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Vitamin A and its clinical applications
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
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
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
15.
16.
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.
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
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
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