This document summarizes key information about vitamins A. It discusses that vitamin A has two groups that provide activity - preformed vitamin A found in animal foods and carotenoids from plants. Deficiency can cause blindness, while excess intake can lead to hypervitaminosis A with symptoms like increased intracranial pressure. Vitamin A plays important roles in vision, reproduction, growth, immune function and epithelial tissue maintenance.

1. VITAMINS
Dr. Muhammad Sarfraz
M.B.B.S., M.Phil.(Pharmacology)
Senior Demonstrator
Quaid-e-Azam Medical College
Bwp.
1

2. Vitamin A
2

3. vitamin A
Beta-ionone ring
attached to
isoprenoid chain
Both structural features are
essential for vitamin activity
Called a
Retinyl Group 3

4. 4

5. 5

6. Vitamin A
• Two Groups of Compounds
Have Vitamin A Activity
6

7. 1st Group
Pre-formed Vitamin A
Only In Foods Of
Animal Origin
Retinol
7

8. Retinoids
• RETINOIDS comprise
of
• Retinol
• Retinaldehyde
• Retinoic Acid
8

9. © 2008 Thomson - Wadsworth

10. 10

11. 11

12. 12

13. 13

14. Vitamin A
2nd group
• CAROTENOIDS, found in
plants, are composed of
β-carotenes
PRECURSORS OF VITAMIN A
Cleaved To Yield
Retinaldehyde
14

15. 15

16. 16

17. Vitamin A
β-carotenes
Cleaved In The
Intestinal Mucosa
By
Carotene Dioxygenase
17

18. Vitamin A
Conversion of carotenes is
inefficient
One 6th-12th of retinol’s
activity
Yielding
Retinaldehyde
18

19. 19

20. PRINCIPAL SITE OF
Carotene Dioxygenase
ATTACK
IS THE CENTRAL BOND OF
β-CAROTENE
20

21. 21

22. 22

23. Vitamin A
Retinal reduced To Retinol
Esterified with long chain
fatty acids
23

24. Vitamin A
Secreted as components of
Chylomicrons in lymphatics
Together With Esters
Formed From Dietary
Retinol
24

25. 25

26. 26

27. 27

28. 28

29. 29

30. 30

31. 31

32. 32

33. Unit of activity
International units (I.U.)
• 0.3 µg of retinol = 1 I.U.
• Daily requirement
• Adult Male And Female
• 3000 I.U. /day
33

34. Unit of activity
International units (I.U.)
• Recommended Allowance
• 5000 I.U./ day
• Higher In
Growing Children, Pregnant Women
, Lactating Mothers
and
HEPATIC DISEASE
34

35. • Absorption
Small intestine
(vit.A and carotene
precursors)
35

36. • Tocopherols (Vit.E) And
Other Antioxidants
Protect
Against Oxidation And
Destruction In Small
Intestine
36

37. • DIETARY VIT.A ….ester
form …hydrolysis…by
..cholesterol esterase---
• Free retinol ….Absorbed ---
-Re Esterification In
Intest.Epithelial Cells
37

38. 38

39. • Storage
• In Liver As Retinyl Ester……
Retinyl Palmitate…95% Of Stored
Vit.A
• RELEASED WHEN REQUIRED
• 10-20 mg of vit.A /100 gm of liver.
39

40. 40

42. • Transport
• In blood….retinol binding
protein…RBP
• Retinoic Acid Binding
Protein..RABP
• Cellular.. RBP
42

43. RETINA
TARGET TISSUES
ABSORPTION
TRANSPORT
AND
STORAGE

44. ABSORPTION
TRANSPORT
AND
STORAGE

45. MECHANISM OF ACTION OF VITAMIN
“A”
• Retinoic acid …. Binds with
high affinity to specific proteins
in the nucleus of target tissues
• Activated retinoic acid-receptor
complex interacts with nuclear
chromatin…..
45

