This document summarizes fat-soluble vitamins, focusing on vitamin A. It discusses that vitamin A exists in retinol, retinal, and retinoic acid forms. Retinol is stored in the liver and transported via retinol binding protein. Retinoic acid regulates gene expression by binding to nuclear receptors. Vitamin A is important for vision, epithelial tissue integrity, growth, reproduction, and acting as an antioxidant. Good sources are animal foods like liver, while plant foods like carrots contain provitamin A carotenoids.

1. Fat-soluble Vitamins
R. C. Gupta
Professor and Head
Dept. of Biochemistry
National Institute of Medical Sciences
Jaipur, India

2. • Include vitamins A, D, E and K
• Are soluble in fat but insoluble in
water
• Are present in food in association
with dietary lipids
• Can be stored in the body and their
excessive intake can be toxic
Fat-soluble vitamins:

3. Vitamin A
Vitamin A is found only in animals though
its precursors are found in a variety of
plants
Chemically, it is made up of a b-ionone
ring attached to a polyene chain

4. Vitamin A occurs in three forms:
• Retinol (alcohol form)
• Retinal (aldehyde form)
• Retinoic acid (acid form)

5. HH H H
CH3
CH3
CH3
|
|
|
H
H
H
|
|
|
C
C
C
1
2
3
4
5
6
7
8
CH3
CH3
CH3
CH3
CH3
CH3
C
C
C
CH3
CH3
CH3
|
|
|
C
C
C
9 10
C
C
C
H
H
H
|
|
|
C
C
C
11
12
C
C
C
|
|
|
C
C
C
13 14
C
C
C
CH OH2
CHO
COOH
15
CH3
CH3
CH3
Retinol
Retinal
Retinoic acid
HH H H
HH H H

6. All the double bonds in the polyene chain
have a trans-configuration
Hence, the naturally occurring vitamin A
is all-trans-vitamin A

7. Retinol may be esterified with a fatty acid
or phosphoric acid
The storage form of vitamin A is generally
retinyl palmitate
Some of the functions of vitamin A are
performed by retinyl phosphate

8. Vitamin A can be formed in our body from
its precursors (provitamins A)
The precursors are carotenes (or
carotenoids)
These are naturally occurring pigments
They are found in most yellow and green
fruits and vegetables

9. a-Carotene, b-carotene and g-carotene are
important precursors of vitamin A
a-Carotene
b-Carotene
g-Carotene

10. b-carotene is the most important precursor
b-Carotene is made up of two b-ionone rings
connected by an 18-carbon polyene chain
One molecule of b-carotene can be
converted into two molecules of retinal

11. b-Carotene is cleaved in the middle by
b-carotene dioxygenase and O2
Two molecules of retinal are formed
Bile salts facilitate this reaction

12. b-Carotene
[O ]2
b-Carotene dioxygenase,
bile salts
Retinol
NADPH + H
+
NADP+
Retinaldehyde reductase
(retinene reductase)
CH3
|
C
CH3
CH3
C
H
|
H C3
C
C
H
|
C
C
H
|
C
C
H
|
CH3 CH3
| | | |
H H H H H
| | | | |
H H H C3
C
C
H
|
C
C
|
C
C
H
|
C
C
|
C
C
H
|
CH3CH3
CH3
|
C
CH3
CH3
C
H
|
H C3
C
C
H
|
C
C
H
|
C
C
H
|
CH3 CH3
| | | |
H H H H
| | | |
H H H C3
CHO
OHC
C
C
|
C
C
H
|
C
C
|
C
C
H
|
CH3CH3
+
CH3
|
C
CH3
CH3
C
H
|
C
C
H
|
C
C
H
|
C
C
H
|
CH3
CH3
| |
H H
| |
CH OH2
Retinoic acid
Spontaneous
[O]
CH3
CH3
| | |
H H
| |
C
C
H
|
C C
C C
| |
C
C
H
|
CH3
CH3 CH3
COOH
H H
|
CH3
|
CH3
Retinal Retinal

