Vitamin D, A, K, and E are fat soluble vitamins that serve important biochemical functions. Vitamin D helps regulate calcium and phosphate levels. It is synthesized when skin is exposed to sunlight and is also obtained through dietary sources like fish and fish liver oils. Vitamin A supports vision, reproduction, growth and epithelial tissue maintenance. Vitamin K is a cofactor for blood clotting proteins. Vitamin E is a powerful antioxidant that protects cell membranes from oxidative damage.

1. Fat Soluble
vitamins
Binaya Tamang
UCMS-TH
Bhairahawa

2. Vitamins
a group of organic nutrients required in
small quantities for a variety of biochemical
functions and which, generally, cannot be
synthesized by the body and must therefore
be supplied in the diet.

3. 4 important lipid-soluble
vitamins, D, A, K, and E.

4. Vitamin ‘D’

5. • The provitamin of vitamin D2 is ergosterol which is found
in ergot and yeast.
• The provitamin of vitamin D3 is dehydrocholesterol which
is found in animals.
(sunshine vitamins.)
• The provitamins are converted to active forms on
exposure to ultraviolet light present in sunlight or in any
other light.
• The conversion involves opening of B-ring of steroid
nucleus

6. Dietary sources
• sources of vitamin D include
• fish, fish liver oils, egg yolk etc.
• Milk is not a good source of vitamin D.

7. Absorption, transport and storage
• Vitamin D is absorbed in the small intestine for which
bile is essential.
• Through lymph, vitaminD enters the circulation bound
to plasma a2-globulin and is distributed throughout the
body.
• Liver and other tissues store small amounts of vitamin D.

8. Recommended dietary
allowance (RDA)
• The daily requirement of vitamin D is 400 IU or 10 mg of
cholecalciferol.
• In countries with good sunlight (like India) the RDA for
vitamin D is 200 lU (or 5 mg of cholecalciferol)

9. Formation of Vitamin D
• During the course of cholesterol biosynthesis,
7-dehydrocholesterol is formed as an intermediate.
• On exposure to sunlight,
• 7-dehydrocholesterol is converted to cholecalciferol in the
skin (dermis and epidermis)
• Malpighian layer of epidermis.

10. Synthesis of 1,25-DHCC
• Cholecalciferol is first hydroxylated at 25th position to
form
• 25hydroxycholecalciferol(25-OH D3) by enzyme liver.
25-hydroxylase
• 25-OH D3 is the major storage and circulatory form of
vitamin D.
• Kidney : 1–hydroxylase.
• hydroxylates 25-hydroxycholecalciferol at position 1 to
produce 1,25- dihydroxycholecalciferol (1,25-DHCC).
• 1,25 DHCC contains 3 OH groups (1,3 and 25 ) hence
referred to as calcitriol.
Require cytochrome P450, NADPH and molecular oxygen for
the hydroxylation process.

12. Regulation
• The concentration of 1,25-DHCC is regulated by plasma levels
of calcium and phosphate.
• They control hydroxylation reaction at position.
Low plasma phosphate
increases the activity of 1- hydroxylase of kidney
Low plasma calcium
enhances the production of parathyroid hormone
which in turn activates 1-hydroxylas
• Thus the action of phosphate is direct while that of calcium is
indirect on kidney 1-hydroxylase.

13. Biochemical functions
• Calcitriol ( 1,25-DHCC) is the biologically active form of
vitamin
• lt regulates the plasma Levels of calcium and phosphate.
Calcitriol acts
at 3 different levels
1. intestine
2. kidney
3. bone
• Maintain plasma calcium
( normal =9 -11 mg/dl).

