A comprehensive representation on Vitamin A and its clinical applications for MBBS , BDS ,Biotechnology ,and B Pharm students for self- studies .

1. Vitamin A and its clinical applications
DR ROHINI C SANE

2. 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

3. 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

4. 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

5. 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

6. Chemistry of Vitamin A

7. Biosynthesis of Vitamin A (Retinol) from Beta Carotene
Beta 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 )

8. Biosynthesis of Vitamin A (Retinol) from Beta Carotene

9. 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

10. Dietary sources of Vitamin A
 Animal sources
 Liver oil
 Milk
 Butter
 Cheese
 Egg yolk
 Fish
 Meat

11. Dietary sources of Vitamin A for vegetarians
Tomato
Carrot
Green yellow vegetables
Mango
Papaya
Sweet potato
Dietary sources of Vitamin A

12. 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

13. Absorption ,Storage ,Transport of Vitamin A
Dietary Esters Of Vitamin A + Carotenes
Cholesterol Esterase
Fatty Acids + FREE Vitamin A (RETINOL)
SMALL INTESTINE LUMEN
----------------------------------------------------------------------------------------------------
Resterification of Vitamin A SMALL INTESTINE CELLS
---------------------------------------------------------------------------------------------------
Chylomicrons RBP (RETINOL BINDING PROTEIN)
RABP ( RETINOL ACID BINDING PROTEIN)
BLOOD CIRCULATION
-----------------------------------------------------------------------------------------------
RETINAL ESTERS RETINAL PALMITATE storage(10mg/1oo g) LIVER
RBP RABP
Tissues (eyes ,skin ,bone ,reproductive organs (target cells)

14. 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

17. 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)

18. 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.

20. Biochemical changes in cone cells for color vision

22. Visual Cascade Involving Bleaching Of Rhodopsin
Rhodopsin
Prelumirhodopsin
Lumirhodopsin
Metarhodopsin I
Metarodopsin II opsin+ All Trans Retinol
Transducin (Inactive)+ GTP  Transducin(Active) + GDP

23. 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

24. Visual Cascade Involving Cyclic Guanosine Monophosphate
Hyper polarization
Excitory response transmitted through neuron network
Visual cortex of brain
Visual perception

25. Visual Cascade Involving Cyclic Guanosine Monophosphate

26. Visual Cascade Involving Cyclic Guanosine Monophosphate
Hyper polarization

27. Interaction of Rhodopsin and Transducin in visual perception

28. 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 )

29. 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

30. Xeropthalmia: Bitot spots
Horny irruptions on skin
Deficiency manifestations of Vitamin A

31. 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

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

33. Deficiency manifestations of Vitamin A
(A) Defective bone & teeth formation
(B) Osteoblastic activity decreased bone formation decreased
(C) Mechanical damage to brain & spinal cord

34. Defective Osteoblastic activity decreased bone formation decreased
Deficiency manifestations of Vitamin A

35. 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