2. The Vitamins speak:
“We are for growth, health & welfare of
organisms;
Discharge our duties directly or through
coenzymes;
Deficiency symptoms are our alert signals;
Satisfied we shall be, with additional
supplements.”
Courtesy: Text Book of Biochemistry by U Sathynarayana
3. INTRODUCTION:
‘Vitamine’ nutrient compound required to
prevent nutritional deficiency disease beriberi.
Chemically it was an amine.
Later, number of essential organic nutrients
were discovered.
All of them were not amines.
Therefore, ‘e’ was dropped & the term VITAMIN
is adopted universally & applied to a group of
biologically essential compounds, which
cannot be synthesized by human beings.
4. Since the chemical nature was unknown, letter
designations were applied.
e.g., vitamins A,B,C etc.,
As ‘B’ consisted several substances, the
subscripts were added.
Vitamin B1, B2, B3, B4, B5, B6, B7, B8,
B9,B10,B11,B12 etc.,
(Vitamin B-complex).
some were mixture of already known vitamins.
Vitamin C was identified as pure substance &
named as ascorbic acid.
5. DEFINITION
Vitamins are organic nutrients required in
small quantities for a number of
biochemical functions.
Generally not synthesized by the body.
Supplied through the diet.
However, some vitamins are synthesized
by intestinal microorganisms (e.g., vitamin
K & Biotin)
Insufficient to meet our needs.
7. classification
Vitamins are grouped into two categories based on
their solubility.
1. Fat soluble vitamins
E.g.., Vitamin A, D, E, and K.
2. Water soluble vitamins
E.g., Thiamine(B1), Riboflavin (B2), Niacin (B3),
Pantothenic acid (B5), Pyrodoxine (B6),
Biotin(B7), Folic acid(B9), Cobalamine (B12) and
Vitamin C or ascorbic acid.
8. difference
Water soluble vitamins Fat soluble vitamins
Precursors for
coenzymes &
antioxidants
Coenzymes, hormones
& antioxidants
Non-toxic, excess
amounts are excreted
through urine.
Toxic, lethal in excess as
they are not readily
excreted in urine.
Not stored in the body
(except vitamin B12).
Stored in the body
(liver & adipose tissue)
11. CHEMISTRY:
• Vitamin A is fat soluble.
• Its active form present in animal tissue.
• Its provitamin, beta carotene is present in
plants.
• All the compounds with vitamin A activity are
referred to as retinoids.
• Retinoids are polyisoprenoid compounds
having beta-ionone ring attached to long
hydrocarbon side chain with alternating double
bond.
12. • Three different compounds with vitamin A
activity are
Retinal (vit A aldehyde) also called vit A
Retinol (vit A alcohol) also called vit A1
Retinoic acid (vit A acid) oxidized form
• 3-dehydroretinol is called vitamin A2 and is
present in fresh water fish/fish oils.
• Bioloically important compound is 11-cis-
retinal.
13. Three biologically active molecules
(Active forms of vitamin A)
(vitamers)
1.Retinol (vitamin A alcohol)
2.Retinal (vitamin A aldehyde)
3.Retinoic acid (vitamin A acid)
Retinol r/n Retinal oxdn Retinoic acid
(-CH2OH) (-CHO) (-COOH)
14.
15. CAROTENES:
Inactive provitamin form of vitamin A
It occurs in different chemical forms:
• Alpha carotene
• Beta carotene, most common form in the food
• Gamma carotene
16. Absorption Of Vitamin A
• Diet: Retinol is present in the diet as retinyl ester
(retinyl palmitate) along with long chain FAs.
• Hydrolysis: In the intestinal lumen retinyl ester
is hydrolyzed to release free retinol by the
enzyme retinol ester hydrolase, secreted by the
pancreas.
17. • Beta carotene is cleaved by a dioxygenase, to
form retinal. Retinal is reduced to retinol by an
NADH or NADPH dependent retinal reductase
present in intestinal mucosa.
18. • Retinol derived from esters and from the
cleavage and from reduction of carotenes is re-
esterified with long chain FAs in intestinal
mucosal cells. And incorporated in
chylomicrons and transported to liver.
• In the liver stellate cells it is stored as retinol
palmitate.