14. Action on the intestine

15. Action on the bone
• In the osteoblast of bone, calcitriol stimulates calcium
uptake for deposition of calcium and phosphate
• Thus calcitriol is essential for bone formation
• Calcitriol along with parathyroid hormone(PTH)
increases the mobilization of calcium and phosphate
from the bone.
• This causes elevation in the
• plasma calcium and phosphate levels

16. Action on the kidney
• Calcitriol is also involved in minimizing the excretion of
calcium and phosphate
through the kidney,
by decreasing their excretion
and enhancing reabsorption.
• Ultimately leading to the increase in plasma calcium

18. Vitamin D is a hormone and
not a vitamin-justification

19. 24, 25-hydroxy cholecalciferol
• In kidney under normal conditions it is hydroxylated at
24-position by 24-hydroxylase to
• 24-25 hydroxy calcitriol.
• The exact function of 24,OH-DHCC is not know
• when calcitriol concentration is adequate,>>>>>>a less
important compound 24,25-DHCC.
• In this way, to maintain the homeostasis of calcium,
• Synthesis of 24,25-DHCC is also important

20. Deficiency symptoms
Rickets in children:
bone deformities due to incomplete
mineralization, resulting in soft and pliable bones
and delay in teeth formation. Bow legs, low
calcium level and ALP is increased
• Osteomalacia in adults.
• Osteoporosis in old people.

21. Renal rickets
(renal osteodystrophy)
• This is seen in patients with chronic renal failure.
• Renal rickets is mainly due to decreased synthesis of
calcitriol in kidney.
lt can be treated by administration of calcitriol.

22. Hypervitaminosis D
• Among the vitamins
• vitamin D is the most toxic in overdoses
• demineralization of bone (resorption) and
hypercalcemia.
• deposition of calcium in many soft tissues such as
kidney and arteries
• renal calculi

23. VITAMIN K

24. Discovery
• as a result of investigations into the cause of a
bleeding disorder—hemorrhagic (sweet clover)
disease—of cattle, and of chickens fed on a fat-free
diet.
• The missing factor in the diet of the chickens was
vitamin K, while the cattle feed contained
dicumarol, an antagonist of the vitamin.

25. Three compounds
Phylloquinone, the
normal dietary source,
found in green vegetables.
menaquinones,
synthesized by intestinal
bacteria, with differing
lengths of side-chain;
menadione,
 menadiol, and
menadiol diacetate

26. Function
•Vitamin K Is the Coenzyme
for Carboxylation of
Glutamate
in the Post synthetic
Modification
of Calcium-Binding Proteins

30. Examples of proteins undergoing this
vitamin K-dependent carboxylation
• Prothrombin and several other proteins of
the blood clotting system (Factors VII, IX and
X, and
• proteins C and S)
• Two proteins are present in bone that
contain γ-carboxyglutamate, osteocalcin
and bone matrix Gla protein.(fetal warfarin
syndrome= fetal bone abnormalities)

31. Conditions predisposing to a
vitamin K deficiency

32. Vitamin ‘A’

33. Three forms
retinol (Vitamin A alcohol),
retinal (Vitamin A aldehyde)
and retinoic acid (Vitamin A acid).
They are referred as retinoids
Provitamin A: β-carotene (orange to purple)

34. Inter conversion
• Retinal and retinoic acid are formed from
retinol.
• Further retinal and retinol are inter
convertible.
• But retinoic acid cannot be converted to
either retinal or retinol.

35. function
•vision,
•reproduction,
•growth, and
•maintenance of epithelial
tissues.

36. β-Carotene
• Plant foods contain β-carotene,
• can be oxidatively cleaved in the intestine
to yield two molecules of retinal.
• In humans, the conversion is inefficient, and
• the vitamin A activity of β-carotene is only
about one twelfth(1/12) that of retinol.

37. -Carotene
[O ]2
-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

38. RDA
• Retinol equivalents (RE) rather than
International units(lU)
• Woman= 800 RE
• Man= 1000 RE
• One IU equals = 0.3 mg of retinol
• The requirement increases in growing
children, pregnant women and lactating
mothers

39. Absorption
and
transport
of
vitamin A

41. Vision
In the retina, retinaldehyde + light-sensitive
opsin proteins = rhodopsin (in rods) and iodopsin
(in cones).
Any one cone cell = only one type of opsin and is
sensitive to only one color
In the pigment epithelium of the retina, all-trans-
retinol is isomerized to 11-cis-retinol and oxidized
to 11-cis-retinaldehyde

42. This reacts with a lysine residue in opsin,
forming the holoprotein rhodopsin.
the absorption of light by rhodopsin causes
isomerization of the retinaldehyde from 11-cis
to all-trans, and a conformational change in
opsin.
This results in the release of retinaldehyde
from the protein and the initiation of a nerve
impulse.

