Vitamins classification, Fat soluble Vitamins VIT A, D, Antivitamins, Provitamins for AHS, & MLT

Vitamins classification, Fat soluble Vitamins VIT A, D, Antivitamins, Provitamins for AHS and MLT. RGUHS syllabus.
for Important questions for Vitamins please check " Water soluble vitamins Thiamine, Niacin, Pyridoxine, Cobalamine, Folic acid, Ascorbic acid" notes

1. FAT SOLUBLE
VITAMINS

2. VITAMINS
Vitamins are organic compounds that are
required in small amounts for normal growth
and metabolism which generally cannot be
synthesized in the body and must be supplied
through the diet

3. Classification of vitamins (Based solubility)
Involved in Energy releasing reactions
Involved in Hematopoietic reactions

4. Water soluble vitamins Fat soluble vitamins
Solubility Water soluble Fat soluble
Absorption Simple Along with lipids
Storage No storage (except vitamin B12)Stored in liver
Carrier proteinNo (except vitamin B12) Present
Excretion Excreted Not excreted
Excess intakeNontoxic Toxic
Deficiency Manifests rapidly (except
vitamin B12)
Manifests slowly
Treatment Regular dietary supply Single large dose
Difference between water soluble & fat soluble vitamins

5. Provitamins: are inactive precursors of vitamins that are
converted into active forms in the body
Examples:
Provitamins Vitamins
β-carotene Vitamin A
7 dehydrocholesterolCholecalciferol (D
3)
Ergosterol Ergocalciferol
ergocalciferol (D
2)
Tryphophan NAD

6. Anti-vitamins- are compounds that interfere with utilization of
vitamins in the body
Exert their effects by
1.Destroying vitamins
2.By interfering with its absorption
3.interfering with the formation of active form of the vitamin
4.Competing for the action of vitamin
Ex: Anti-vitamins Vitamins
Thiaminase Thiamine (B1)
Avidin Biotin (B7)
Dicumorol Vitamin K
Methotrexate Folic acid (B9)
Isoniazid Pyridoxine (B6)

7. Fat soluble vitamin
Vitamin -A

8. Introduction
•Vitamin A is fat soluble. The active form is present only
in animal tissues. the pro-vitamin β-carotene is present
in plant tissues.
•β-carotene is inactive form of vitamin A.
Chemistry
•Vitamin A contains β-ionone ring and isoprenoid side
chains with four double bonds.

9. Vitamin A occurs in two forms in food – namely
retinoids and carotenes
Retinoids are active form of vitamin A, occur in three
forms
i.Retinol – an alcohol
ii.Retinal – an aldehyde
iii.Retinoic acid – an oxidized form
Carotenes are the inactive provitamin form of vitamin A
α- carotene, β-carotene, γ-carotene are the different
types of carotene present in the food

10. RETINOL
RETINAL
RETINOIC ACID
β-ionone ring
4
1
6
11
1
6
11

11. Rich sources : fish liver oils (cod liver oil and shark liver
oil)
Animal sources: milk, butter, cream, cheese, egg yolk,
and liver
Good sources: Vegetable sources- Papaya, Mango,
Pumpkins, Green leafy vegetables like spinach, amaranth

12. The daily requirement of
vitamin A is expressed as
retinol equivalents [RE]
1 retinol equivalent = 1 µg
of retinol or 6 µg of beta
carotene
1 IU = 0.3 mg of retinol
Children = 400-600 µg/day
Men = 750-1000 µg/day
Women = 750-800 µg/day
Pregnancy = 1000 µg/day

13. Absorption, Transport Storage and uptake by tissues
•Vitamin A and its precursors carotene are absorbed in the small intestine
•Dietary vitamin A mainly exists in ester form which is hydrolysed by
cholesterol esterase into fatty acid and free retinol
•Free retinol is absorbed and undergoes resterification in the intestinal
epithelial cells
•It is stored in the liver as retinyl ester, normally as retinyl palmitate.
•One molecule of Vitamin A bind to one molecule of retinol binding
protein(RBP) and transported from liver to peripherical tissues as trans-
retinol.
•The retinol-RBP complex binds to specific receptors on the retina, skin,
gonads and other tissues.
•Then retinol released from RBP and oxidized to retinoic acid and binds to
cellular retinoic acid binding protein (CRBP), and finally to hormone
responsive elements (HRE) of DNA, thus genes are activated.