46. MECHANISM OF ACTION OF VITAMIN
“A”
• Stimulation of retinoid-
specific RNA synthesis
• Mediation of physiologic
functions
46

47. Role of vitamin A
•VISION (RETINAL)
•REPRODUCTION
• GROWTH AND CELL
DIFFERENTIATION
47

48. Role of vitamin A
•MAINTENANCE OF
EPITHELIAL TISSUES
• CONTROL OF KERATIN
PRODUCTION
48

49. Role of vitamin A
• RETINOIC ACID
Mediates Most Of The Actions
Except Vision
49

50. Role of vitamin A
• Retinoid X receotors form
dimers with vitamin D and
thyroid hormone receptors
• So deficiency of vitamin A
impairs vitamin D and thyroid
hormone function
50

51. vision
51

52. Functions of vit.A
In The RETINA
RETINALDEHYDE
Functions As The
Prosthetic Group
Of The
Light-sensitive
Proteins
Opsin 52

53. Functions of vit.A
RHODOPSIN
Visual Purple
In Rods
And
IODOPSIN
In Cones
53

54. Functions of vit.A
• Cones
specialized for color and
detailed vision in bright
light
• Rods
Specialized for vision in
dim light …. Night vision54

55. 55

56. Functions of vit.A
• In the pigment epithelium
of the retina
• ALL-TRANS-RETINOL
• Isomerized to
11-cis-RETINOL
• Oxidized to
• 11-cis-RETINALDEHYDE
56

57. 57

58. Functions of vit.A
• The aldehyde group of retinal
Reacts With Amino group of
Lysine Residue in opsin,
forming the holo-protein
RHODOPSIN.
• Rhodopsin has light absorbing
property
• Even dim light can break
rhodopsin 58

59. 59

60. Functions of vit.A
• When light falls on rhodopsin
• It splits into opsin and all
trans retinal in series of
events
60

61. 61

62. 62

64. • the absorption of light by
rhodopsin
•  isomerization of the
retinaldehyde from 11-cis to
all-trans, and a conformational
change in opsin.
• release of retinaldehyde
from the protein
64

65. • the initiation of a nerve
impulse.
•  series of conformational
changes
•  formation of metarhodopsin
II,
 initiates a guanine nucleotide
amplification cascade and
then a nerve impulse.
65

66. • Final Step Is Hydrolysis of
RHODOPSIN
• Release ALL-TRANS-
RETINALDEHYDE And OPSIN
• Key To Initiation Of The Visual
Cycle Is The Availability Of 11-
cis-Retinaldehyde, And Hence
Vitamin A. 66

68. • In Deficiency,
Both The Time Taken To Adapt
To Darkness And The Ability
To See In Poor Light Are
Impaired
68

69. Impaired dark
adaptation time
Decreased vitamin
A in plasma
Decreased
RBP in plasma
Normal
plasma
vitamin A
20 to 80
µg/100ml

70. 70

71. 71

72. Vitamin A Deficiency Is The Most Important
Preventable Cause Of Blindness
Earliest Sign Of Deficiency
Loss Of Sensitivity To
Green
Light
followed by
 Impairment To Adapt To Dim
Light
followed by
 NIGHT BLINDNESS 72

73. Vitamin A Deficiency Is The Most Important
Preventable Cause Of Blindness
Keratinization
Of Cornea
Leading To
Permanent
Blindness 73

74. Role in the Regulation of Gene Expression and
Tissue Differentiation
• Control Of Cell
Differentiation And
Turnover
• Regulate
Growth,Development, And
Tissue Differentiation
74

75. Role in the Regulation of Gene Expression and
Tissue Differentiation
• Retinol
Essential for normal
reproduction
Supporting spermatogenesis
in the male
preventing fetal resorption
in the female 75

76. Role in the Regulation of Gene Expression and
Tissue Differentiation
Control The Expression
Of The
Gene For Keratin
In Most Epithelial
Tissues Of The Body
76

