This document provides information on vitamin A, including its chemical forms and functions. Key points: - Vitamin A exists in retinol, retinal, and retinoic acid forms which are fat-soluble and important for vision, cell growth, and immune function. - The visual cycle involves rhodopsin (retinal bound to opsin) converting light to nerve signals in the retina. - Vitamin A supports epithelial cell integrity, immune function, reproduction, and is important for preventing deficiencies like night blindness. - Dietary sources include liver, dairy, eggs, yellow/green vegetables and fruits like carrots which contain provitamin A carotenoids.

1. Vitamin A
Prepared By -; Roll no- 81 to 84

2. - Vitamin-A
-Vitamin-D
-Vitamin-E
-Vitamin-K
Vitamin-C
-Thiamine (B1)
-Riboflavin (B2)
-Niacin (B3)
-Pyridoxine (B6)
-Biotin (B7)
-Pantothenic Acid (B5)
-Folic Acid (B9)
-Vitamin B12
(Cyanocobalamin

3. Vitamin A
• Vitamin A is a fat soluble Vitamin.
• Present only in foods of animal origin
• Its provitamins carotenes are found
in plants
• Chemistry:
• Retinol, retinal and retinoic acid are
termed as vitamers of Vitamin A

4. • It is a primary alcohol containing β-ionone
ring
• The side chain has two isoprenoid units,
four double bonds and one hydroxyl group
• Retinols present in animal tissues as
retinyl ester with long chain fatty acids
CH3
CH3
CH2OH
CH3
β-Ionone
CH3 CH3
Retinol

5. Retinal (Vitamin A
aldehyde)
• This is an aldehyde form obtained by
the oxidation of retinol.
• Retinal and retinol are interconvertible
CH3
CH3
CHO
CH3
β-Ionone
CH3 CH3
Retinal

6. Retinoic acid (vitamin A
acid)
• This is produced by the oxidation of retinal
• Retinoic acid cannot give rise to the
formation of retinal or retinol
CH3
CH3
COOH
CH3
β-Ionone
CH3 CH3

7. • This is present in plant foods
• It is cleaved in the intestine to produce two
moles of retinal; but it may produce only
one in biological system
CH3
CH3
β -
Carotene
CH3
β-Ionone
CH3 CH3 CH3 CH3 CH3 CH3
H3C

8. • All the compounds with vitamin A activity
are referred as retinoids
• They are poly-isoprenoid compounds
having beta-ionone ring system
• The retinal may be reduced to retinol
by retinal reductase and it is
reversible
• Retinal is oxidized to retinoic acid ,
which cannot be converted to the other
forms
Retinol (alcohol) Retinal (aldehyde)
Retinoic acid
Reductase
NAD+ NADH +
H+

9. Absorption of vitamin A
• Dietary retinyl esters are hydrolyzed by
pancreatic or intestinal brush border
hydrolases, releasing retinol and free
fatty acids
• β- Carotene is cleaved by di-oxygenase
of intestinal cells to release 2 moles of
retinal
• Retinal is reduced to retinol by an NADH or
NADPH dependent retinal reductase
present in intestinal mucosa

10. • In the intestinal mucosal cells, retinol is
reesterified to long chain fatty acids,
incorporated into chylomicrons and
transferred to the lymph
• Intestine is the major site of absorption
• Absorption is along with other fats and
requires bile salts
• In biliary tract obstruction and steatorrhoea,
vitamin A absorption is reduced
• The retinol esters of chylomicrons are taken
up by the liver and stored (As retinol
palmitate)

11. • Transport from liver to tissues:
• Vitamin A is released from the liver as retinol
• Zn is essential for retinol metabolism
• Retinol is transported in the circulation by the
retinol binding protein(RBP) in association
with pre-albumin
• One molecule of RBP binds one molecule
of retinol
• The retinol-RBP complex binds to specific
receptors on the cell membrane of
peripheral tissue and enters the cells

12. • Many cells of target tissues contain a
cellular retinol-binding protein (CRBP)
that carries retinol to the nucleus and
binds to the chromatin (DNA)
• Retinol exerts its function in a manner to
that of a steroid hormone
• Retinoic acid is mainly transported in
the blood by binding to albumin
• Small amounts of retinoic acid in the blood
is also transported in combination with
apo- retinol binding protein