43. The formation of the initial excited form of
rhodopsin, bathorhodopsin, occurs within
picoseconds of illumination.
There is then a series of conformational changes
leading to the formation of metarhodopsin II,
which initiates a guanine nucleotide
amplification cascade and then a nerve impulse.

44. Wald's visual cycle

45. Visual cascade and cGMP
• metarhodopsin ll
• transducin is activated by metarhodopsin ll
• On inactive transducin = exchange of GTP for
GDP to active transducin
• Which activates cyclic GMP phosphodiesterase
(PDE)
• This enzyme degrades cyclic GMP in the rod
cells
• Decrease cyclic GMP closes the Na+ channels.

46. • results in hyperpolarization
• excitatory response transmitted through the
neuron network to the visual cortex of the
brain

49. Other
functions of vitamin A
• Retinol and retinoic acid acts like steroid
hormone, regulate protein synthesis and
thus, helps in cell growth and differentiation.
• Prevent keratin synthesis, maintain healthy
epithelial cells
• Retinol and retinoic acid are involved in the
synthesis transferrin.
• Maintain proper immune system
• Cholesterol synthesis requires vitamin A.
• Beta carotene as antioxidant

50. Vitamin A deficiency
• 2-4 months stores
• Night blindness (nyctalopia)
• Xerophthalmia
• In certain areas of conjunctiva, white triangular plaques
known as Bitot's spots
• Growth retardation , impairment in skeletal formation
• Degeneration of germinal epithelium, sterile
• Skin rough and dry

53. Introduction
• Vitamin E (tocopherol) is a Antioxidant
• Essential for normal reproduction
• in many animals, hence known as anti-
sterility vitamin.
• Vitamin E is the name given to a group of
tocopherols and tocotrienols

54. • About eight
• but alfa tocopherols is the most important
• The tocopherols are derivatives of 6-
hydroxy chromane (tocol) ring with
isoprenoid (3 units) side chain.
•The antioxidant property is
due to the chromane ring

55. RDA and sources
• Intake of vitamin E is directly related to the
consumption of polyunsaturated fatty acids
(PUFA).
• Man : 10 mg
• Women: 8mg
• One mg of alfa- tocopherol is equal to 1.5 lU.
• Many vegetable oils are rich sources of
vitamin E., other is liver and egg

56. Deficiency symptoms
• sterility,
• degenerative changes in muscle,
• megaloblastic anaemia
• changes in central Nervous system
• Increased fragility of erythrocyte
•Least toxic vitamin

57. Functions
• antioxidant in cell membranes
• Traps free-radical , By preventing the
peroxidation, it keeps the structural and
functional integrity of all cells.
• Reacts with the lipid peroxide radicals formed
by peroxidation of polyunsaturated fatty
acids.
• Initiation, Propagation and Termination
• RH R.
• R. + O2 ROO.
• ROO. + R’H ROOH + R.’
• R.’ + R. (ROO.) (ROOR’) + R-R .’
• R. (ROO.)+ AH (ROOH) RH + A.

58. Prevention of Lipid peroxidation

59. • Reduces the risk of atherosclerosis by reducing
oxidation of LDL
• Gradual deterioration of ageing process is due
to the cumulative effects of free radicals. Hence
Vitamin E helps in scavenging free radicals.
• Vitamin E also boosts immune response.
• Closely associated with reproductive functions
and prevent sterility (proper maintenance of
germinal epithelium)

60. Deficiency manifestation
• In experimental animals, vitamin E
deficiency results in resorption of fetuses
and testicular atrophy.
• Nerve and muscle membrane damage.
• Premature infants are born with inadequate
reserves of the vitamin.
• The erythrocyte membranes are abnormally
fragile as a result of peroxidation, leading
to hemolytic anemia

61. Hypervitaminosis E
• At doses above 1000 lU per day,
• it may cause tendency to hemorrhage, as it is
a mild anticoagulant.
• Least toxic vitamin

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