Vitamins A, D, E, K by Dr. Anurag Yadav

Biochemistry of Fat soluble vitamins - A, D, E, K.
Introduction, source, function, deficiency manifestation and treatment.

1. VITAMINS
MNR MEDICAL COLLEGE & HOSPITAL
Dr Anurag Yadav
MBBS, MD
Assistant Professor
Department of Biochemistry
Instagram page –biochem365
YouTube –Dr Biochem365
Email: [email protected]

2. Vitamins
May be defined as organic compounds
required in small quantities necessary for
growth and maintenance of good health in
human beings

3. Classification
Fat soluble vitamins
Fat soluble
Along with lipids ,
requires bile salts
Carrier proteins present
Stored in liver
Not excreted
Deficiency manifests
only when stores are
depleted
Water soluble vitamins
Water soluble
Simple absorption
No carrier proteins
No storage
Excreted
Manifested rapidly as
there is no storage

4. Hypervitaminosis may
result
Unlikely since vitamins
are excreted

5. VITAMIN A

6. VITAMIN A –structure
Six membered ring with 11 carbon
containing side chain

7. Chemistry
Provitamin form is –beta carotene (HAS
2 MOLECULES OF RETINAL )
Biologically active forms
Retinal
Retinol
Retinoic acid
Its heat stable and light sensitive

8. Vitamin A
Sources
Animal sources –fish
liver oils,
Vegetable and animal
sources –carrot,
papaya , peach ,
tomatoes (red and
yellow)
Palm oil is rich in
carotenoids

9. ABSORPTION
BETA CAROTENE is cleaved in the lumen
of intestine to retinal (beta carotene
dioxygenase)
Retinal is reduced to retinol by retinal
aldehyde dehydrogenase
This is then incorporated in to
chylomicrons and stored in liver
Retinol is transported from liver to other
sites by (RBP)retinol binding protein
in other tissues its bound to CRBP

10. Biochemical functions
1. Vision-WALDS VISUAL CYCLE
rods(for vision in dim light ) and
cones(colour vision)
Pigment in rods-rhodopsin or visual purple
In cones-porphyropsin
iodopsin
cyanopsin

12. 2. Antioxidant properties protect against
cancer and heart disease
3.Maintenace of normal epithelium and skin
4. Metabollic role-Glycoprotein synthesis for
mucous secretions
Biosynthesis of cholestrol
Controls gluconeogenesis in liver
5. normal reproduction
6. retinoic acid for Growth and
differentiation

14. REQUIREMENT
1000 μg/day
1 RE= 1MICROGRAM OF RETINOL

15. Causes of deficiency
Impaired absorption of lipids
Impaired storage in liver disease
Failure to synthesize RBP
Deficiency of particular enzymes
Decreased intake

16. Deficiency manifestations
Manifestations
Early symptoms
Night blindness
Xerophthalmia
Later as disease progresses
Bitot’s spots
Keratomalacia –affects retina
Conjunctival xerosis
Skin and mucous membrane lesions
Failure of skeletal growth

17. Skin diseases
Abnormalities of reproduction

18. Hypervitaminosis–,HAIR LOSS
BONE PAIN
HEADACHE
PEELING OF SKIN
HEPATOMEGALY
NAUSEA, VOMITING

19. Therapeutic use of vitamin A-
1. REDUCES COMLICATIONS OF MEASLES
2. PRECANCEROUS LESIONS RESPOND TO
CAROTENOIDS
3.AS TOPICAL CREAMS

20. VITAMIN D
(CHOLECALCIFEROL)

21. VIT D is also called CALCIFEROLdue to
role in Ca metabolism
Also called ANTIRACHITIC FACTOR as it
prevents rickets
Also called sunshine vitamin

22. STRUCTURE
NATURALLY PRODUCED VIT D 3 -
CHOLECALCIFEROL
LAB SYNTHESISED VIT D 2 -
ERGOCALCIFEROL

23. cholesterol
7 -
dehydrocholesterol
Cholecaiciferol
VitD3
Ergosterol
From plant
Ergocalciferol
VitD2

25. Vitamin D
Sources
Exposure to sunlight
Fish liver oil, fish, egg yolk
RDA
Pre-school children –400 IU
Children and adults –200 IU
Pregnancy and lactation –400 IU
Old age –600 IU

26. ABSORPTION
Skin liver
Circulated in blood bound to vit d binding
proteins synthesized by liver
Dietary vit d is absorbed from duodenum
along with lipids
Carried by plasma as a constituent of
chylomicrons
Taken to liver as chylomicron remnants
Cholecalciferol-PROHORMONE

27. ACTIVE FORM
1:25 DIHYDROCHOLECALCIFEROL
Steps in synthesis
vit D 3
MIT of liver
25 hydroxycholecalciferol kidney
1αHYDROXYLASE 24 HYDROXYLASE
1:25 dihydrocholecalciferol 24:25
dihydrocholecalciferol