19. Difference between vitamin A and
carotenes:
-Activity
-Carbon atoms
-Terminal
group
-B ionone ring
-Source
RETINOL
Active form
20
Alcohol group
One
Animal
BETA CAROTENE
Inactive form
40
No terminal group
Two
Plant
20. Storage of vitamin A:
• Vitamin A is mainly stored in the liver.
• Significant amounts present in kidneys,
adrenals, lungs and retina.
• Vitamin A is mainly stored as retinol
palmitate.
21. Transportation:
• Vitamin A is transported from liver to
peripheral tissues as trans-retinol by retinol
binding protein (RBP)
• Retinol binding protein complex further
complex with prealbumin.
• Such molecular aggregates effectively prevents
glomerular filtration of retinol.
22. Uptake by tissues:
• The retinol –RBP complex binds to specific
receptors on the retina, skin, gonads, and other
tissues.
• The RBP does not enter into the cell.
• Inside the cytoplasm of cells, vit binds to
cellular retinoic acid binding protien(CRBP)
and finally to hormone responsive
elements(HRE) of DNA and genes are
activated.
23. Excretion:
• Retinol is excreted as retinoic acid in bile.
• As retinoyl uronides and excretes in urine.
27. 1. Role in vision:
Wald’s visual cycle
Cyclic events occur in the process of vision, known as
rhodopsin cycle or Wald’s visual cycle.
Photoreception in the cycle is due to functioning of rod &
cone cells present in the retina.
Rhodopsin, a membrane conjugated protein in rod cells
of retina.
11-cis retinal + opsin, a protein (photosensitive
pigment).
Play an important role in vision in dim light.
Upon exposure to light, series of photochemical
isomerizations takes place.
28. Vitamin A And
Vision:
• Active form of vitamin A involved in vision is
11-cis retinal.
• Vision and adaptation to dark is the function
of photoreceptor cells in the retina known as
rods.
• Rods contain photosensitive pigment called
rhodopsin.
• Rhodopsin is made up of 11-cis retinal and
opsin (scotopsin)
29.
30.
31. Rods and
cones:
• Retina has 2 types of cells rods and cones
• Each human eye has 120 million rods and 6
million cones
• rods are involved in dim light vision
• Cones are responsible for bright light vision
and color vision
32.
33. Rhodopsin:
• Is a photo labile glycoprotein embedded in
membranes of rods or cones
• Also called visual purple
• It contains 11-cis retinal and opsin
• Opsins have no light absorbing property
• 11-cis retinal with alternating single and double
bond function as chromophore or light absorbing
group
34. RHODOPSIN CYCLE or VISUAL
CYCLE or WALD CYCLE:
Visual cycle is process where light is
converted to electrical signals in the retina.
Comprises two distinct events:
1. Bleaching of rhodopsin and generation of
nerve impulse.
2. Regeneration of rhodopsin.
37. Regeneration of rhodopsin
Pathway 1
• All trans retinal isomerizes to 11-cis
retinal by the action of retinal isomerase in
the retina.
• 11-cis retinal then combines with opsin to
form rhodopsin.
38. Pathway 2
• All trans retinal is reduced to all trans retinol
by the action of retinal dhydrogenase.
• Followed by isomeriztion of all trans retinol
to 11-cis retinol.
• 11-cis retinol is oxidized to 11-cis retinal by
the action of dehydrogenase.
• 11-cis retinal combines with opsin to form
rhodopsin.
39. Pathway 3
• All trans retinal is reduced to all trans retinol in
the retina.
• All trans retinol reaches liver through
circulation.
• In the liver, all trans retinol is isomerized to 11-
cis retinol.
• 11-cis retinol reaches retina through circulation.
• In the retina 11-cis retinol is oxidized to 11-cis
retinal.
• 11-cis retinal combines with opsin to form
rhodopsin. The cycle repeats.
40. Dark adaptation mechanism:
The time taken for regeneration of
rhodopsin is known as dark adaptation
time.
When a person shifts suddenly from bright
light to dark light, observe difficulty in
seeing.
e.g., entering a cinema hall.
After a few mins rhodopsin is
resynthesised & vision is improved.
41. Dark adaptation time depends on vit A
status of a person (increased in vit A
deficient individuals).
Deficiency of cis-retinal leads to increase
in dark adaptation time & night blindness.