13. Retinal is reduced to retinol by
retinaldehyde (retinine) reductase
Some retinal is spontaneously oxidized to
retinoic acid
Retinal and retinol are inter-convertible
However, retinoic acid cannot be converted
back into retinal

14. a-Carotene and g-carotene contain only
one b-ionone ring
Therefore, they can form only one retinal
molecule each

15. Carotenes are split into retinal which is
converted into retinol in the small intestine
Dietary retinyl esters are hydrolysed to
form retinol
Retinol is absorbed from the small intestine
Absorption, transport and storage

16. Retinol is taken up by the mucosal cells
It is esterified with fatty acids
Esterified retinol enters the lacteals and
reaches liver via circulation

17. Retinol is stored in the hepatic lipocytes
When needed, it is released from liver into
circulation
It is transported in blood by an a1-globulin,
retinol binding protein (RBP)

18. Circulating retinol is taken up by the cells
that need it
In the cells, it is bound to cellular retinol
binding protein (CRBP)

19. Retinoic acid formed in the intestine is also
absorbed
Retinoic acid is transported in circulation
by albumin
A small amount of carotenes may also be
absorbed
Carotenes are transported by chylomicrons

20. Vitamin A received its name from its
relationship with retina
But its functions are wide-ranging, and
extend beyond retina
Functions

21. Retinal and retinol are inter-convertible
They can also be converted into retinoic
acid
Hence, they can perform all the functions
of vitamin A

22. Some effects of vitamin A occur via
expression of genes
Regulation of gene expression is the
function of retinoic acid alone
Retinoic acid is present in cells as all-trans-
retinoic acid and 9-cis-retinoic acid

23. Both the forms of retinoic acid are
transported from cytosol to the nucleus
Cellular retinoic acid-binding protein
(CRABP) is their transporter within the cell
After reaching the nucleus, retinoic acids
bind to their specific receptors

25. The receptor for all-trans-retinoic acid is
known as retinoic acid receptor (RAR)
Receptor for 9-cis-retinoic acid is known as
retinoid X receptor (RXR)
RAR and RXR bind their ligands and then
form RAR/RXR heterodimers

26. RAR/RXR heterodimer binds to a specific
sequence in DNA
This sequence is known as retinoic acid
response element (RARE)
Binding of RAR/RXR to RARE regulates
the expression of downstream genes

27. RA
Initiation of
transcription
RARE
RAR RXR
DNA

28. RXR can also form heterodimers with
thyroid hormone receptor and vitamin D
receptor
Therefore, vitamin A, vitamin D and
thyroid hormone can interact with each
other in regulating gene expression

29. Retinoic acid stimulates/inhibits the
transcription of specific genes
Thereby, it plays a role in cellular
differentiation
Several functions of vitamin A result from
its effect on cellular differentiation

30. Functions of vitamin A are related to:
• Reproduction
• Growth and differentiation
• Integrity of epithelial tissues
• Vision
• Anti-oxidant role
• Anti-carcinogenic role

31. Reproduction
Vitamin A deficiency has been observed
to impair reproductive function in some
animals
This function is probably mediated by
control of expression of certain genes by
retinoic acid

32. Growth and differentiation
Vitamin A is required for normal growth
and differentiation of tissues
Formation of bones and soft tissues is
impaired in animals deficient in vitamin A
Vitamin A is probably required for the
synthesis of mucopolysaccharides and
glycoproteins in various tissues

33. Integrity of epithelial tissues
Vitamin A maintains the integrity of epithelial
tissues
Epithelial tissues of eyes, lungs, gastro-
intestinal tract and genitourinary tract
become dry and keratinized in vitamin A
deficiency

34. Vision
Role of vitamin A in vision was shown by
Morton and Wald
Retina contains two types of photo-
receptor cells
These are known as rod cells and cone
cells

35. Rod cells are required for dim light vision
Cone cells are required for bright light
vision and for perception of colours
Vitamin A is essential for the functioning
of rod cells as well as cone cells