28. REGULATION OF ACT VIT D
ACTIVITY OF 1αHYDROXYLASE IS
REGULATED BY
1.PARATHYROID HORMONE
2.PLASMA Ca
3.Insulin ,GH estrogen increase synof activated
form
INHIBITOR OF 1αHYDROXYLASE IS THE
ACTIVE FORM OF VIT D

29. Formation of vitamin D

30. Biochemical functions
CALCITRIOL
INTESTINE BONES KIDNEY
↑CALCIUM AND
PHOSPHORUS
ABSORPTION
INCREASES
MINERALISATION
OF BONES
↑CALCIUM AND
PHOSPHORUS
REABSORPTION

31. OTHER FUNCTIONS
CELL GROWTH AND DIFFERENTIATION
OF
IMMUNOREGULATORY CELLS
EPIDERMAL CELLS
MALIGNANT TUMOUR CELLS
ACTIVE FORM OF VIT D DEPRESSES
IMMUNE SYSTEM

32. Vitamin D deficiency
Causes
No exposure to sunlight
Secondary to malabsorption of vitamin
Secondary to abnormality of vitamin D
activation
Secondary to abnormalities in renal
absorption of phosphates

33. Clinical features
Rickets –in
children
Bone deformities
Knock knee
Bow legs
Frontal bossing
Ricketic rossary
Harissons sulcus
Pigeon chest

35. Osteomalacia -in adults
Bonepain
Bone fracture
osteoporosis
Biochemical parameters
Slight decrease in calcium and phosphorus
Serum alkaline phosphatase increased

36. Different types of rickets
Vitamin D deficiency rickets-
Vitamin D resistant rickets
Hypophosphatemic rickets
Renal rickets

37. Hypervitaminosis D
>1500 IU for long periods
Clinical features
Weakness
Polyuria
Polydipsia
Difficulty in speaking
Confusion
Weight loss
Hypercalcemia,hypokalemia,metabolic alkalosis
Calcification of soft tissues in vascular and renal
tissues

38. VITAMIN E

39. STRUCTURE
Chromane ring /
tocol with an
isoprenoid side
chain
TOCOPHEROL-αβγδ
OF WHICH ALPHA IS
MOST POTENT

40. Sources
Vegetable oils-
RICH SOURCES-
CORN AND SOYA
OIL
GOOD SOURCES -
PALM OIL
OLIVE AND
COCONUT OIL ARE
RELATIVELY POOR

41. Vitamin E
RDA
Males –10mg
Females –8mg
Pregnancy –10mg
Lactation –12mg
>60years –12mg

42. ABSORPTION
Absorbed from the
small intestine
along with lipids
Incorporated into
chylomicrons and
delivered to tissues
Then taken to liver
in the form of
chylomicron
remnants
From liver
exported to target
tissues in the form
of VLDL

43. Biochemical role
Most powerful antioxidant
Reduces the risk of MI by reducing
oxidation of LDL
Slows progression in Alzheimer’s disease
Boosts immune response
Protects erythrocyte membrane from
oxidants
Hypervitaminosis > 1000 IU
Tendency to haemorrhage

45. DEFICIENCY
ITS RARE
FEATURES
1.HAEMOLYTIC ANAEMIA
2.Neuropathy
premature infants with low birth weight are
most commonly deficient.

46. VITAMIN K

47. STRUCTURE
1.VITAMIN K 1(PHYLLOQUINONE) from
plants
2.VITAMIN K 2(MENAQUINONE) syn by
microorganisms
3.VITAMIN K 3(MENADIONE) -
SYNTHESIZED FORM

48. Vitamin K
Sources
Green leafy
vegetables
Intestinal bacterial
synthesis
RDA
50-100mg/day

49. Chemistry
Naphthoquinone derivatives,with a long
isoprenoid side chain.
Absorption and storage
Bile salts are required for normal
absorption and are stored in liver.

50. Biochemical
functions
Coagulation –
required for the
activation of
clotting factors
II,VII,IX,X.They
undergo post
translational
modification.
Functional activity of
C reactive protein,
osteocalcin and
structural proteins of
kidney ,lung,spleen

51. Vitamin K deficiency
Causes
Malabsorption of lipids
Prolonged antibiotic therapy and GI
infections
C/F
Haemorrhagic disease of the new born
In children and adults –bruising
tendency,echymotic patches,mucous
membrane haemorrhage,post traumatic
bleeding,internal bleeding

52. Prolonged prothrombin time and delayed
clotting time
Warfarin and dicoumarol will competitively
inhibit vitamin K
Hypervitaminosis K
Administration of large quantities of
vitamin K
Hemolysis,Hyperbilirubinemia,Kernicterus
and brain damage