15. Functions of vitamin A
•The active forms of Vitamin A are Retinol, Retinal &
Retinoic acid.
•Retinol is involved in reproductive function, glycoprotein
synthesis and maintenance of epithelial integrity.
•Retinal – involved in vision.
•Retinoic acid – is an important regulator of gene expression
and is involved in processes of growth and differentiation.
•Carotenoids –which is an inactive and provitamin form of
Vitamin A acts as antioxidant. It has protective effect against
coronary heart disease, anticancer activity and also prevents
senile cataract formation
•Role in Bone and Teeth Formation

16. •Retinal turns visual light into nerve signals in retina of
eye in visual system is known as Wald’s visual cycle.
•The retina of the eye consists of two types of receptor
cells- rods and cones.
•Rods are involved in dim light or night vision whereas
Cones are responsible for bright light and colour vision.
•Rhodopsin (mol. wt. 35,000) is a conjugated protein
present in rods. It contains 11-cis retinal and the protein
opsin.
Role in Vision

17. Structure of Retina (Rods & Cones)

18. Wald's visual cycle / Rhodopsin cycle/ Vitamin A cycle
Rhodopsin cycle comprises two distinct events
✓Bleaching of rhodopsin & generation of nerve impulse
✓Regeneration of rhodopsin by Wald's visual cycle
Bleaching of rhodopsin & generation of nerve impulse:
•When light falls on the retina, photon (from light) is
absorbed by rhodopsin leads to conformational change
and meta rhodopsin II is produced as intermediate and
11-cis-retinal is isomerized to all-trans-retinal and
Opsin.
•Metarhodopsin II activates transducin which intern
activates cGMP phosphodiesterase.

19. •This enzyme degrades cGMP levels in rod cells and
lowers cGMP levels causing closing of Na+ channels .
•This results in hyperpolarization and responsible for
generation of nerve impulses transmitted through
neuron network to visual cortex of the brain and
visualization of light.

21. Wald's visual cycle / Rhodopsin cycle/ Vitamin A cycle
✓Regeneration of rhodopsin through Wald's visual cycle

22. •When light falls on the retinal, 11-cis-retinal is isomerized to
all-trans-retinal and rhodopsin is converted to active rhodopsin
called as meta rhodopsin II.
•All-trans-retinal is converted to all-trans-retinol by reductase in
the outer segment of the rod cells
•All-trans-retinol is transported into the pigment epithelium
where it is converted to 11-cis-retinol by isomerase.
•11-cis-retinol is then converted to 11-cis-retinal and transported
back into the outer segment of the rod. 11-cis-retinal recombines
with opsin to from rhodopsin and the cycle begins again.

23. Dark adaptation time
•The time taken for regeneration of rhodopsin is known as dark
adaptation time.
•Adaptation to the dark is a function of photo-receptor cells in
the retina known as rods.
•Rods contain a photosensitive pigment called rhodopsin.
•It is common experience when a person shifts from bright light
to dark, there is difficulty in seeing & after few minutes
rhodopsin is resynthesized.
•Dark adaptation time depends on the person’s Vit A status & it
is prolonged in Vit A deficiency.

24. Colour vision:
•Cones: Specialized for bright and
color vision.
•Color sensitive Pigments: Red
(porphyropsin), green (iodopsin),
and blue (cyanopsin). All these
pigments are retinalopsin
complexes.
•Visual cycle comparable to that
present in rods is also seen in
cones.
CONES
Porphyropsin
Iodopsin
Cynopsin

25. •When bright light strikes the retina, these pigments are bleached to
all-trans-retinal and opsin, and this reaction passes on a nerve
impulse to brain as a specific colour—red when porphyropsin
splits, green when iodopsin splits or blue for cyanopsin
(Trichromatic).
•Splitting of these three pigments in different proportions results in
the perception of different colours by the brain.