Humans- one eye contains 120 million
rods, each rod with 120 million rhodopsin
molecules.
Cats, mice & owls contain more rods.
42. 2. Regulation of gene expression:
Retinol acts like a steroid hormone in
controlling the expression of certain genes.
3. Growth & differentiation:
Retinoic acid is involved in many process
of growth & differentiation.
Essential for normal gene expression
during embryonic development.
in a) cell differentiation in spermatogenesis
b) differentiation of epithelial cells.
43. 4. Glycoprotein synthesis: Retinyl phosphate play an
important role in the synthesis of glycoproteins (an
important component of mucus).
lack of mucus secretion leads to drying of epithelial
tissues.
Retinol &/or retinoic acid are involved in the synthesis of
iron transport protein transferrin.
Thus, vit A deficiency can lead to anemia from impaired
transport of iron.
5. Antioxidant role of vitamin A:
β-carotene acts as a scavenger of free radicals in
tissues.
prevents the development of epithelial cancers.
decreases the risk of cardiovascular disease.
44. dietary sources
vitamin A or retinoids are from animal sources
• rich sources: fish liver oils, egg yolk, animal liver,
milk and dairy products
• Vitamin A2 is present in fresh water fishes.
carotenes are from vegetable sources:
• Rich sources: carrots, colored fruits like papaya
and mango, tomatoes , spinach, tubers, sweet
potatoes
45.
46. RDA
Children 400 -600µg/day
Men 750-1000µg/day
Women 750µg/day
Pregnancy 1000µg/day
Lactation 1200µg/day
Adults – Men - 1000 RE (3,500 IU)
Woman – 800 IU
1retinol equivalent =1µg retinol
= 6µg β-carotene per day.
1 IU = 0.3µg of retinol
47. vitamin A deficiency
CAUSES:
• inadequate intake
• impaired absorption
• impaired storage
• Impaired transport
• increased excretion
• severe malnutrition
• alcoholism
48. vitamin A deficiency
eye lesions other lesions
night blindness infections
xeropthalmia toads skin
bitots spots anemia
keratomalacia growth retardation
49. Deficiency manifestations
Since vitamin A is stored in liver, deficiency can
develop only over prolonged periods of
inadequate intake.
• Night blindness or nyctalopia: an early
symptom of deficiency.
Lack of retinal may result in impairment of dark
adaptation.
Inability to see in dim light (poor vision in dim
light).
It is a symptom of several eye diseases.
Individuals suffering from night blindness not only
see poorly at night, but also require some time for
their eyes to adjust from brightly lit areas to dim
ones.
50. 2. Xerophthalmia (dry eyes): due to
severe deficiency of vit A
Dryness of conjunctiva & cornea.
(Since retinoic acid is required for growth
& maintenance of epithelium)
Infection usually sets in resulting in
hemorrhaging of the eye & permanent loss
of vision.
3. Bitot’s spots:
Greyish-white triangular plaques are seen
certain areas of conjunctiva.
51.
52. Bitots spot
• Bitot’s spot greyish white triangular plaques
firmly adherent to the conjunctiva
53. 4. Keratomalacia:
Prolonged xerophthalmia, leads to
keratomalacia (soft & milky appearance of
cornea).
Degeneration of corneal epithelium.
Bacterial infection leads to corneal
ulceration.
Perforation of cornea & total blindness.
56. lab findings in vit A deficiency
• impaired dark adaptation test
• decreased vitamin A levels in plasma
• decreased retinol binding protein in
plasma
• Normal blood level of vitamin A is 25-50
microgram/dL
57. Hypervitaminosis A or Toxicity
Vitamin A accumulates in liver. Excess
intake over prolonged periods can be
toxic.
Symptoms: anorexia, scaly dermatitis,
irritability, headache, drowsiness,
diarrhea, enlargement of liver & spleen.
High concentration of retinol releases
lysosomal enzymes – leads to cellular
death.
58. Causes for vitamin A deficiency
Decreased intake.
Obstructive jaundice – defective
absorption.
Cirrhosis of liver – reduced synthesis of
RBP.
Severe malnutrition – deficiency of amino
acids for RBP synthesis.
Chronic nephrosis – RBP is excreted
through urine.