36. Rod
cell
Cone
cells

37. Rod cells contain a pigment, rhodopsin
(visual purple)
This is a conjugated protein made up of
opsin and 11-cis-retinal
Opsin is a protein and 11-cis-retinal is an
isomer of all-trans-retinal

38. Rhodopsin molecules are present in large
numbers in rod cells
When light strikes rod cells, 11-cis-retinal is
converted into all-trans-retinal
Rhodopsin

39. Conformation of all-trans-retinal is such
that it cannot bind with opsin
Therefore, opsin and all-trans-retinal
dissociate
A number of transient intermediates are
formed before their dissociation

40. On moving from dim light to bright light, all
rhodopsin molecules are rapidly dissociated
When the person moves back into dim light,
he cannot see until rhodopsin is re-formed
For this, all-trans-retinal has to be
isomerized to 11-cis-retinal

41. The enzyme for isomerization of retinal is
present only in liver
All-trans-retinal is first reduced to all-trans-
retinol in retina
All-trans-retinol is released into circulation

42. Circulating all-trans-retinol is taken up by
liver
It is isomerized to 11-cis-retinol
11-cis-Retinol is released into circulation

43. Retina takes up the circulating 11-cis-
retinol and oxidizes it to 11-cis-retinal
11-cis-Retinal combines with opsin to form
rhodospin
This sequence of reactions is known as
visual cycle

44. Rhodopsin
Light Light
Bathorhodopsin Lumirhodopsin
Metarhodopsin I
Metarhodopsin II
Opsin
All- -retinaltrans
All- -retinoltrans
All- -retinoltrans
II- -Retinalcis
II- -Retinolcis
II- -Retinolcis
NADPH + H
+
Retinine reductase
NADP+
via
circulation
via
circulation
Retinol isomerase
RETINA
LIVER
Light
Light
Light

45. The time taken for regeneration of rhodospin
is known as dark adaptation time
This depends upon vitamin A content of liver
When liver contains adequate stores of
vitamin A, dark adaptation time is short
In vitamin A deficiency, dark adaptation time
is prolonged

46. Mechanism of vision
Rhodopsin is a trans-membrane protein
When photons strike it, they convert 11-
cis-retinal into 11-trans-retinal (all-trans-
retinal)
As a result, rhodopsin molecule is
activated (photo-excited)

47. All-trans-retinal
11-cis-
Retinal
Photon
Rhodopsin Photo-excited
rhodopsin

48. The photo-excited form of rhodopsin is
probably meta-rhodopsin II
Another membrane-bound protein, trans-
ducin is present in vicinity of rhodopsin
Transducin belongs to the family of G-
proteins

49. Transducin is made up of three subunits -
a-subunit, b-subunit and g-subunit
a-Subunit has a site that can bind GDP or
GTP
Normally, this site is occupied by GDP

50. When rhodopsin is photo-excited, it
displaces GDP by GTP in transducin
The a-subunit containing GTP dissociates
from the b- and g-subunits
It binds to and activates the enzyme,
cGMP phospho-diesterase

51. Active cGMP phospho-diesterase converts
cGMP into GMP
Decreased cGMP concentration affects
cation-specific channels in the rod cell
membrane

52. Rod cell membrane contains a number of
cation-specific channels
Normally, these are kept open by cGMP
Open channels permit continuous influx of
sodium ions into the rod cell

53. Open Closed
Na+2
Ca+2
Cation-specific channels

54. Decrease in cGMP concentration leads to
closure of cation-specific channels
Sodium ions accumulate outside the rod
cell
This causes hyperpolarization of the rod
cell membrane

55. Rhodopsin
Light Photo-excited
rhodopsin
GTP-a-subunit b- and g-subunit
cGMP GMP
Inactive cGMP
phosphodiesterase
Active cGMP
phosphodiesterase
Open cation-specific
channels
Closed cation-specific
channels
Normal
membrane
Hyperpolarized
membrane
GDP-transducin GTP-transducin

