The presentation includes details of fat soluble vitamins: Vitamin A, D, E and K: Chemistry, sources, metabolic role, diseased conditions

1. VITAMINS
Ms. Jigisha Pancholi
Head
Dept. of Biochemistry & Microbiology
IIAPS
Guarat Ayurved University

2. The vitamins are mainly classified into two groups:
1.Fat soluble vitamins are A, D, E, K.
2.Water soluble vitamins are named as B complex and C.
In general, deficiency of vitamins may occur due to:
 Reduced intake
 Impaired absorption
 Impaired metabolism
 Additional requirements
 Increased losses

4. Chemistry
The pro-vitamin, beta-carotene is present in plant tissues.
Beta carotene has two beta ionone rings connected by a
polyprenoid chain.
One molecule of beta carotene can theoretically give rise to two
molecules of vitamin A; but it may produce only one in biological
systems.
All the compounds with vitamin A activity are referred to as
retinoids.
Three different compounds with vitamin A activity are
retinol (vitamin A alcohol)
retinal (vitamin A aldehyde)
retinoic acid (vitamin A acid)

7. Absorption of Vitamin A
Beta carotene is cleaved by a di-oxygenase, to form retinal.
 The retinal is reduced to retinol by an NADH or NADPH dependent
retinal reductase present in the intestinal mucosa.
Intestine is major site of absorption.
The absorption is along with other fats and requires bile salts. In
biliary tract obstruction, vitamin A absorption is reduced.
Within the mucosal cell, the retinol is re-esterified with fatty acids,
incorporated into chylomicrons and transported to liver.
In the liver cells, vitamin is stored as retinol palmitate.

9. Transport from Liver to Tissues
The vitamin A from liver is transported to peripheral tissues as
trans-retinol by the retinol binding protein or RBP.
One molecule of RBP binds one molecule of retinol.

10. Uptake by Tissues
The retinol-RBP complex binds to specific receptors on the retina,
skin, gonads and other tissues.
The RBP does not enter in the cell.
Inside the cytoplasm of cells, vitamin binds to cellular retinoic
acid binding protein (CRBP) and finally to hormone responsive
elements (HRE) of DNA. So, genes are activated.

11. Biochemical Role of Vitamin A
Role in vision
Vitamin A (retinal) is an essential precursor for formation of the
visual pigment, rhodopsin, in the retina of the eye.
Rhodopsin (35,000 D) plays the pivotal role in vision.
It is a membrane protein found in the photoreceptor cells of the
retina.
Rhodopsin is made up of the protein opsin and 11-cis-retinal.
When light falls on the retina, the 11-cis-retinal isomerizes to all-
trans-retinal.

13. Dark Adaption Mechanism
Bright light depletes stores of rhodopsin in rods.
So, when a person shifts suddenly from bright light to a dimly light
area, there is difficulty in seeing.
After a few minutes, rhodopsin is resynthesised and vision is
improved.
This period is called dark adaption time.
 It is increased in vitamin A deficiency.

14. Role in growth
Helps regulate cell development, cell differentiation and
cell division.

15. Role in Bone and teeth formation
Promotes the proper growth of bones and teeth.
Bone cells (osteoblasts and osteoclasts) depend on vitamin A for
their normal functioning.

16. Hair, Skin and Mucous Membrane
Is important in the formation and maintenance of healthy hair,
skin and mucous membranes.
Antioxidant effect
 Carotenoids have Anti-oxidant effect

17. Role in reproduction
 Vitamin A holds an important place in sexual reproduction.
Adequate levels of vitamin A are needed for normal sperm
production.
The female reproductive cycle requires sufficient amounts of
vitamin A.

18. Causes of Vitamin A Deficiency
• Decreased intake
• Obstructive jaundice causing defective absorption
• Cirrhosis of liver leading to reduced synthesis of RBP
• Severe malnutrition, where amino acids are not available for RBP
synthesis
• Chronic nephrosis, where RBP is excreted through urine

19. Deficiency manifestations of Vitamin A
Night Blindness
Visual acuity is diminished in dim light. The patient cannot read or
drive a car in poor light. The dark adaptation time is increased.
Xerophthalmia
The conjunctiva becomes dry, thick and wrinkled.
The conjunctiva gets keratinised and loses its normal transparency.
Dryness spreads to cornea. It becomes glazy and lusterless due to
keratinisation of corneal epithelium.

20. Bitot’s Spots
These are seen as greyish-white triangular plaques firmly adherent
to the conjunctiva.
This is due to increased thickness of conjunctiva in certain areas.

21. Keratomalacia
When the xerophthalmia persists for a long time, it progresses to
keratomalacia (softening of the cornea).
Bacterial infection leads to corneal ulceration, perforation of
cornea and total blindness.