60. • Vitamin D in diet occurs in two forms
vitamin D2 and vitamin D3
• vitamin D2 or ergocalciferol is found in
plants
• Vitamin D3 or cholecalciferol is found in
animals
• Ergocalciferol differs from cholecalciferol
by having double bond between C22 and
C23 and methyl chain at C24
61. Provitamin forms of vitamin D
• 7-dehydrocholesterol
• Ergosterol
7-dehydrocholesterol is an intermediate
during cholesterol synthesis, provitamin form
of vitamin D3, found in skin
Ergosterol is provitamin form of vitamin D2,
found in plants (ergots and yeast)
62. There are two major forms of vitamin D:
1. Vitamin D2 or ergocalciferol
2. Vitamin D3 or cholecalciferol
Synthesis requires sunlight
63. Formation of vitamin D
• Transformation from provitamin to vitamin
is accomplished by ultraviolet rays.
• Photo-chemical activation and photolysis
results in intramolecular rearrangement.
• Vitamin D is derived either from 7-
dehydrocholesterol or ergosterol by the
action of ultraviolet radiation.
64. • 7-dehydrocholesterol is photolyzed non
enzymatically in the epidermal malphigian
layer by UV rays to form precholecalciferol by
cleavage of bond between C9 and C10 of the
B ring of its sterol nucleus. The ring B opens
to form provitamin, Secosterol
• The cis double bond between C5 and C6
isomerizes to a trans double bond to give rise
vitamin D3
• Ergosterol similarly photolyzes to vitamin D2
65.
66. Synthesis of active form of
vitamin D
• Cholecalciferol is transported to liver where
hydroxylation at 25th position occurs to form 25-
hydroxy cholecalciferol by microsomal mixed
function oxidase called vitamin D3 25- hydroxylase
system which consists P450 reductase and
cytochrome P450 which requires NADPH.
• 25 hydroxy cholecalciferol is either stored in liver,
muscles and adipose tissue or carried by D
binding protein to kidneys, bones and placenta
when required.
• In plasma 25HCC is bound to vitamin D binding
protein, an alpha 2 globulin.
67. Synthesis of active form of
vitamin D
• In the kidney, it is further hydroxylated at
the 1st position to form 1, 25 dihydroxy
cholecalciferol. The 1-alpha hydroxylase is
located in mitochondria of proximal
convoluted tubules.It requires cytochrome
P450 and NADPH.
• Active form of D3 is 1,25dihydroxy
vitamin D3 also called calcitriol
71. Regulation of synthesis of 1,25
DHCC
• Depends on plasma calcium and phosphate, they
control hydroxylation reaction at position 1.
• Low plasma calcium level enhances the
production of parathyroid hormone which in turn
activates 1αhydroxylase
• Rise in serum calcitriol level decreases further
calcitriol production by a feed back inhibition of the
1α-hydroxylase
• Hypocalcemia, hypophosphatemia and increase
parathormone increases 1α-hydroxylase to
enhance the calcitriol formation
72. Calcitriol and calcitonin
• Calcitriol is 1,25 dihydroxy cholecaciferol (DHCC)
• Has three hydroxyl groups at 1, 3 and 25 position
hence called calcitriol
• Calcitriol is active form vitamin D and is steroid
hormone
• Actinomycin D inhibits the action calcitriol
• Calcitriol synthesis is self regulated by feedback
mechanis.
• Calcitonin is peptide hormone released fro thyroid
gland, it decreases blood calcium
73. absorption
• Diet from animal sources contain vitamin
D3 and plant sources contain D2
• Bile salts help in absorption of vitamin D
from duodenum and jejunum by
incorporating it in water soluble micelles.
• Absorption occurs by passive transport
74. transport
• Vitamin D is transported from intestine to
liver by binding to α-1 globulin
• Vitamin D is carried in chylomicron
droplets of lymph through out the body
76. Why vitamin D is considered as a
hormone?
Derived from cholesterol, sterol structure.
It can be synthesized in the body (liver &
kidney).
It is released into circulation.
Synthesized at one place & acts on target organs which
are far away.
Has target organs - Bone, intestine & kidney
Regulates calcium & phosphate metabolism.
Mechanism, of action is like a steroid hormone.
Structure, mode of synthesis & mechanism of action are
similar to hormone.
