vitamin a and its clinical applications

Vitamin A and its clinical applications

DR ROHINI C SANE

Classification of vitamins

Classification of vitamins

a) Fat soluble vitamins : Vitamin A, Vitamin D ,Vitamin E ,Vitamin K

b) Water soluble vitamins :Vitamin C (Ascorbic acid ) & B- complex vitamins

Properties of fat soluble vitamins and Vitamin A

Definition of fat soluble vitamins : organic compounds required in

minute amount for maintenance ,growth ,reproduction

Properties of fat soluble vitamins

(1)No structural role

(2)Don't undergo degradation for energy purpose

(3)Not synthesized ---therefore to be supplied in diet

(4)B complex functions as coenzymes

B- COMPLEX VITAMINS

1. Thiamine (Vitamin B1)

2. Riboflavin (Vitamin B2)

3. Pyridoxine (Vitamin B6)

4. Cyanocobalamin (Vitamin B12)

5. Niacin (Nicotinic acid )

6. Pantothenic acid

7. Lipoic acid

8. Biotin

9. Folic acid

10. Para amino benzoic acid

11. Choline

12. Inositol

VITAMIN A

Papyrus – Cured patients with NIGHT BLINDNESS by supplementing (OX liver + honey)

1913 - Hopkin isolated Vitamin A from milk

1913 Baxer Isolated Vitamin A from fish liver oil

❖ Retinoids

a) R - CH2 OH = RETINOL ( VITAMIN A --ALCOHOL )

b) R – CHO = RETINAL (VITAMIN A ALDEHYDE )

c) R- COOH = RETINOIC ACID

Provitamins A (Alpha Beta Gamma carotene are all yellow pigments )

Vitamin A

Chemistry of Vitamin A

Trimethyl Cyclohexenyl Ring (Beta Ionone)+Isoprenoid chain with double bonds

Chemistry of Vitamin A

Biosynthesis of Vitamin A (Retinol) from Beta CaroteneBeta Carotene

O₂ Bile salts Beta Carotene Dioxygenase

Vitamin A Aldehyde (Retinal) CHO

Retinaldehyde Reductase NADPH +H⁺ Reduction

NADP ⁺

RETINOL (VITAMIN A ALCOHOL )CH ₂ OH

Oxidation

Retinoic Acid ( COOH )

Biosynthesis of Vitamin A (Retinol) from Beta Carotene

Properties of Vitamin A

1. Yellow oil

2. Heat stable

3. Oxidation labile (protected by Vitamin E )

4. Alcoholic hydroxyl group forming esters

5. Melting point : 62-65º C

6. Molecular weight of Vitamin A : 286

7. Carr price test :Vitamin A +SbCl3 blue complex(Absorption maximum at 693)

2 (Beta ionone ) OF Beta Carotene 2 Vitamin A

Dietary sources of Vitamin A

Animal sources

Liver oil

Milk

Butter

Cheese

Egg yolk

Fish

Meat

Dietary sources of Vitamin A for vegetarians

Tomato

Carrot

Green yellow vegetables

Mango

Papaya

Sweet potato

Dietary sources of Vitamin A

Recommended Daily Allowance/Requirement of Vitamin A

5000 IU = 1000 Retinol units

1 IU = 0.3 Micrograms Retinol

= 0.344 Micro Retinol Alcohol

= 0.6 Micrograms Beta Carotene

Dietary requirement of vitamin A increases

Pregnancy

Lactating woman

Growing children

Injuries

Wound healing

Absorption ,Storage ,Transport of Vitamin A

Dietary Esters Of Vitamin A + Carotenes

Cholesterol Esterase

Fatty Acids + FREE Vitamin A (RETINOL)

SMALL INTESTINE LUMEN

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Resterification of Vitamin A SMALL INTESTINE CELLS

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Chylomicrons RBP (RETINOL BINDING PROTEIN)

RABP ( RETINOL ACID BINDING PROTEIN)

BLOOD CIRCULATION

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RETINAL ESTERS RETINAL PALMITATE storage(10mg/1oo g) LIVER

RBP RABP

Tissues (eyes ,skin ,bone ,reproductive organs (target cells)

Metabolism of Vitamin A Diet

BETA CAROTENE RETINYL ESTERS

FFA

INTESTINAL CELLS

BETA CAROTENE

RETINAL

RETINOL

FFA

RETINOL ESTERS

RETINA (EYE)

ALL TRANS RETINOL

ALL TRANS RETINAL

VISIUAL CYCLE

LIVER ALL TRANS RETINOL

RETINYL PALMITATE (STORED)

TARGET TISSUE

RETINOL

RETINOIC ACIDS

NUCLEAR RECEPTORS

m RNA

PROTEINS ( CELL DIFFERENTIATION )

RBP& RABP

CHYLOMICRONS

Wald’ s Visual Cycle RHODOPSIN LIGHT (PHOTON)

(11 CIS RETINAL –OPSIN)