77. Role in the Regulation of Gene Expression and
Tissue Differentiation
Retinoic Acid
Binds To
Nuclear Receptors
That Bind To Response
Elements Of DNA And
Regulate The Transcription
Of Specific Genes 77

78. 78

81. Vitamin A deficiency is the most
important preventable cause of
blindness
• More prolonged deficiency leads to
xerophthalmia
keratinization of the cornea and
blindness
81

82. Bitot’s spot Bitot’s spot

83. KeratomalaciaXerophthalmia

84. Vitamin A
ANTI-INFECTIVE VITAMIN
REQUIRED FOR NORMAL
FUNCTIONING OF THE
IMMUNE SYSTEM
84

85. SKIN AND MUCOSAL CELLS
FUNCTION AS A BARRIER AND
FORM THE BODY'S FIRST LINE
OF DEFENSE AGAINST
INFECTION.
• RETINOL AND ITS METABOLITES
ARE REQUIRED TO MAINTAIN THE
INTEGRITY AND FUNCTION OF
EPITHELIAL CELLS
85

86. 86

87. VITAMIN A
CONTROLS
KERATIN
PRODUCTION
87

88. 88

89. 89

90. 90

91. Important Role In
Differentiation Of Immune System Cells
CENTRAL ROLE IN THE
DEVELOPMENT
AND
DIFFERENTIATION
of white blood cells
such as
LYMPHOCYTES 91

92. Important Role In
Differentiation Of Immune System Cells
EVEN MILD DEFICIENCY
LEADS TO INCREASED
SUSCEPTIBILITY TO
INFECTIOUS DISEASES
92

93. 93

94. • Red capsule 200000 IU (60 mg RE) 12-59
months of age , blue capsule 100000 IU (30
mg RE) 6-11 months of age twice yearly
(WHO RECOMMENDATION)
• SIDE EFFECTS bulging of open fontanelles in
younger infants
• Nausea / vomitting , headache in older
children

95. 95

96. Growth and development
Both Vitamin A Excess And
Deficiency
Cause Birth Defects
Retinol
And
Retinoic Acid
ESSENTIAL
FOR
EMBRYONIC DEVELOPMENT 96

97. Red blood cell production
97

98. VITAMIN A TOXICITY
HYPERVITAMINOSIS
A
98

99. Vitamin A Is Toxic In Excess
• Limited Capacity To
Metabolize Vitamin A
• Excessive Intakes Lead To
Accumulation Beyond The
Capacity Of Binding
Proteins
99

100. Vitamin A Is Toxic In Excess
Hypervitaminosis A
• Unbound Vitamin A Causes
• Membrane lysis
• Tissue damage
100

101. Vitamin A Is Toxic In Excess
Hypervitaminosis A
Caused By
Overconsumption Of
Preformed Vitamin A
Not Carotenoids
101

102. Increased Consumption Of
Caroteinoids
102

103. 103

104. Vitamin A Is Toxic In Excess
Hypervitaminosis A
Preformed Vitamin A
Rapidly Absorbed
Slowly Cleared
From The Body
104

105. One ounce of
polar bear
liver contains
enough
vitamin A
(retinol) to kill
a person!

106. Vitamin A Is Toxic in Excess
hypervitaminosis A
Symptoms
• Central Nervous System
Increased intracranial
pressure
• Headache
• Nausea
• Ataxia
And
• Anorexia 106

107. Vitamin A Is Toxic in Excess
hypervitaminosis A
• LIVER
Hepatomegaly
• CALCIUM HOMEOSTASIS
Thickening Of The Long Bones
Hypercalcemia
And
Calcification Of Soft Tissues
107

108. Vitamin A Is Toxic in Excess
hypervitaminosis A
• SKIN
excessive drynes
desquamation
and
alopecia
108

109. 109

110. 110

113. 113