77. Calcitriol binds to receptor protein–retinoid X
receptor
Translocated to nucleus
Calcitriol-receptor complex binds to vitamin D
response elements on DNA
Transcription of mRNA
Calcium binding protein (CBP)
Increases absorption & reabsorption of calcium in
target organs.
78. Biochemical functions
a) In intestine: intestinal villi cells
Calcitriol increases Calcium & Phosphorous
absorption from the intestine.
Enters the intestinal cells.
Calcitriol binds to a cytoplasmic receptor &
translocated to nucleus.
Calcitriol-receptor complex interacts with DNA &
stimulates transcription of (mRNA) genes that
code for calbindin (a protein for calcium transport).
Synthesis of calcium binding protein (calbindins
& osteocalcin)
Increased availability of CBP leads to increased
absorption of calcium.
79. b) In bone: osteoblasts
Increases mineralization of bones (Proper
calcification) due to increased activity of
osteoblasts.
Calcitriol stimulates osteoblasts which
secrete Alkaline phosphatase.
Local concentration of phosphate level is
increased.
The ionic product of calcium &
phosphorous increases, leading to
mineralisation.
80. c) In kidney: convoluted tubule
Calcitriol increases reabsorption of
calcium & phosphorous in the distal
convoluted tubule.
Therefore, both minerals are
conserved.
81. Dietary sources
• Vitamin D3 derived from animal sources
• Rich sources: fish liver oil and shark liver
oil, egg yolk, animal liver, milk and dairy
products
• Vitamin D2 derived from plant sources,
present in significant amounts in yeasts
and moulds
82.
83. RDA
• Children 10 microgram 400 IU/day
• Adults 5 microgram/day 200 IU/day
• Pregnancy 10 microgram/day
• Lactation 10m microgram/day
• Over 60y of age 600 IU/day
• Vit D requirement is also expressed in
international units
• 1 IU of vitamin D is equivalent to 0.025
microgram of cholecalciferol
• 1 microgram of vit D= 40 IU
84. Vitamin D deficiency
• Inadequate supply
• Impaired absorption
• Impaired production of 25 hydroxy
vitaminD3
• Impaired production of 1,25 hydroxy
vitaminD3
• Resistance to the effects of vitamin D3
85. Inadequate supply of vitamin:
• Low dietary intake such as low intake of
milk
• Lack of sunlight
Impaired absorption:
• Obstructive jaundice
• Small intestinal diseases
86. Impaired production of 25
hydroxy vitamin D3
Impaired production of 25 hydroxy vitamin
D3
• Advanced liver diseases-cirrhosis
• Anticonvulsants like phenobarbital increases
the metabolism of 25 hydroxy vitamin D3
Impaired renal synthesis of 1,25 dihydroxy
vitamin D3
• Renal failure
• Inherited defect of renal 1 α hydroxylase
• hypoparathyroidism
87. Resistance to the effects of 1,25
dihydroxy vitamin D3
• Absent or defective receptors for 1,25
dihydroxy vitamin D3
• Familial hypophosphatemic rickets due to
renal tubular defect in phosphate transport
• Fanconi’s syndrome
88. Clinical features
• Clinical condition of vitamin D deficiency
in children is rickets
• Clinical condition of vitamin D deficiency
in adults is osteomalacia
89. Rickets
• Definition : vitamin D deficiency in
children
• Age: seen in children 4 months to 2 years
• Cause: dietary deficiency and non
exposure to sunlight
• Bone mineralization: defective
mineralization of bone causing
enlargement and softening of bone
90. Features of rickets
• Delayed milestones
• Delayed closure of anterior fontanelle
• Delayed dentition
• Deformities of bones
• Decreased serum calcium levels
• Deformation of muscle – pot belly
91. Deformities of bones in
rickets
• Craniotabes: softening of skull on pressure
• Frontal bossing: prominent forehead
• Rickety rosary: beading of ribs at the
costochondral junction
• Pigeon chest: undue prominence of sternum
• Harrison sulcus: horizontal depression
corresponding to insertion of diaphragm
• Knock knees
• Bowed legs
• Metaphyseal thickening at wrist and ankles
100. Biochemical findings in rickets
• Decreased plasma calcium level, normal
9-11 mg/dL
• Decreased plasma phosphorus level ,
normal 3-4.5mg/dL
• Increased plasma alkaline phosphatase,
normal 30-115 U/L
101. osteomalacia
• Vitamin D deficiency in adults
• Low dietary intake
• Inadequate exposure to sunlight
• Demineralization occurs mainly in spine,
pelvis and lower extremities
• Bowing of long bones due to weight of the
body
• Flattening of pelvic bones may cause
difficulty during labour
102. Toxicity of vitamin D
Can be toxic in high doses.
