Vitamin A & DVitamin A & D

DR SAKINA ,MBBS,M.D SENIOR LECTURER ,MSU

1.Definition2.Structure of Vitamin3.Absorption and Transport4.Biochemical Function 5.Daily requiremant(RDA)6.Dietary Sources7.Diseases related to deficiency

OBJECTIVES

Vitamin classificationName(Letter) RDIRetinol (A) 5000 IU

Calciferol (D) 400 IU

Tocopherol (E) 30 IU

Phylloquinone (K) 70 g

Fat-soluble Vitamins

• Absorbed with dietary fat in small intestine• 40-90% absorption efficiency• Absorption typically regulated by need

– need absorption• Transported away from small intestine in chylomicra

via blood and lymph (depending on size)• They are not easily excreted through urine.• Substantial amounts are stored in liver and fat tissue.• Therefore, toxicity is possible.

Vitamin A-TypesAll compounds with vitamin A activity are called RETINOIDS

Three different compounds with vitamin A activity are Retinol,retinal,retinoic acid β- CAROTEIN IS PROVITAMIN PRESENT IN PLANT TISSUE

Vitamin ACompounds with 20-carbon structure.

Contain a methyl substituted cyclohexenyl ring (-ionone ring),

and an isoprenoid side chain with either a hydroxyl group, and aldehyde group, a carboxylic acid group, or an ester group (retinyl ester) at the terminal C15.

All-trans-retinal 11-cis-retinal

Retinol Retinoic AcidCan’t be reduced to retinol or retinal in the body.

Vitamin A1. Active vitamin A- Preformed vitamin A can be obtained

directly from foods that are substantial in vitamin A

• The active form of vitamin is retinol, an alcohol which can be converted to other forms (e.g. vitamin A esters)

2. Provitamin A- provitamins, substances that are transformed into vitamins in the body

• Beta-carotene is the most abundant and widespread provitamin A.• Beta-carotene comes from a group of compounds called the

"carotenoids .• One need to eat approximately six times as much beta-carotene to get

the same amount of vitamin A as in retinol.

• Carotenoids are not toxic even at high doses for long times.

Vitamin A: Sources

- Micelle formation- -carotene is cleaved in the lumen of

the intestine by -carotene dioxygenase to yield retinal.

- Retinal is reduced to retinol by retinal reductase, an NADPH requiring enzyme within the intestines.

- The absorption is along with other fats & require bile salts

- Within the mucosal cell retinol is re-esterified with FA,incorporated into chylomicrons & transported to liver & stored as retinol palmitate

Vitamin A: Absorption and transport

Transpot from liver to tissueThe vitamin A from the liver is transported to peripheral tissue as Trans

retinal by RBP(retinol binding protein)

Uptake by tissueRetinol-RBP complex binds to specific receptor(Retina,skin,or gonads ) ,inside

the cytoplasm vitamin binds to CRBP(Cellular retinoic acid binding protein) and finally to HRE(Hormone responsive element) thus genes are activated

Vitamin A: Absorption and transport(CONT…)

Vitamin A: Biological functions• Role in vision. Vitamin A (retinal) is an essential precursor for

formation of the visual pigment, rhodopsin, in the retina of the eye. Retinal plays an important role in vision, especially night vision. Lowers cataract incidence.

• Role in growth. Helps regulate cell development, cell differentiation and cell division.

• Role in Bone and teeth formation. Promotes the proper growth of bones and teeth. Bone cells (osteoblasts and osteoclasts) depend on vitamin A for their normal functioning.– Is important in the formation and maintenance of healthy hair, skin and

mucous membranes. • Role in reproduction. Vitamin A holds an important place in sexual

reproduction. Adequate levels of vitamin A are needed for normal sperm production. The female reproductive cycle requires sufficient amounts of vitamin A.

• Boosts the body's immune system helping to increase body resistance to infectious diseases.

• Retina posses two types of photosensitive cells • Rods –concerened with perception of dim light

vision,Rhodopsin present in rods is made up of 11-Cis Retinal + Opsin

• Cones –concerned with bright light and color vision,contain photosensitive protein Conopsin(photopsin)

• Cones are of three types,characterized by different conopsin

• a)maximally sensitive to blue (cyanopsin)• b)maximally sensitive to green ( iodopsin)• c)maximally sensitive to red (porphyropsin)

RODS & CONES

Role of Vitamin A in Vision(Wald’s visual cycle)

1. Rhodopsin is a conjugated protein with 11-cis retinal+opsin2. When the rhodopsin is exposed to light it is bleached releasing the

11-cis-retinal from opsin. 3. Isomerization of the cis-isomer of retinal to all-trans-retinal,

causes conformational changes in rhodopsin,4. Hyperpolarization of the retinal rod cell, and extremely rapid

transmission of electrical activity to the brain via the optic nerve5. Trans-retinal is isomerized to cis-retinal in the dark, which

associates with opsin to regenerate rhodopsin.

Visual Pigment

All trans retinol = main circulating

form of Vit A

• The single photon can excite the Rod cell• The photon produces immediate conformational

change• The unstable intermediates produced are

• Children-400-600 micrograms/day• Men-700-1000 micrograms/day• Women-750 micrograms/day• Pregnancy-1000 micrograms/day• One international unit =0.3microgram of

retinol

Dietary requirement(RDA)-Vitamin A

Problems associated with Vitamin A

Vit A excess• Hypervitaminosis A in humans

– Symptoms include dry, pruritic skin with excessive itching and increase in intracranial pressure.

– is becoming an increasing problem in Western countries because of self-medication and overprescription.