INCOMPLETE

DIET

RETINOL OPSIN NERVE IMPULSE

RETINAL ISOMERASE

11 CIS RETINAL ALL TRANS RETINAL

NADH+ H⁺ ALCHOL DEHYDROGENASE NADH + H⁺ALCHOL DEHYDROGENASE

NAD ⁺ NAD ⁺

OXIDATION ISOMERASE REDUCTION

11 CIS RETINOL ALL TRANS RETINOL

(LIVER)

ROLE OFVITAMIN A IN COLOR VISION

Porphyropsin Red

Iodopsin Green

Cyanopsin Blue

Red +Blue Violet

Blue + Yellow Green

Red+ Yellow Orange

Vision in dark rod cells 10

millions

Color vision Cone cells vision in

bright light 5 MILLIONS

BAT MORE ROD CELLS THAN CONE

CELLS can visualize in dark.

Biochemical changes in cone cells for color vision

Visual Cascade Involving Bleaching Of Rhodopsin

Rhodopsin

Prelumirhodopsin

Lumirhodopsin

Metarhodopsin I

Metarodopsin II opsin+ All Trans Retinol

Transducin (Inactive)+ GTP Transducin(Active) + GDP

Visual Cascade Involving Cyclic Guanosine Monophosphate

Transducin (ACTIVE)

Phosphodiesterase (inactive) -------------- Phosphodiesterase (ACTIVE) + INHIBITORY UNIT

3,5 C-GMP + PDH (ACTIVE) 5 -GMP

Light low level of C-GMP close Sodium channels increase in Sodium concentration

Dark high level of C-GMP OPEN Na channels decrease in Sodium concentration

Visual Cascade Involving Cyclic Guanosine Monophosphate

Hyper polarization

Excitory response transmitted through neuron network

Visual cortex of brain

Visual perception

Visual Cascade Involving Cyclic Guanosine Monophosphate

Visual Cascade Involving Cyclic Guanosine Monophosphate

Hyper polarization

Interaction of Rhodopsin and Transducin in visual perception

Biochemical functions of Vitamin A

(1) RETINOL/RETINOIC ACID : REGULATE PROTEIN SYNTHESIS & GROWTH

Vitamin A increases synthesis of

(A) Transferrin

(B) Glycoproteins (smooth cell surface /receptor) containing ester of retinoic acid which function

as carriers of Oligo-saccharrides for synthesis of muco-polysaccharides ground collagenous tissue

( C) Chondratin sulphate

(D) Immunoglobulins

(E) Mevalonate cholesterol steroid synthesis maintainance of reproductive health

(F) BETA CAROTENE VITAMIN A synthesis Antioxidant property executed prevention of

cancer & inflammation

***VITAMIN A DEFICIENCY MEVALONATE diverted to Coenzyme Q synthesis

Vitamin A decreases synthesis of KERATIN of hair /skin (horny surface in vitamin A

deficiency )

Deficiency manifestations of Vitamin A

(A) Night Blindness (Nyctalopia): dark adaptation time increased in initial phase &leads to

blindness in untreated patients

(B)Xeropthalmia:

I. dryness of conjunctiva & cornea

II. keratinization of epithelial cells

III. white triangular plaques (Bitot spots)

( C) Keratomalacia :persistent Xeropthalmia corneal ulceration destruction of cornea blindness

( D) Growth retardation :due to decreased glycoprotein and mucopolysaccharide synthesis

Xeropthalmia: Bitot spots

Horny irruptions on skin

Deficiency manifestations of Vitamin A

DEFICIENCY MANIFESTATION OF VITAMIN A

( Defective reproductive growth )

DEFICIENT MALES DEFICIENT FEMALES

decreased sperm formation repeated abortions

NO CONCEPTION

( consequences of Keratinization in epithelial cells )

Defective reproductive growth

rough & dry skin

urinary stones (Calculi )

defective absorption in GIT

Lachrymal gland becomes DRY Xerophthalmic changes observed

Increased susceptibility to respiratory tract infections

Deficiency manifestations of Vitamin A: defective epithelium and that leads to organ dysfunctions

Deficiency manifestations of Vitamin A

(A) Defective bone & teeth formation

(B) Osteoblastic activity decreased bone formation decreased

(C) Mechanical damage to brain & spinal cord

Defective Osteoblastic activity decreased bone formation decreased

Deficiency manifestations of Vitamin A

HYPER VITAMINOSIS A

Excessive consumption of Vitamin A retinol binding capacity of retinol binding exceeds toxicity symptoms observed

Mechanism high concentration of retinol synthesis of lysosomal enzymes destructive action of hydrolases on cell membrane

Normal serum Vitamin A levels :20-50 micrograms /dl

Signs and symptoms of Hypervitoaminois

a) Dermatitis

b) Raised intra cranial pressure

c) Enlargement of liver

d) Skeletal decalcification

e) Tenderness of bones

f) Loss of weight

g) Loss of hair

h) Joint pain

❖ Ingestion of high doses of carotene not toxic decreased incidences of heart attacks, skin &lung cancers