56. Hyperpolarization generates a nerve
impulse
The nerve impulse is transmitted to
visual cortex of brain
Visual cortex perceives the image

57. The a-subunit of transducin possesses
intrinsic GTPase activity
Therefore, GTP bound to the a-subunit is
slowly hydrolysed into GDP
When GTP is converted into GDP, a-
subunit dissociates from cGMP phospho-
diesterase

58. The a-subunit re-associates with b- and g-
subunits
Transducin containing GDP is re-formed
cGMP phospho-diesterase becomes
inactive
The chain of events generating the nerve
impulse is terminated

59. Vitamin A is required for bright light vision
also
Bright light vision is the function of cone
cells
Cone cells contain some photo-sensitive
proteins

60. Photo-sensitive proteins in cone cells are
porphyrinopsin, iodopsin and cyanopsin
These are sensitive to red, green and blue
light respectively
Prosthetic group is 11-cis-retinal in each of
these but the protein part is different

61. Light of a specific colour photo-excites
porphyrinopsin, iodopsin or cyanopsin
A nerve impulse is, then, generated in the
same way as in rod cells

62. A given cone cell contains only one of the
three photo-sensitive proteins
It can perceive only one particular colour
An inherited absence of, or defect in, these
proteins causes colour blindness

63. b-Carotene acts as an anti-oxidant
It prevents lipid peroxidation at low oxygen
tension
Anti-oxidant role

64. Some epidemiological studies have shown
a relationship between certain cancers and
low intake of vitamin A or carotenes
However, this relationship is not yet
experimentally and clinically confirmed
Anti-carcinogenic role

65. Preformed vitamin A is present only in
animal foods
Good sources are fish, liver, meat, eggs,
milk and milk products
Sources

66. Sources of vitamin A
Liver
ButterMilkEggs
MeatFish

67. Provitamins A are found in:
Green leafy vegetables
Red and yellow vegetables and fruits

68. SpinachCarrots
Tomatoes
Pumpkin
Peaches Papaya
Mangoes
Cabbage
Sources of
provitamin A

69. Requirement
Vitamin A is present in food in several
different forms
These forms differ in their vitamin A
activity
Therefore, it is not possible to express the
requirement in terms of actual weight

70. Relative vitamin A activities of different
compounds were compared in rats
The activities were expressed in terms of
international units (IU)

71. One IU is the activity present in:
• 0.3 µg of retinol or
• 0.344 µg of retinyl acetate or
• 0.6 µg of b-carotene

72. Daily requirements were expressed in IU for
a long time
Later, it was found that absorption/utilization
of carotenes were less efficient in man
Therefore, vitamin A activities were
converted into retinol equivalents (RE)

73. One RE is the activity present in:
• 1 µg of retinol or
• 6 µg of b-carotene or
• 12 µg of other carotenes

74. The daily requirement of vitamin A in
terms of IU and RE is:
IU/day RE/day
Infants 1,500-2,000 350
Children 2,000-4,000 400-600
Adult men 5,000 600
Adult women 4,000 600
Pregnant women 5,000 800
Lactating women 6,000 950

75. Deficiency of vitamin A can arise from:
• Inadequate intake
• Inadequate absorption
• Poor conversion of carotenes into retinal
Zinc deficiency may impair the mobilization
of vitamin A from liver
Deficiency

76. The clinical manifestations of
deficiency are:
• Xerophthalmia
• Keratomalacia
• Nyctalopia
• Blindness
• Follicular hyperkeratosis
• Susceptibility to infections

77. Xerophthalmia
The lacrimal glands become keratinized,
and stop secreting lacrimal fluid
The eyes become dry
Bitot’s spots (small, opaque spots) may
appear on cornea

78. Bitot’s spot

79. Keratomalacia
The cornea is softened
It is finally destroyed

80. Nyctalopia
Initially, dark adaptation time is prolonged
This may be the earliest indication of
deficiency
Finally, the ability to see in dim light is
completely lost
This is known as nyctalopia or night
blindness