26. •Night blindness or Nyctalopia- earlier manifestation of vitamin A
and it is impaired vision in the dark
•Xerophthalmia- is dryness of conjunctiva and cornea resulting
from progressive keratinization of conjunctiva and cornea
•Bitot spots- are nothing but white plaques present in conjunctiva
•Keratomalacia- is softening of cornea caused by ulceration and
necrosis of cornea which leads to perforation of cornea and
endopthalmitis and blindness
•Anemia- Microcytic hypochromic anemia may be seen
•Hyperkeratanization of skin- skin appears dry and resembles
toad skin
Deficiency manifestations of vitamin A

27. •Keratinization of respiratory, genitourinary tracts
•Decreased mucous secretion & increased infections
•Growth retardation
•Bone thickening and abnormal remodelling

28. Dryness of conjunctiva and cornea
thick & wrinkled
loses mucosal cells – dull, hazy
Keratomalacia Xerophthalmia
Ulceration and necrosis of cornea

29. Bitot’s spot Bitot’s spot
Triangular, white patches

30. Follicular Hyperkeratosis /
phrynoderma

31. Laboratory findings of vitamin A deficiency
1.Impaired dark adaptation of test
2.Decreased vitamin A levels in in plasma
3.Decreased retinol binding protein (RBP) in plasma

32. Vitamin-A Toxicity
Causes:
Over ingestion of vitamin A for prolonged time.
Very high doses of vitamin A
Features:
•Bone and joint pain
•Anorexia (lack or loss of appetite for food)
•Hair loss
•Headache
•Hepatomegaly (enlargement of liver)
•Weight loss

33. VITAMIN D

34. Chemistry of vitamin D
•Vitamin D is a sterol which contains
cyclopentanoperhydrophenantherene ring (CPPP ring)
•Vitamin D in the diet occurs in two forms: Cholecalciferol
(Vitamin D
3) & Ergocalciferol (Vitamin D
2 )
–Cholecalciferol – in Plants
–Ergocalciferol – in Animal tissues
Provitamins of vitamin D:
7 dehydrocholesterol- Vitamin D
3 present in skin
Ergosterol – Vitamin D
2 present in plants

35. RDA:
Children, Pregnancy, lactation = 200–400 IU /day or
(10µg/day)
Adults = 200 IU/day (5 µg/day)
<60 yrs = 600 IU/day
(1 microgram of vitamin D = 40 International Units)
Sources: Good sources: Animal liver, fish liver oil, egg
yolk, milk and dairy products
➢The body it self makes vitamin D when it is exposed to
sun by converting 7 dehydrocholesterol to
cholecalciferol (D3) by photolysis.

36. Synthesis of cholecalciferol ( vitamin D3) in the skin

37. •Vitamin D is absorbed from small intestine through
the formation of mixed micelles by combining with
bile salts and absorption occurs by passive transport
and it is transported from intestine to the liver by
binding with vitamin D binding globulin.
Absorption, Transport Storage and uptake by
tissues

38. Calcitriol or 1,25-dihydroxy cholecalciferol is the active form of
vitamin D
Synthesis of active form of vitamin D or Calcitriol:
The active form of Vitamin- D is Calcitriol (1,25 DHCC). It is
synthesized from cholecalciferol in the liver and kidney.
Cholecalciferol
25 hydroxylase
25-hydroxy cholecalciferol
In Liver
1,25-dihydroxy cholecalciferol
(Calcitriol)
α-hydroxylase (in kidney)
+ PTH

39. Activation of vitamin D
+ PTH

40. Functions of vit D or Calcitriol:
It regulates the plasma levels of calcium and phosphorous
(homeostasis of calcium and phosphorous) by acting on
3 target organs- intestine, bone and kidneys.
•Action on intestine- calcitriol promotes the intestinal
absorption of calcium and phosphorus. In the intestinal
mucosal cell calcitriol binds to the receptor, the
calcitriol-receptor complex then enters into the nucleus
and interacts with DNA, resulting in expression of gene
leading to synthesis of calbindin, which promotes
calcium uptake across the intestinal membrane.

41. •Action on bone- Calcitriol increases blood calcium
level by promoting the mineralization of bone by
deposition of calcium and phosphorus.
•Action on kidney- increases blood calcium levels by
increasing the reabsorption of calcium and phosphorous
from the kidney and by decreasing the excretion of
calcium.
•Along with PTH calcitriol stimulates mobilization of
calcium and phosphorous from bones by stimulation the
synthesis of osteocalcin and there by increases blood
calcium and phosphorous.