BLINDNESSKERATOMALACIA

When vitamin A goes abnormal

BITOT SPOTSHYPERKERATOSIS

When vitamin A goes abnormal

• 1.Dark adaptation test - increased in vit A deficiency

• 2.RBP(Retinol binding protein)-level in serum is decreased

• Serum vitamin A is decreased • Normal Blood Level of Vitamin A 25-50 microgram/dl

Assesment of Deficiency-Vitamin A

Vitamin A: Uses Retinol and its precursors are used as dietary supplements to prevent

deficiency symptoms.

Retinoic acid is used in dermatology to cure acne and psoriasis:1. Mild acne (Darier’s disease) and aging

Topical application of tretinoin (all-trans retinoic acid), along with benzoyl peroxide and antibiotics.

2. severe recalcitrant cystic acne Oral consumption of isotretinoin (13-cis retinoic acid). This drug is teratogenic. Should not be prescribed during pregnancy. It may lead to hyperlipidemia and increased LDL/HDL ratio (increased chance of heart disease) in long term.

Vitamin D

Vitamin D: Types and Sources• For humans, the two most important forms of vitamin

D are: – vitamin D2– vitamin D3.

• Vitamin D2 (ergocalciferol) is derived from plants and irradiated yeast and fungi.

• Vitamin D3 is synthesized in the body when skin is exposed to sunlight– Cholesterol + sunshine = Vitamin D3– “sunshine vitamin” – UV-B rays (5-10 minutes arms and legs,

mid-day sun). Vitamin D3 can be obtained from foods like milk,

fortified cereals, tuna, salmon and fish oils.

Diet

Sunlight

Ergosterol(in plants)

Vitamin D2(Ergocalciferol)

7-Dehydrocholesterol

Vitamin D3Cholecalciferol)

Sunlight

Vitamin D-

Secosterol(CIS) Cholecalciferol(D3)(Trans)

Activation of Vitamin D• Vitamin D2 and vitamin D3 are

biologically inactive but can have equal biological activity:

• Both can be converted first to calcidiol in the liver and then to calcitriol, also known as 1,25-dihydroxycholecalciferol, in the kidneys.

• Calcitriol, which is the most active form of vitamin D3, is then transported via a carrier protein to the various sites in the body where it is needed.

Calcitriol is also called 1,25-dihydroxy vitamin D3, or (1,25-(OH)2D3.

Activation of Vitamin D

1,25-dihydroxyvitamin D3

25-hydroxyvitamin D3In the liver cholecalciferol is hydroxylated at the 25 position by a specific D3-25-hydroxylase generating 25-hydroxy-D3 [25-(OH)D3] which is the major circulating form of vitamin D.

Conversion of 25-(OH)D3 to its biologically active form, calcitriol, occurs through the activity of a specific D3-1-hydroxylase present in the proximal convoluted tubules of the kidneys, and in bone and placenta. Cytochrome P450, O2 and NADPH are needed.

Functions of vitamin D• Vitamin D regulates the calcium and phosphorus levels in

the blood by promoting their absorption from food in the intestines, and by promoting re-absorption of calcium in the kidneys.

• It increases the availability of calcium binding protein -CALBINDIN

• It promotes bone formation and mineralization and is essential in the development of an intact and strong skeleton.

• It inhibits parathyroid hormone secretion from the parathyroid gland.

• Vitamin D affects the immune system by promoting immunosupression, phagocytosis, and anti-tumor activity.

Vitamin D: Hormone for Calcium and Phosphate regulation

• Calcium is vital for nerve cell transmissions and muscle fiber contractions.

• Calcitriol functions in contrast with parathyroid hormone (PTH) and calcitonin to regulate serum calcium and phosphorous levels by:

1. Increasing dietary calcium absorption from the small intestine.2. Decreasing the urinary calcium excretion (increasing renal

reabsorption).3. Stimulating resorption of calcium from bone

• Instrumental in the growth, hardening and repair of bones. • Too much vitamin D, however, can increase calcium losses from bone

• Vitamin D is essential for normal insulin secretion by the pancreas and therefore control of blood sugar levels.

Effects of PTH and Vit D3Effects of PTH and Vit D3

Effects of PTH and Vit D3

When vitamin D goes abnormal• Too little leads to Vit D deficiency:

– Rickets (bone deformities in children)– Osteoporosis– Osteomalacia (weak bones)– Demineralization of bones

• Too much (5 times the RDA, chronically): It is most toxic of the vitamins.– Nausea, thirst, loss of appetite, stupor– Hypercalcemia: calcium gets deposited in soft

tissues, arteries and kidneys.

Diseases caused by deficiency• Vitamin D malnutrition may also be linked to an increased

susceptibility to several chronic diseases such as – High blood pressure – tuberculosis – cancer – periodontal disease – multiple sclerosis – chronic pain – depression – schizophrenia– several autoimmune diseases

• The American Pediatric Associations advises vitamin D supplementation of 200 IU/day (5μg/d) from birth onwards.

• Liquid "drops" of vitamin D for infants.

RICKETTSOSTEOMALACIA / RICKETS

Diseases caused by deficiency

• Children- 10micrograms(400 IU)/day• Men-5-10 micrograms/day• Women- micrograms/day• Pregnancy,lactation -10 micrograms/day• Above the age of 60 -600IU/day

Dietary requirement(RDA)-Vitamin D

Specimen-serum Vitamin D 25(OH)D-----10-65 ng/ml Vitamin D1, 25(OH)D-15-60 pg/ml

Reference intervals and values -Vitamin D

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