81. Blindness
In severe and prolonged deficiency,
there is total loss of vision
Blindness occurs due to functional
and structural changes in the eyes

82. Follicular hyperkeratosis
There is hyperkeratinization of skin
especially around hair follicles

83. Susceptibility to infections
Susceptibility to infections may be
increased due to epithelial damage

84. Vitamin A toxicity
Hypervitaminosis A may occur if large
doses of vitamin A in pharmacological form
are taken over long periods

85. Hypervitaminosis A is characterized by:
• Rough skin
• Hair loss
• Anorexia
• Weight loss
• Headache
• Vertigo
• Irritability
• Hyperaesthesia
• Hepatosplenomegaly
• Liver damage etc

86. Vitamin D
Vitamin D prevents rickets (rachitis), a
deficiency disease
It is also known as anti-rachitic factor
or anti-rachitic vitamin

87. Several compounds possess vitamin D
activity
The most important are:
• Vitamin D2 (ergocalciferol)
• Vitamin D3 (cholecalciferol)

88. Vitamin D2 is formed from provitamin D2
(ergosterol) on exposure to ultraviolet light
Vitamin D3 is formed from provitamin
D3 (7-dehydrocholesterol) on exposure to
ultraviolet light

89. CH3
CH3
CH3
CH3
CH3
H3C
HO HO
H3C
CH3
CH3
CH3
CH2
Ergosterol Ergocalciferol (vitamin D2)
Ultraviolet
light
CH3
CH3
CH3
CH3
H3C
HO HO
H3C
CH3
CH3
CH3
CH2
7-Dehdrocholesterol Cholecalciferol (vitamin D3)
Ultraviolet
light
CH3

90. Ergosterol occurs in plants e.g. ergot and
yeast
7-Dehydrocholesterol occurs in animals
including human beings

91. 7-Dehydrocholesterol is formed from
cholesterol
7-Dehydrocholesterol present in skin is
converted into cholecalciferol on
exposure to sunlight

92. Intestinal absorption of calcium and
phosphorus
Renal tubular absorption of calcium
Mineralization of bones
EMB-RCG
Functions

93. Vitamin D increases intestinal absorption
of calcium
Absorption of phosphorus is increased
secondarily
Vitamin D increases renal tubular
absorption of calcium, and decreases that
of phosphorus

94. Vitamin D is required for mineralization of
bones
Bone formation is a continuous and
dynamic process
Calcium salts are continuously deposited
into bones by osteoblasts
They are resorbed from bones by
osteoclasts

96. Deposition exceeds resorption in growing
age, leading to skeletal growth
Deposition and resorption are balanced in
adult life, leading to remodeling of bones
Vitamin D is required for bone growth as
well as remodeling

97. Thus, the main functions of vitamin D are:
• Regulation of calcium metabolism
• Mineralization of bones
However, these functions are not
performed by vitamin D itself

98. Vitamin D is first hydroxylated at C25 to
form 25-hydroxycholecalciferol
25-Hydroxycholecalciferol is hydroxylated
at C1 to form 1,25-dihydroxycholecalciferol
The first hydroxylation occurs in liver and
the second in the kidneys

99. 1,25-Dihydroxycholecalciferol (1,25-DHCC)
is also known as calcitriol
1,25-DHCC is the metabolically active form
of vitamin D
1,25-DHCC acts as a hormone; hence
vitamin D is regarded as a prohormone

100. Mechanism of action of calcitriol is similar
to that of steroid hormones
Vitamin D receptors (VDRs) are located
inside the cells
VDR and RXR form a dimer
Calcitriol binds to VDR in the target cells

101. Calcitriol
Initiation of
transcription
VDRE
VDR RXR
DNA

102. Calcitriol-VDR-RXR complex binds to
vitamin D response element (VDRE) in DNA
This increases the transcription and
translation of certain genes
The gene products perform the actual
functions