13. Intestinal cell
β-Carotene
Retinal
Retinol
Retinyl esters
Chylomicrons
All-trans-retinol
Retinyl palmitate (stored)
Retinol
Retinol-RBP
Target cell
Retinol
Retinoic acid
Nuclear receptor
m-RNA
Specific proteins
Cell differentiation
Retina
All-
transretinol
All-trans
retinal
Visual Cycle
Diet
β-carotene Retinylesters
FF
A
Retinol

14. Biochemical functions
• Rods and cones
• The retina of the eye possesses two types
of cells – rods and cones
• The human eye has about 10 million rods and
5 million cones
• The rods are in the periphery while cones are
at the centre of retina
• Rods are involved in dim light vision
• Cones are responsible for bright light
and colour vision

15. Vitamin A and Vision( Wald’s visual cycle)
• Rhodopsin (mol.wt.35,000) is a
conjugated protein present in rods
• It contains 11-cis-retinal and the
protein opsin
• When light falls on retina, 11-cis-retinal
is isomerised to all-trans-retinal
• This leads to a conformational change
in opsin

16. • Responsible for the generation of nerve
impulse
• The all-trans retinal is isomerized to 11-cis-
retinal by retinal isomerase (retinal
epithelium)
• This combines with opsin to regenerate
rhodopsin and complete the visual
cycle
• Most of the all-trans retinal is transported
to liver and converted to all-trans retinol

17. • The all-trans retinol is undergoes
isomerization to 11-cis retinol which is
oxidized to 11-cis retinal to participate in
the visual cycle

18. Rhodopsin
(11-cis-retinal+opsin)
All-trans-retinal
All-trans-retinol
NAD+
NADH +
H+
ADH
(liver)
11-cis-retinol
11-cis-retinal
NAD
NADH +
H+ ADH(liver)
Isomerase (liver)
Opsin
Retinal isomerase
Wald’s visual cycle
Light

19. Dark adaptation
mechanism:
• When a person shifts from a bright light to a
dim light, rhodopsin stores are depleted
and vision is impaired
• After few minutes rhodopsin is
resynthesized and vision is
improved
• Called as dark adaptation and is
increased in Vitamin-A deficiency

20. Bleaching of rhodopsin
• When exposed to light, the color of rhodopsin
changes from red to yellow by a process
known as bleaching
• Bleaching occurs in a few milliseconds and
many unstable intermediates are formed
during this process
• Rhodopsin Prelumirhodopsin Lumirhodopsin
• All-trans-retinal +
Opsin
metarhodopsin II Metarhodopsin I

21. Visual cascade and
cGMP
• When light strikes the retina, a number of
biochemical changes leading to membrane
hyperpolarization occur resulting in
genesis of nerve impulse
• When a photon (from light) is absorbed
by rhodopsin, metarhodopsin II is
produced
• The protein Transducin is activated
by metarhodopsin II

22. • Involves the exchange of GTP for GDP
on inactive transducin
• The activated transducin activates
cyclic GMP phosphodiesterase
• This enzyme degrades cGMP in rod cells
• A rapid decrease in cGMP closes Na+
channels in the membrane of the rod
cells
• This results in hyperpolarization which is an
excitatory response transmitted through
the neuron network to the visual cortex of

23. • Cones are responsible for vision in
bright light as well as color vision
• They contain the photosensitive
protein, conopsin
• There are three types of cones, each is
characterized by a different conopsin, that
is maximally sensitive to either - blue
(cyanopsin), green (iodopsin), red
(porphyropsin)

24. • In cones, 11-cis-retinal is
the chromoprotein
• Reduction in number of cones or
cone proteins, will lead to color
blindness
• One eye contains about 6 million
cones

25. Other biochemical functions of vitamin
A
• Retinol and retinoic acid function like
steroid hormones
• They regulate protein synthesis and
involved in cell growth and differentiation
• Vitamin A is essential to healthy
epithelial tissue
• Vitamin A is considered to be essential
for maintenance of proper immune
system