Most toxic of all vitamins.
More than 1500 units per day for very long periods
cause toxicity.
Symptoms:
a)Weakness
b)Polyuria
c)Loss of appetite
d) Nausea
e)Intense thirst
f) Weight loss etc.,
Hypercalcemia leads to calcification of soft tissues
(vascular & renal tissues).
103. VITAMIN – E
(-tocopherol)
Greek: Tocos – child birth; pheros- to bear;
ol- alcohol
Natural antioxidant.
Essential for normal reproduction in many
animals, hence it is known as anti-sterility
vitamin.
104. chemistry of vitamin E
• chemically known as tocopherol
• pale yellow, viscous oil
• soluble in benzene, chloroform and ether
• heat, acid and alkali labile
• destroyed by oxidizing agents and UV rays
• have chromane nucleus with a phenolic
OH group and a isoprenoid side chain
106. Forms of vitamin E
Four forms of vitamin E
Different tocopherol differ by the position and
number of methyl side chains
•Alpha tocopherol: 5,7,8 methyl tocopherol
•Beta tocopherol: 5,8 methyl tocopherol
•Gamma tocopherol: 7,8 methyl tocopherol
•Delta tocopherol: 8 methyl tocopherol
**Alpha tocopherol is the most active and
predominate form
107. absorption
Form: alpha tocopherol is the most prominent
form in the diet
• It is absorbed with fat needs bile salts. Needs
pancreatic lipase for digestion of fat
Site : upper small intestine after incorporation
into water soluble mixed micelles with bile
salts, bile salts are left behind
• In the mucosal cells incorporated to
chylomicrons
108. Transport
• Dietary vitamin E is incorporated to
chylomicron
• In circulation chylomicron transport vitamin
E to the peripheral tissues or to the liver
• Hepatic vitamin E is incorporated to very
low density lipoprotein
• In circulation VLDL is converted to LDL
• Vitamin E is transported with LDL to
peripheral tissues including adipose tissue
109. Storage of vitamin E
• Mainly stored in liver, adipose tissue and
muscles
• In most of the tissues incorporated to
biological membrane because its affinity to
phospholipids
110. Excretion of vitamin E
• During catabolism of vitamin E the
chromane ring and side chain will get
oxidized and excreted in bile after
conjugation with glucuronic acid
111. Functions of vitamin E
ANTIOXIDANT FUNCTION
• Functions as biological antioxidant
• Prevents lipid peroxidation of biological
membranes
• Prevents lipid peroxidation of vitamin A
• It prevents the peroxidation of poly
unsaturated fatty acids present in
phospholipids of membranes
112. Mechanism of antioxidation
• It blocks the lipid peroxidation chain
• It converts peroxy free radicals to
hydroperoxy radicals by transfer of its
phenolic hydrogen atom to a peroxy free
radicals
• Regeneration of vitamin E: oxidized form
of vitamin E is reduced by its interaction
with vitamin C or reduced glutathione
113. Clinical significance of antioxidant
function of vitamin E
• Vitamin E as an antioxidant is protective
against the development of cancer,
atherosclerosis and aging process
• prevents peroxidative effects of
atmospheric pollutants like O3, H2O2, and
NO2 on membrane lipids of bronchi,
bronchioles and pulmonary alveoli
• protect the RBCs from peroxidative action
of free radicals and prevent anemia
• may prevent muscular dystrophy
114. Dietary sources
• Rich sources :
vegetable oils are
richest sources of
vitamin E like wheat
germ oil, soya bean
oil, sunflower oil and
corn oil.
• hydrogenated
vegetable oils.
• peanuts, almonds,
sweet potatoes.
115. RDA: Males – 10mg/day
Females – 8mg/day
Pregnant & lactating women – 10-12mg/day
*Requirement of vitamin E increases as intake
of PUFAs increases.