103. Cholecalciferol
Hydroxylase
25-Hydroxycholecalciferol
Parathormone Parathyroid
glands
1, 25-Dihydroxycholecalciferol
Induction
Calcium-binding protein
Ca -dependent ATPase
Alkaline phosphatase
++
Calcium absorption Release into circulation
Plasma calcium
LIVER
KIDNEY
INTESTINAL
MUCOSA
Hydroxylase
INTESTINAL
MUCOSA

–
 
+

104. Sources
Plant foods are poor sources of vitamin D
Though ergocalciferol is present in some
plants, its intestinal absorption is poor
Cholecalciferol is the major dietary form
of vitamin D

105. Sources of
vitamin D
Liver
MushroomsSoyaCheese
Milk
Eggs
Butter
Fish

106. An important source of vitamin D is its
endogenous synthesis
If sunshine is good and exposure to
sunlight is adequate, enough vitamin D is
synthesized in the body

107. Requirement
Anti-rachitic activity of different forms of
vitamin D is different
Hence, the requirement is expressed in
international units (IU)
One IU is the activity present in 0.025 µg
of cholecalciferol

108. The requirement is 400 IU/day irrespective
of age and sex
Endogenous synthesis can meet up to
90% of the requirement

109. Deficiency
Deficiency of vitamin D can occur
due to:
• Inadequate intake
• Inadequate absorption
• Inadequate exposure to sunlight

110. Two distinct syndromes arise
from deficiency of vitamin D:
• Rickets in childhood
• Osteomalacia in adult life

111. Rickets
Ricket occurs mostly during infancy and
puberty
These are the periods of rapid skeletal
growth

112. Deficiency of vitamin D causes:
• Deficient mineralization of bones
• Overgrowth of epiphyses
This results in some typical skeletal
deformities

113. Delayed closure of fontanelles
Closure of fontanelles is delayed in rickets
This can cause bossing of the skull

114. Craniotabes
Skull bones are soft due to poor
mineralization
This is known as craniotabes

115. Pigeon chest
Antero-posterior diameter
of chest is increased
This gives the appearance
of pigeon chest

116. Rickety rosary
Enlarged
costochondral
junctions
Costochondral junctions of ribs are
enlarged, and appear to the beaded
The series of beads on the chest
looks like a rosary worn around the neck

117. Vertebral deformities
Kyphosis, lordosis or scoliosis can occur
Kyphosis is forward bending of vertebral
column
Lordosis is backward bending of
vertebral column
Scoliosis is lateral bending of vertebral
column

118. Kyphosis LordosisScoliosis

119. Pelvic deformities
Pelvis may be deformed in rickets
The size of the pelvic outlet may be
decreased

120. The leg bones may become
curved under the weight of
the body (bowlegs)
The two knees may touch
each other while standing
erect (knock knees)
Bowlegs and knock knees

121. Enlarged wrists and knees
Wrists and knees may be enlarged due
to overgrowth of epiphyses of the long
bones

122. The combination of
skeletal deformities
may cause shortening
of stature

123. Some changes in serum and urine
chemistry are also seen
Serum calcium and inorganic phosphorus
are decreased
Serum alkaline phosphatase is increased

124. Hypocalcaemia increases the secretion of
parathormone
Parathormone decreases the urinary
excretion of calcium, and increases that
of phosphorus

125. Osteomalacia
Pregnant and lactating women are
particularly prone to osteomalacia
Demineralization of bones occurs to
varying extents

126. Aches and pains may occur in bones in
osteomalacia
Susceptibility to fractures is increased
Changes in serum and urine chemistry are
similar to those in rickets

127. Toxicity
Excessive intake of vitamin D may
cause hypervitaminosis D
This occurs after prolonged intake of
large doses of vitamin D in pharma-
cological form
Serum calcium is raised in hyper-
vitaminosis D