22. Skin and Mucous Membrane Lesions
 Follicular hyperkeratosis or phrynoderma results from
hyperkeratinisation of the epithelium lining the follicles.
The skin becomes rough.
Keratinisation of urinary tract epithelium may lead to urinary calculi.

23. Assessment of Deficiency
Dark adaptation test:- It is the time required to adapt the eye to see
objects in dim light. It is increased in vitamin A deficiency.
RBP level in serum is decreased.
Vitamin A in serum is decreased.
Normal Blood Level of vitamin A is 25 to 50 microgram/dl.

24. Daily Requirement of Vitamin A
The recommended daily allowance (RDA) for
Children = 400-600 microgram/day.
Men = 750-1000 microgram/day
Women = 750 microgram/day
Pregnancy = 1000 microgram/day
One international unit = 0.3 microgram of retinol.

25. Dietary Sources of Vitamin A
Animal sources include milk, butter, cream, cheese, egg yolk and
liver.
Fish liver oils are very rich sources of the vitamin.
Vegetable sources contain the yellow pigment beta carotene. Carrot
contains significant quantity of beta carotene.
Papaya, mango, pumpkins, green leafy vegetables (spinach,
amaranth) are other good sources for vitamin A activity.

26. Hypervitaminosis A or Toxicity
Excessive intake can lead to toxicity since the vitamin is stored.
Symptoms of toxicity include
anorexia
irritability
headache
peeling of skin
drowsiness and vomiting
swelling over long bones
Enlargement of liver is also seen in children

28. Chemical Nature
Also called as tocopherols and anti infertility vitamin.
They have a chromane ring (toco) system, with an
isoprenoid side chain.
There are five naturally occurring tocopherols. Of these,
alpha tocopherol has greatest biological activity.

29. Different types of vitamin E
• Alpha- tocopherol: 5,7,8, trimethyl tocol
• Beta- tocopherol: 5,8 dimethyl tocol
• Gamma- tocopherol: 7,8 dimethyl tocol
• Delta- tocopherol: 8 methyl tocol
• Epsilon- tocopherol
• The alpha tocopherol is the most active and has widest
distribution.

30. Sources of Vitamin E
Vegetable oils are rich sources of vitamin E; e.g.
wheat germ oil, sunflower oil, safflower oil, cotton seed
oil, etc.
Found in fair quantities in dry soya beans, cabbage,
yeast, apple seeds and peanuts.

31. Recommended Daily Allowance
Males 10 mg/day
Females 8 mg/day
Pregnancy 10 mg/day
Lactation 12 mg/day
Or In adult: 20- 25 IU / Day

32. Metabolism of Vitamin E
It is absorbed along with other fats and needs the help of
bile salts.
Tocopherol is absorbed and transported as chylomicrons.
It is stored in adipose tissue.

33. Biochemical role of vitamin E
Vitamin E is the most powerful natural anti-oxidant.
Vitamin E also boosts immune response.

34. • It reduces the risk of atherosclerosis by reducing
oxidation of LDL.
• Vitamin E gives a healthy smooth skin and hair.

35. The free radicals would attack bio-membranes. Vitamin E
protects RBC from hemolysis.
By preventing the peroxidation, it keeps the structural
and functional integrity of all cells.

36. • Vitamin E acts as anti mutagenic and slows the
progression of Alzheimer’s disease.

37. Deficiency manifestation of Vitamin E
In rats, vitamin E deficiency leads to irreversible
degenerative changes in the testes leading to permanent
sterility, motility of sperms is lost and synthesis of sperms is
impaired. In females, the ovary is unaffected but fetus does
not develop and undergoes death.
Human deficiency has not been reported.
But in volunteers, vitamin E deficiency has been shown to
produce increased fragility of RBCs and muscular
dystrophy and weakness.

39. Hypervitaminosis E
At doses above 1000 IU/day, it may cause tendency to
hemorrhage, as it is a mild anti-coagulant.

41. Chemistry
 Calcitriol is the active vitamin D.
Two pro vitamins:
Ergosterol: Provitamin D2 found in plants- not absorbed
well- not of nutritional importance.
7- dehydrocholesterol: Pro vitamin D3 found in the skin.
Formed from cholesterol in the liver, passed into the skin
where it undergoes activation to vitamin D3 by the action of
UV rays.
Inactive to active form done by UV rays.

42. Available in the Malpighian
layer of epidermis.
Breaks
the bond
between 9
and 10
Cis double bond between 5th and
6th carbon atoms, is then
isomerised to a trans double bond
“Sun-shine vitamin”

43. 7 – dehydrocholesterol (precursor of vit.D3)
UV rays
Cholecalciferol
Transported to liver
Hydroxylation at 25th position: 25- hydroxy-cholecalciferol

44. Binds to ‘vitamin D binding protein’
Through blood taken to the kidneys
Hydroxylation at 1st position: 1,25 dihydroxy
cholecalciferol (calcitriol)
Calcitriol is the active form of vitamin D.
The production of vitamin D in the skin is directly
proportional to the exposure to sunlight and inversely
proportional to the pigmentation of skin.