26. • Active form: The active form of vitamin A
which is involved in reproduction is
retinol
• Mechanism: retinol binds to
specific intracellular receptor
• Retinol receptor complex binds to DNA
and regulates the expression of genes
required for reproductive function

27. • Active form: The active form of vitamin A
involved in growth and differentiation is
retinoic acid
• Mechanism: retinoic acid (present as either all
trans-retinoic acid or 9 cis-retinoic acid) binds
to specific cellular retinoic acid binding
protein (receptor)
• Retinoic acid receptor complex binds to DNA
and regulate the expression of genes
required for growth and differentiation

28. • In cancer treatment all-trans retinoic acid
has been shown to cause differentiation of
tumors, and has a potential for the
treatment of cancer
• All-trans retinoic acid also induces
apoptosis (programmed cell death)
of cancer cells

29. Role in maintenance of epithelial
integrity and glycoprotein
synthesis
• Active form: Retinol is involved in the
maintenance of epithelial integrity
and glycoprotein synthesis
• Retinol prevents the excess keratin
synthesis
• Retinyl phosphate formed from retinol
is required for glycoprotein synthesis
• Glycosyl retinyl phosphate acts as donor of
carbohydrates for synthesis of glyco-
proteins and GAGs

30. • Collagen breakdown: Retinoic acid
inhibits the enzyme collagenase and thus
prevents the breakdown of collagen
• Role of β- Carotene as an antioxidant:
• The antioxidant effect of beta-carotene
is due to the stabilization of peroxide
free radicals within the conjugated alkyl
structure of beta-carotene

31. • Significance:
• The antioxidant properties of beta –
carotene is partly responsible for its
anticancer activity, protective effect against
coronary heart disease, and prevention of
cataract formation

32. Recommended dietary allowance(RDA)
• The daily requirement of vitamin A is
expressed as retinol equivalents (RE)
rather than International Units (IU)
• 1 retinol equivalent = 1 μg retinol
•
•
Children
Men
Women
Pregnancy
= 400 – 600 μg /day
= 750 – 1000 μg /day
= 750 μg /day
= 1000 μg /day or 1 mg/day

33. • Dietary sources of vitamin A:
• Animal sources: Include milk, butter,
cream, cheese, egg yolk and liver
• Fish liver oils ( cod liver oil and shark liver oil
) are very rich sources of the vitamin A
• Vegetable sources contain yellow
pigment beta-carotene

34. • Yellow and dark green vegetables and
fruits are good sources of carotenes e.g.
carrots, spinach, pumpkins, mango,
papaya etc.
+ Deficiency of vitamin A:
• Visual acuity is diminished in dim
light (nyctalopia or night blindness)
• The dark adaptation time is increased
• Xerophthalmia
• The conjunctiva becomes dry, thick
and wrinkled

36. • The conjunctiva gets keratinized and
loses its normal transparency
• Dryness spreads to cornea
• It becomes glazy and lusterless due
to keratinization of corneal
epithelium
• Bitot’s spots:
• These are seen as greyish-white triangular
plaques firmly adherent to the conjunctiva
in certain areas

38. • Keratomalacia:
• When the xerophthalmia persists for a long
time, it progress to keratomalacia
(softening of cornea)
• There is degeneration of corneal
epithelium which may get vascularised
• Later, corneal opacities develop
• Bacterial infection leads to corneal
ulceration, perforation of cornea and
total blindness

40. Other deficiency
manifestations
• Effect on growth:
• Vitamin A deficiency results in growth
retardation due to impairment in
skeletal formation
• On reproduction:
• The reproductive system is
adversely affected in vitamin A
deficiency
• Degeneration of germinal epithelium
leads to sterility in males

41. Effect on skin and epithelial cells:
• The skin becomes rough and dry
• Keratinization of epithelial cells of GIT,
urinary tract and respiratory tract
• Vitamin A deficiency is associated
with formation of urinary stones
• Hypervitaminosis:
• Excessive consumption of vitamin A leads
to toxicity

42. • Symptoms: Dermatitis (drying and
redness of skin), enlargement of liver,
skeletal decalcification, tenderness of
long bones, loss of weight, irritability,
loss of hair, joint pains
• Normal range: 20 -50 μg/dl