128. Hypercalcaemia can cause:
• Loss of appetite
• Polydipsia
• Polyuria
• Constipation
• Muscular weakness

129. Calcification may occur in soft tissues e.g.
arteries, bronchi, muscles, kidneys etc
Stones may be formed in the kidneys

130. Vitamin E
Vitamin E is sometimes described as anti-
sterility vitamin
But its anti-sterility function is seen only in
some animals and not in human beings

131. Vitamin E activity is present in several
tocopherols
The most important are a-, b-, g- and d-
tocopherols

132. O
O
O
O
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
H3C
H3C
HO
HO
HO
HO
18
2
3
45
6
7
(CH2)3‒CH‒(CH2)3‒CH‒(CH2)3‒CH‒CH3
(CH2)3‒CH‒(CH2)3‒CH‒(CH2)3‒CH‒CH3
(CH2)3‒CH‒(CH2)3‒CH‒(CH2)3‒CH‒CH3
(CH2)3‒CH‒(CH2)3‒CH‒(CH2)3‒CH‒CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
a-Tocopherol
b-Tocopherol
g-Tocopherol
d-Tocopherol
CH3
CH3
CH3
CH3

133. a-Tocopherol is the most abundant
tocopherol, and is taken as the standard
The official reference standard is synthetic
DL-a-tocopherol acetate
Activity present in 1 mg of this compound
is taken as one international unit (IU)

134. The vitamin E activity of 1 mg of naturally-
occurring D-a-tocopherol is 1.5 IU
Vitamin E activities of other tocopherols
are much lower

135. Functions
The most important function of vitamin E
in human beings is as an anti-oxidant
Vitamin E is readily oxidizable
It prevents the oxidation of other, less
oxidizable, compounds

136. Vitamin E prevents the oxidation
of other antioxidants such as:
• Carotenes
• Vitamin A
• Vitamin C

137. Unsaturated fatty acids are prone to
peroxidation
–CH=CH–CH2–
O2
–CH=CH–CH(OOH)–

138. Vitamin E prevents the peroxidation of
unsaturated fatty acids
This protects the tissues against the
harmful effects of lipid peroxides

139. Vitamin E protects the erythrocyte
membrane from oxidants
This makes erythrocytes resistant to
haemolysis
Vitamin E protects the pulmonary tissue
from atmospheric oxidants

140. Sources of vitamin E
Vegetable oils Soya bean Corn
FruitsNuts Green leafy vegetables

141. Infants 4-5 IU/day
Children 7-12 IU/day
Adult men 15 IU/day
Adult women 12 IU/day
Pregnant and
lactating women 15 IU/day
Requirement

142. Requirement of vitamin E is related to the
intake of polyunsaturated fatty acids
(PUFA)
An intake of 1.2 IU of vitamin E per gm of
PUFA in diet will prevent vitamin E
deficiency

143. Deficiency
Deficiency of vitamin E is uncommon
because of its widespread distribution in
foods
Moreover, the foods which are rich in
PUFA, e.g. vegetable oils, are also rich in
vitamin E

144. Deficiency of vitamin E may occur in:
• Severely undernourished children
• Premature infants fed on artificial milk
not containing vitamin E

145. The clinical manifestations
of deficiency are:
• Oedema
• Haemolytic anaemia
• Thrombocytosis

146. Vitamin K
Vitamin K activity is present in compounds
having 2-methyl-1,4-naphthoquinone nucleus
Two such natural compounds are phyllo-
quinone (vitamin K1) and menaquinone
(vitamin K2)
The former occurs in plants and the latter in
bacteria

147. 2-Methyl-3-phytyl-1,4-naphthoquinone (Phylloquinone)
‒CH2‒CH=C‒(CH2)3‒CH‒(CH2)3‒CH‒(CH2)3‒CH‒(CH2)3
‒CH3
O
O
2
1
4
3
CH3
CH3 CH3
2-Methyl-3-difarnesyl-1,4-naphthoquinone (Menaquinone)
‒CH2‒(CH=C‒CH2)5‒CH=C‒(CH3)2
‒CH3
O
O
CH3