45. Sources of Vitamin D
• Fish liver oil is the richest source.
• Other sources are margarine, butter, cheese, egg yolk,
milk.
• Body can synthesis vitamin D

46. RDA and Absorption
• Adult men: 2.5 ug/ day.
• Absorption and transport: The absorption of vitamin D
is same as the other fat soluble vitamins in the presence
of bile juice and transported with the help of chylomicron.

47. Biochemical Effects of Vitamin D
Vitamin D and Absorption of Calcium
Calcitriol promotes the absorption of calcium from the
intestine.
By increasing the number of calcium binding proteins, the
absorption of calcium from intestine is increased.
Effect of Vitamin D in Renal Tubules
Calcitriol increases the reabsorption of calcium and
phosphorus by renal tubules, so both minerals are conserved.

48. Effect of Vitamin D in Bone
Mineralization of the bone is increased by increasing the
activity of osteoblasts.
Calcitriol co-ordinates the remodelling action of osteoclasts
and osteoblasts.

49. Vitamin D Deficiency
Rickets
Osteomalacia

50. Causes for Vitamin D Deficiency
No exposure of sunlight.
Nutritional deficiency of calcium or phosphate
Malabsorption of vitamin
Abnormality of vitamin D activation: Liver and renal diseases
may retard the hydroxylation reactions.
Deficient renal absorption of phosphates.

51. Rickets
Rickets is seen in children.
There is insufficient mineralization of bone.
Bones become soft.
The classical features of rickets are bone deformities.
Weight bearing bones are bent.

52. The clinical manifestations include
bow legs
knock-knee
rickety rosary
pigeon chest

53. Osteomalacia
The bones are softened due to insufficient mineralization and
increased osteoporosis. Patients are more prone to get
fractures.
Bone aches and pains

54. Hypervitaminosis D
Doses above 1500 units per day for very long periods may
cause toxicity.
Symptoms include weakness, polyuria, intense thirst,
difficulty in speaking, confusion and weight loss.
Hypercalcemia leads to calcification of soft tissues,
especially in vascular and renal tissues.

55. VITAMIN K

56. Chemistry of Vitamin K
They are naphthoquinone derivatives, with a long isoprenoid
side chain.
The length of side chain will differ.
Vitamin K1 has 20C side chain (Phylloquinone). Isolated from
alfa alfa leaves. Also called as mephyton. It is a yellow oil.
Vitamin K2 has a 30C side chain. (Menaquinone).Also known as
fernoquinone.Isolated from putrified fish meal and synthesized by
bacteria. It is a yellow oil.
Synthetic compound having vitamin K activity is Menadione
(Vitamin K3). It is water soluble synthetic vitamin, widely used in
clinical practice.

58. Sources of Vitamin K
• K1: alfa alfa, spinach, cauliflower, cabbage, tomatoes,
soyabeans.
• K2: Synthesized by the bacteria
• RDA: 50-100 mg/day
Absorption
• Absorption is done in the presence of bile.
• It is not stored in any appreciable extent.
• Can cross the placenta and be available to the foetus.
• Not excreted through urine or bile. Faeces contain large
number of quantities.

59. Biochemical Role of Vitamin K
Vitamin K is necessary for coagulation. Factors dependent
on vitamin K are Factor 2 (prothrombin), 7 (SPCA), 9
(Christmas factor) and 10 (Stuart- prower factor).
They undergo post-translational modification: gamma
carboxylation of glutamic acid residues.
These are the binding sites for calcium ions.
The gamma carboxy glutamic acid synthesis requires
vitamin K as a co-factor.

60. Vitamin K dependent gamma carboxylation is also
necessary for the functional activity of osteocalcin as well
as structural proteins of kidney, lung and spleen.

61. Causes for Deficiency of vitamin K
In normal adults dietary deficiency seldom occurs since the
intestinal bacterial synthesis is sufficient to meet the needs of
the body.
 However, deficiency can occur in conditions of malabsorption
of lipids.
 Prolonged antibiotic therapy and gastro-intestinal infections
with diarrhea will destroy the bacterial flora and can also lead
to vitamin K deficiency.

62. Clinical Manifestations of Deficiency
Hemorrhagic disease of the newborn is attributed to vitamin
K deficiency.
The newborns, especially the premature infants have
relative vitamin K deficiency.
This is due to
lack of hepatic stores,
limited oral intake (breast milk has very
low
levels, 15 mg/liter)
absence of intestinal bacterial flora.

63. It is often advised that pre-term infants be given doses of
vitamin K (1 mg Menadione).
In children and adults, Vitamin K deficiency may be
manifested as mucous membrane hemorrhage, post-
traumatic bleeding and internal bleeding.
Prolongation of prothrombin time and delayed clotting
time are characteristic of vitamin K deficiency.

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