Vitamin A is a fat-soluble vitamin that exists in multiple forms including retinol, retinal, and retinoic acid. It plays an essential role in vision, cell growth and differentiation. Vitamin A is absorbed in the small intestine and transported to the liver where it is stored. A deficiency can impair vision and cause dry eyes and corneal ulceration or blindness in severe cases. The recommended daily intake is 400-1000 μg depending on age, sex and life stage.
2. Vitamin A
Gandham. Rajeev
Department of Biochemistry,
Akash Institute of Medical Sciences
& Research Centre,
Devanahalli, Bangalore,
Karnataka, India.
eMail: gandhamrajeev33@gmail.com
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4.
5. VITAMINS
Vitamins may be regarded as Organic
compounds required in the diet in small
amounts to perform specific biological
functions for normal maintenance of optimum
growth and health of the organisms
Hopkins coined the term Accessory factors to
the unknown and essential nutrients present
in the natural foods
6. • Funk (1913) is isolated an active principle (an
amine) from rice polishings and , later yeast,
which could cure beri-beri in pigeons.
• He coined the term Vitamine
• Vital + Amine
• Earlier identified ones had amino groups.
• It was later realized that only few of them are
Amines.
• The term Vitamin-continued without the final
letter ‘e’
7. Classification
• All vitamins are broadly divided into two groups
according to solubility.
• Fat-soluble
• Vitamin-A
• Vitamin-D
• Vitamin-E
• Vitamin-K
10. 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
11. • 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
CH3CH3
CH2OH
CH3
β-Ionone
CH3 CH3
Retinol
12. Retinal (Vitamin A aldehyde)
• This is an aldehyde form obtained by the oxidation
of retinol.
• Retinal and retinol are interconvertible
CH3CH3
CHO
CH3
β-Ionone
CH3 CH3
Retinal
13. 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
CH3CH3
COOH
CH3
β-Ionone
CH3 CH3
14. • 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
CH3CH3
β - CaroteneCH3
β-Ionone
CH3 CH3 CH3 CH3 CH3 CH3
H3C
15. • 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+
16. 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
17. • 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)
18. • 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
19. • 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
21. 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
• The number of rods is more in cats, mice and owls
22. 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
• The aldehyde group (of retinal) is linked to
ε –amino group of lysine(of opsin)
• When light falls on retina, 11-cis-retinal is
isomerised to all-trans-retinal
• This leads to a conformational change in opsin
23. • 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 by alcohol
dehydrogenase
24. • The all-trans retinol is undergoes isomerization
to 11-cis retinol which is oxidized to 11-cis retinal
to participate in the visual cycle
26. 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
27. 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
28. 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
29. • 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 brain
30. • 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)
31. • 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
32. 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
33. 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
• = 6 μg beta-carotene
• = 12 μg other carotinoids
• Children = 400 – 600 μg /day
• Men = 750 – 1000 μg /day
34. • Women = 750 μg /day
• Pregnancy = 1000 μg /day or 1 mg/day
• 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
35. • 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
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37. • 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.
39. • 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. References
• Harper’s Biochemistry 25th Edition.
• Fundamentals of Clinical Chemistry by Tietz.
• Text Book of Medical Biochemistry-A R Aroor.
• Text Book of Biochemistry-DM Vasudevan
• Text Book of Biochemistry-MN Chatterjea
• Text Book of Biochemistry-Dr.U.Satyanarana