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Vitamin A
1.
2. Vitamin A
Gandham. Rajeev
Department of Biochemistry,
Akash Institute of Medical Sciences
& Research Centre,
Devanahalli, Bangalore,
Karnataka, India.
eMail: gandhamrajeev33@gmail.com
3.
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 âeâ
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 â 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( Waldâs 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
Îľ âamino 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. ⢠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
34. ⢠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
35. ⢠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
36. 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
37. ⢠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
38. ⢠Significance:
⢠The antioxidant properties of beta âcarotene
is partly responsible for its anticancer
activity, protective effect against coronary
heart disease, and prevention of cataract
formation
39. 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 Οg retinol
⢠= 6 Οg beta-carotene
⢠= 12 Οg other carotinoids
⢠Children = 400 â 600 Îźg /day
⢠Men = 750 â 1000 Îźg /day
40. ⢠Women = 750 Οg /day
⢠Pregnancy = 1000 Οg /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
41. ⢠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
42.
43. ⢠The conjunctiva gets keratinized and loses
its normal transparency
⢠Dryness spreads to cornea
⢠It becomes glazy and lusterless due to
keratinization of corneal epithelium
⢠Bitotâs spots:
⢠These are seen as greyish-white triangular
plaques firmly adherent to the conjunctiva in
certain areas
44.
45. ⢠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
46. 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
47. 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
48. ⢠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 Οg/dl
49. References
⢠Harperâs 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