42. Plasma calcium ↓
Parathyroid Hormone ↑
Calcitriol ↑
Intestinal Ca
Absorption ↑
Renal Ca
absorption ↑
Bone Ca
Mobilization ↑
Plasma Ca levels ↑
•Other function of includes immune response, beneficial to steroid
resistant asthma patients and Pancreatic cells require for their
function

43. Regulation of vitamin D synthesis
•Its own concentration—by feedback inhibition of
1α-hydroxylase
•Parathyroid hormone (PTH)
•Serum phosphate level
•Serum calcium levels: Hypocalcaemia leads to
marked increase in 1,α-hydroxylase activity, the
effect requires PTH.
•Reduced PTH levels induce synthesis of
24,25-dihydroxy D3

44. Regulation
•Its own concentration—by feedback inhibition of 1α-hydroxylase
•parathyroid hormone (PTH)
•serum phosphate level
•serum calcium levels: Hypocalcaemia leads to marked increase in
1 α-hydroxylase activity, the effect requires PTH

45. Causes for Vitamin D deficiency
•Inadequate supply
•Impaired absorption
•Impaired production of 25 hydroxy vitamin D
3
•Impaired production of 1,25 dihydroxy vitamin D
3
•Resistant to the effects of 1,25 dihydroxy vitamin D
3

46. VITAMIN D –NORMAL VALUE IN SERUM
Optimal concentration : > 30ng/mL
Insufficient : 20 – 29ng/ mL
Deficient : 10-19 ng/ mL
Severe deficiency : 10 ng/mL

47. Deficiency of vitamin D leads to:
Rickets in Children & Osteomalacia in Adults
Rickets: Deficiency vitamin D in children leads to Rickets.
The classical features of rickets are bone deformities. There is
insufficient mineralization of bone. Bones become soft and
pliable. The bone growth is markedly affected. Weight bearing
bones are bent.
The clinical manifestations include bow legs, knock-knee,
rickety rosary, bossing of frontal bones, and pigeon chest.
Plasma calcium and phosphorus are low normal with alkaline
phosphatase (bone isoenzyme) being markedly elevated.

48. An enlargement of the epiphysis at the lower end of ribs
and costochondral junction leads to beading of ribs or
rickety rosary.
Harrison's sulcus is a transverse depression passing
outwards from the costal cartilage to axilla. This is due to
the indentation of lower ribs at the site of the attachment of
diaphragm.

49. Frontal bossing
Bowed legs – Characteristic of
rickets

50. Rachitic rosary: Beaded ribs –
Characteristic of rickets

51. Pegion chest

52. Harrison’s Sulcus

53. Different Types of Rickets
i.The classical vitamin D deficiency rickets; can be cured by giving vitamin D
in the diet.
ii.Hypophosphatemic rickets; mainly due to defective renal tubular
reabsorption of phosphate. Supplementation of vitamin D along with phosphate
is found to be useful.
iii.Vitamin D resistant rickets is found to be associated with Fanconi
syndrome, where the renal tubular reabsorption of bicarbonate, phosphate,
glucose and amino acids are also deficient.
iv.Renal rickets: In kidney diseases, even if vitamin D is available, calcitriol is
not synthesized. These cases will respond to administration of calcitriol.
v.End organ refractoriness to 1,25-DHCC will also lead to rickets. Either a
decrease in the number of cytosolic receptor or a structurally abnormal receptor
is noticed. The bone disease has been found to respond to mega doses of
calcitriol (35 mg/day).

54. Osteomalacia – it is due to deficiency of vitamin D in adults
Causes
–Inadequate exposure to sunlight
–Inadequate dietary intake
Features
•Osteoporosis & Demineralization occurs mainly in spine, pelvis
and lower extremities
•Increased softness & susceptibility to fracture
•Bowing of long bones
Biochemical changes:
•Calcium Reduced, Phosphate reduced, Alkaline Phosphatase
increased, Urinary excretion of calcium diminished

55. OSTEOMALACIA

56. •Increased risk of hypertension
•Impaired synthesis and secretion of insulin
•Insulin resistance
•Glucose intolerance
•Type 2 diabetes mellitus
•Metabolic syndrome
•Obesity
•Myocardial infarction
•Stroke
•Peripheral vascular disease
•Asthma
Other vitamin D deficiencies manifestations

57. References:
1.Vasudevan DM, Sreekumari S, Vaidyanathan K. Textbook of
biochemistry for medical students. JP Medical Ltd; 2013.
2.Satyanarayana U. Biochemistry. Elsevier Health Sciences;
2013 Jun 15.
3.Krishnananda Prabhu. Jeevan K Shetty. Quick Review of
Biochemistry for Undergraduates. Jaypee Brothers Medical;
2014.
4.Harper’s Illustrated Biochemistry, 26th ed. 2003.
5.Google images
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