148. Some synthetic compounds having
vitamin K activity are also available
These are menadione, sodium menadiol
diphosphate and menadione sodium
bisulphite
These three are water-soluble

149. O
O O
O
O–P=O
‫׀‬
–CH3 –CH3 –CH3
SO3Na
O–P=O
ONa
‫׀‬
‫׀‬
‫׀‬
ONa
ONa
ONa
Sodium menadiol
diphosphate
Menadione
sodium bisulphite
Menadione

150. Functions
Vitamin K is essential for normal
coagulation of blood
Plasma levels of several coagulation
factors are decreased in vitamin K
deficiency
These include prothrombin, proconvertin,
Christmas factor and Stuart-Prower Factor

151. All these coagulation factors are proteins
They require some post-translational
modification for their activation
Vitamin K is required for the post-
translational modification

152. Prothrombin is synthesized in liver as an
inactive precursor, pre-prothrombin
Pre-prothrombin is converted into pro-
thrombin by carboxylation of its glutamate
residues
Hydroquinone (reduced) form of vitamin K
is required for the carboxylation reaction

153. During hydroxylation, hydroquinone form of
vitamin K is converted into 2,3-epoxide form
Hydroquinone form is regenerated by 2,3-
epoxide reductase and vitamin K reductase
A sulphydryl compound is required in the
reaction catalysed by 2,3-epoxide reductase

154. COOH
|
CH2
|
CH2
|| ||
— N — CH — C —
Glutamate residue
H O
| ||
— N — CH — C—
g-Carboxyglutamate residue
H O
Vitamin K-dependent
carboxylase
H O2
Vitamin K
(hydroquinone form)
CO + O2 2
OH
|
—CH3
—R
|
OH
Vitamin K
(2,3-epoxide form)
O
||
||
—CH3
—R
O
O
Vitamin K
reductase
NADP+
NADPH + H
+
2,3-Epoxide reductase
Dicoumarol
R
SH
SH
–
|
CH2
|
HOOC COOH
CH
R
S
+ H O2

Vitamin K
(quinone form)
—CH3
—R
||
||
O
O 
S

155. At normal pH, the carboxyl groups
attached to the g-carbon of carboxy-
glutamate residues are ionized
The two negatively charged carboxyl
groups act as a Ca+2-binding site
CH
CH2
CHN
H
C
O
COOOOC

156. Thus, the function of vitamin K is to create
Ca++-binding sites on prothrombin
As a result of this, prothrombin become
biologically active
Similar sites are probably created by
vitamin K on Factors VII, IX and X also

157. Sources
Green leafy vegetables (alfalfa, spinach,
cabbage etc) are rich in vitamin K
Nuts, cauliflower and peas are good
sources
Small amounts are present in liver, milk
and eggs

158. Sources of
vitamin K
Green
leafy
vegetables
Cauliflower Cabbage
PeasNuts
Liver Eggs Milk

159. A very important source of vitamin K is
bacterial synthesis in the intestine
Intestinal bacteria synthesize a good deal
of vitamin K which is available to the host

160. Requirement
Exact requirement is unknown as intestinal
bacteria provide sufficient vitamin K
Vitamin K supplements are required only
when:
• Intestinal bacteria are destroyed
• Fat absorption is impaired
The requirement is probably less than 0.1
mg/day

161. Deficiency
Deficiency of vitamin K disturbs
coagulation of blood
Slight injury can cause prolonged
bleeding in vitamin K deficiency
Diagnosis can be made by measuring
prothrombin time

162. Prothrombin time is prolonged in vitamin K
deficiency
Prothrombin time may be prolonged in
liver damage also
This is due to inability of liver to synthesize
prothrombin

163. Distinction between vitamin K deficiency
and liver damage can be made by
parenteral administration of vitamin K
Prothrombin time returns to normal in
subjects deficient in vitamin K but not in
patients with liver damage