1mg=1.5 IU
116. antioxidants
Are those which prevents the oxidation of
biological tissues and control the peroxidation of
lipids by certain free radicals.
They scavenge the free radicals & hence protect
biological proteins, PUFAs, carbohydrates,
Nucleic acids etc., from damage by free radicals.
Eg., 1. Enzyme oxidants (catalases,
peroxidases).
2. Non-enzyme antioxidants (vitamin E,
-carotene, vitamin C)
117. Classification:
I. Based on lipid peroxidation:
a) preventive antioxidants- prevent the
peroxidation of PUFA by free radicals.
eg., catalase & glutathione peroxidase.
b) chain-breaking anti-oxidants-
interfere between the chain reaction
carried by free radical (prevent
elongation phase of lipid peroxidation).
eg., -carotene & vitamin E.
118. Mechanism:
Free radicals contain lone pair of electrons
Attack the double bond present mainly in
lipids.
Cell membrane lipids
Blocked by antioxidants
Peroxidation of cell membrane
119. II. Based on location:
Plasma antioxidants – ceruloplasmin,
transferrin, uric acid.
Cell membrane - tocopherol
Intracellular – glutathione peroxidase,
catalase.
III. Based on action:
Enzyme antioxidants
catalase
2H2O2 2H2O + O2
120. Relationship with selenium
• Selenium is component of glutathione
peroxidase important enzyme that oxidizes
and destroys free radicals
• It compliments the antioxidant effects of
vitamin E and reduces the requirement
of vitamin E in the diet
• Selenium is required for the normal
function of pancrease thus enhancing
absorption of vitamin E
121. deficiency
• Causes
• Premature infants: transfer of maternal
vitamin E occurs during last weeks of
pregnancy
• impaired absorption: abetalipoproteinemia,
obstructive jaundice, celiac sprue
• Genetic vitamin E deficiency: lack of a
protein which transports alpha tocopherol
from hepatocytes to VLDL
122. Clinical features
• Hemolytic anemia seen premature infants.
• In adults increased susceptibility of RBCs to
hemolysis under oxidative stress
• Muscle weakness and proteinuria is seen in
vitamin E deficiency
• Spinocerebellar ataxia increased lipid
peroxidation of nervous tissue because of
vitamin E deficiency associated with ataxia,
weakness, loss of vibratory, touch and
position sense
123. Impaired vision and retinopathy
• Outer rods of retina is rich in PUFA
• Oxidation of PUFA due to absence of
antioxidant vitamin E leads to oxidative
damage in retina
• Vitamin E deficiency in animals causes
muscular dystrophy and reproductive
failure
124. therapeutic uses of vitamin E
Beneficial in
• Atherosclerosis by reducing oxidation of
LDL
• nocturnal muscle cramps
• fibrocystic breast disease
• intermittent claudication
125. Hypervitaminosis E
• Doses above 1000 IU per day causes
hemorrhagic tendency because of its mild
anticoagulant effect
126.
127. Vitamin K
anti-hemorrhagic factor
(a quinone derivative)
“Koagulation vitamin” – ‘K’ abbreviation of
German word.
Naphthoquinone derivatives with long
isoprenoid side chain.
Menadione – structurally similar synthetic
compound having vitamin k activity.
(Water soluble)
Only fat soluble vitamin with coenzyme
function.
128. Sources:
Green leafy vegetables are good
sources; Cabbage, cauliflower,
tomatoes, alfa alfa, spinach
RDA: 50-100mg/day (usually availabe in
a normal diet).
129. structure
There are two naturally occurring forms of vitamin K.
Plants synthesize Phylloquinone, which is also known
as vitamin K1
Bacteria synthesize a range of vitamin K forms using
repeating 5-carbon units in the side chain of the
molecule.
These forms of vitamin K are designated menaquinone-
n (MK-n), where n stands for the number of 5-carbon
units. MK-n are collectively referred to as vitamin K2
Vitamin K3 (menadione) is a synthetic form.
130. Biochemical functions
The only known biological role of vitamin K
is as a cofactor for an enzyme that
catalyzes the carboxylation of the amino
acid, glutamic acid, resulting in its
conversion to gamma-carboxyglutamic
acid (Gla).
Responsible for post-translational
modification of certain blood clotting
factors.
131. