
Page 36: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Function of Vitamin D

The overall function of 1,25-diOH D3 is to maintain adequate plasma levels of calcium.

It performs this function by

• increasing uptake of calcium by the intestine

• minimizing loss of calcium by the kidney

• stimulating resorption of bone (when necessary)

Page 37: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

1- Effect of vitamin D on INTESTINE:

• 1, 25-diOH D3 stimulates intestinal absorption of calcium & phosphate.

• 1,25-diOH D3 enters intestinal cell and binds to cytosolic receptor

1,25-diOH D3 – receptor complex

to nucleus

selectively interacts with DNA

increased synthesis of specific calcium-binding protein

enhanced Calcium Uptake

Page 38: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K
Page 39: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

2- Effect of vitamin D on BONE:

1,25-diOH D3 stimulates the mobilization of calcium and phosphate

from bone by a process that requires PTH

increase in plasma calcium & phosphate

Page 40: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Distribution & Requirement of vitamin D

• Vitamin D (Cholecalcerferol)

occurs naturally in fatty fish, liver, and egg yolk.

• Milk is not a good source for vitamin D (unless if fortified).

• The RDA for adults is 200 IU vitamin D

[available in 5 g cholecalceferol (vitamin D3)]

Page 41: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Clinical indications

1- Nutritional Rickets

Vitamin D deficiency

net demineralization of bone

Rickets (in children) Osteomalacia (in adults)

Page 42: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Ricketsthe continued formation of the collagen matrix

BUTincomplete mineralization

soft bones

deformity

Osteomalacia

demineralization of preexisting bones

susceptibility to fracture

Page 43: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Causes of vitamin D deficiency (one or both of the following causes)

1- Insufficient exposure to daylight (sunlight).

2- Deficiencies in vitamin D consumption

In areas where sunlight is not sufficient

RDA should be increased up to 800 IU/day instead of 200 IU/day (5 g cholecalceferol)

to reduce the incidence of osteoprotic fractures

Page 44: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

2- Renal Rickets (renal osteodystrophy)

The disorder results from chronic renal failure

(with activity of 1-hydroxylase)

decreased ability to form the active form of the vitamin

(1,25-diOH D3)

Treatment: 1,25-diOH D3 (calcitriol)

Page 45: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

3- Hypoparathyroidism ( PTH)

Deficiency or absence of parathyroid hormone (PTH) causes

hypocalcemia and hyperphosphatemia.

Treatment: any form of vitamin D + PTH

Page 46: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Toxicity of vitamin D

• Vitamin D is the most toxic of all vitamins.

• Vitamin D can be stored in the body and is only slowly metabolized

• High doses (100,000 IU for weeks or months) can cause:

loss of appetite, nausea, thirst and stupor

• Enhanced calcium absorption and bone resorption results in

hypercalcemia, which can lead to deposition of calcium in many

organs, particularly the arteries and kidneys

Page 47: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Vitamin K

Page 48: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Vitamin K

Some forms of vitamin K:

1- in plants as phylloquinone (vitamin K1)

2- in intestinal bacterial floras as menaquinone (vitamin K2)

3- synthetic derivative of vitamin K (menadione )

Page 49: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Function of vitamin K 1- Formation of gamma carboxyglutamate

• 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 clotting factors requires the vitamin K-dependent carboxylation of glutamic acid residues

• This forms a mature clotting factor that contains carboxyglutamate (Gla), which are active clotting factors.

Page 50: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

The action of vitamin K can be inhibited by the following

anticoagulants:

• Dicumarol : natural, available in some plants• Warfaryn: a synthetic analog of vitamin K

Page 51: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Interaction of prothrombin with platelets

• The GLA residues of prothrombin are chelatoers of positively charged calcium ions, because of the negatively charged

carboxylate groups.

• The prothrombin – calcium complex is then able to bind

phospholipids essential for blood clotting on the surface of platelets.

• Attachment to platelets increases the rate at which the proteolytic conversion of prothrombin to thrombin can occur.

Page 52: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K
Page 53: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K
Page 54: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

3- Role of gamma carboxyglutamate residues in other proteins

GLA is also present in other proteins (as osteocalcin of

bone) unrelated to the clotting process.

However, the physiologic role of these proteins and the

function of vitamin K in their synthesis is not yet understood.

Page 55: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Distribution and requirement of vitamin K

I. Sources of vitamin K

• Diet source: cabbage, cauliflower, egg yolk & liver.• bacterial flora in the intestine.

II. Requirement of vitamin K

There is no RDA for vitamin K, but 70 – 140 mg / day is recommended

Page 56: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Clinical indications

1- Vitamin K deficiency

• A true vitamin K deficiency is rare as adequate amounts are produced by intestinal bacteria or obtained from diet.

• If the bacterial population of the intestine is decreased as for example by antibiotics, the amount of endogenously formed vitamin is depressed and can lead to hypoprothrombinaemia in malnourished individual (as in debilitated geriatric patient). This condition may require supplementation with vitamin K to correct the bleeding tendency.

• Second generation cephalosporins antibiotics as cefoperazone, cefamandole and moxalactam cause hypoprothrombinemia, by warfaren-like mechanism.

Consequently, their use in treatment is usually supplemented with vitamin K.

Page 57: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

2- Deficiency of vitamin K in the newborn

• Newborns have sterile intestines and cannot initially synthesize vitamin K.

• As human milk provides only about one fifth of the daily requirement for vitamin K,

• So, it is recommended that all newborns receive a single intramuscular dose of vitamin K as prophylaxis against hemorrhagic

disease

Page 58: Fat Soluble Vitamins Vitamin  A Vitamin  E Vitamin  D Vitamin  K

Toxicity of vitamin K

Prolonged administration of vitamin K can produce hemolytic anemia and jaundice in the infant, due to toxic

effects on the membrane of red blood cells.