Vitamin A was discovered in 1913 and its chemistry was further elucidated in the 1930s. It plays important roles in vision, growth, cell differentiation, and immune function. Vitamin A is absorbed in the small intestine and transported to the liver bound to retinol binding protein. It is then distributed to tissues as needed. In the eyes, vitamin A is involved in the visual cycle and allows for dark adaptation. Deficiency can lead to night blindness and even blindness. The RDA is met through foods like liver, sweet potatoes, carrots and dairy. Too much vitamin A can be toxic. Recent research suggests it may help treat colds and flu when taken with vitamin D.

1. VITAMINA
Prof. Dr. V.P. Acharya

2. What do we learn???
• How it was found and named?- History
• How it looks and behaves- the chemistry
• What happens to it in our body?- The
metabolism
• What’s its role?- Biochemical functions
• How much is required?- RDA
• How much is too much?- Hypervitaminosis A
• What’s new?- Recent advances

3. General format
Vitamin
(Synonym if
any)
Chemistry Metabolic
functions
Dietary
source
RDA Deficiency
manifestations
Hypervitaminosis Other

4. History
• Greeks- Beef liver raw dipped in honey as a
remedy to nightblindness
• 1913- Mc Collum, Simmonds and Kennedy
isolated vitamin A
• Richard Kuhn- Identified carotene
• 1931- Paul Karrer identified the structure of
Vitamin A1

5. Chemistry
Active form only in animals
Retinoids – Retinol, Retinal & Retinoic
acid; Preformed, found in animal
origin
Carotenoids- α-, β-, γ- carotenes &
Cryptoxanthines, plant origin,
Provitamin
Vitamin A activity of β-carotene is –
1/12 of retinol activity
Vit A1- All trans retinal MC variety

6. Beta- carotene- ideally should yield 2 retinal;
conversion inefficient
Retinal can be converted to retinol but easily reversible.
Retinal → Retinoic acid (Irreversible)

7. The Metabolism

8. Absorption
Beta carotene
↓
Retinal
NADH/ NADPH ↓
Retinol
↓
Absorbed through intestinal mucosal cell along
with other fats and bile salts
↓
Within cell, retinol is re-esterified, incorporated
into chylomicrons and taken to liver
↓
Liver to peripheral tissue by RBP (Retinol binding
protein)
Di-oxygenase
Retinal reductase

9. Mechanism of action of Vitamin A
RBP-Retinol complex goes to extra-hepatic tissues- Retina,
skin, gonads and other tissues
↓
Transport protein on cell surface carries retinol
↓
Retinol oxidized → Retinoic acid
↓
Binds to specific receptor proteins (Retinoic acid receptors
RAR) present in the nucleus
↓
Bind to HRE (Hormone receptor elements) on DNA
↓
Retinoid –specific RNA synthesis

10. Mechanism of action of Vitamin
A

12. Biochemical role of Vitamin A

13. Wald’s Visual cycle
George Wald
NP- 1967

16. The Eye & Phototransduction
Light enters from here.
Photoreceptors face away.
Anterior
Posterior

17. The Eye & Phototransduction
1. Rods out number cones by approximately 100 million to 5
million, in each eye.
2. The most central part of the retina contains only cones.
Cone density decreases with eccentricity, and in the far
periphery, only rods are found.
3. Lumping rods and cones together, photoreceptor density
(overall) decreases with eccentricity. So, vision is less
sharp in the periphery.

18. Photo receptor

19. 1- Photo pigment (rhodopsin)
2- G protein transducin
3-CGMP phospho-diesterase enzyme
Each disk contains….

20. How Nerve conduction works???

21. When light hits a photoreceptive pigment within the
photoreceptor cell
↓
Rhodopsin changes to Metarhodopsin II on photon exposure
↓
Metarhodopsin II activates transducin
↓
Activation of cGMP phosphodiesterase
↓
cGMP→ 5’GMP
↓
↓cGMP
↓
Closes the Na+ gated channels
↓
hyperpolarization of the rod
↓
Ca++ channels closed
↓
stopping the release of neurotransmitters (Glutamate)

22. How to stop this??
Phosphorylation of serine residue of
activated rhodopsin
↓
Inhibitory protein Beta-arrestin
binds
↓
Inactivates rhodopsin
Rhodopsin kinase

23. Dark adaptation
• Bright light
bleaches
rhodopsin
• In Vit A
deficiency
dark
adaptation
time
increases↑

24. Cones for colour vision
• Conopsin
• 3 types of cones- Cyanopsin, iodopsin,
porphyropsin
• Similar mechanism as rods

26. Growth and differentiation
• Regulation of gene expression-- All-trans-
retinoic acid & 9-cis-retinoic acid- act like steroid
hormones
• All-trans retinoic acid binds to RAR & 9-cis-
retinoic acid binds to RXR
• Cell differentiation
• Epithelial maintenance
• Immune cell proliferation
• Matrix protein sulfation - bone growth

27. Vitamin A deficiency leads to
hamper Vitamin D action !!
• RAR & RXR receptors
• Vitamin D binds to RXR receptors
• Vit A deficiency- receptor dimers of Vit.
D is not formed.
• Retinol- reproductive function
• β-Carotene- antioxidants

28. Vitamin A
Dr. V.P.Acharya
Dietary source

29. Daily requirement
• Infants & children- 400-600 μg / day
• Male- 750-1000 μg / day
• Female- 750 μg / day
• Pregnancy- 1000 μg / day
• Lactation- 1200 μg / day

30. Bitot’sspot Keratomalacia
Deficiency manifestation
How deficiency occurs??
• ↓ intake
•Obstructive jaundice
•Cirrhosis of liver
•Severe malnutrition- RBP
synthesis ↓

31. • Nyctalopia/ Night-blindness
• Xerophthalmia
• Bitot’s spots
• Keratomalacia
• Blindness
• Hyperkeratosis / Phrynoderma
• Keratinizing metaplasia of resp epithelium, GIT,
genitourinary tract
• Urinary calculi
• ↑Infections
• Growth retardation- skeletal growth

32. Vitamin A is toxic in excess
• Unbound Vitamin A
causes toxicity
• CNS- pseudotumour
cerebri
• Hepatomegaly
• Hyperlipidaemia
• Hypercalcaemia,
thickening of long bones,
calcinosis
• Drying of skin,
desquamation, alopecia

33. Therapeutic use
• Tretinoin (All trans retinoic acid)- synthetic
preparation
• Retinol- dietary supplement
• Retinoic acid- Dermatology
• Isotretinoin (isomer of retinoic acid)–used
for severe and disfiguring cystic acne but is
teratogenic

35. Vitamin A supplementation
??
• 1970- National Prophylaxis
Programme against
Nutritional Blindness due to
vitamin A deficiency (NPPNB
due to VAD)
• 1lakh IU- 9mth along with
measles vaccine
• 2lakh IU 6 mthly upto 5 years
• Therapeutic dose- 2 lakh unit
at 4 week’s interval twice

36. Vitamin A fortification
Fat
Oil
MilkCereals
Refined
sugars

37. What’s new??
• Can cure cold and flu when supplemented
with Vitamin D

38. Thanks for a patient listening

39. For more ppt on Medical Biochemistry please visit my website
www.vpacharya.com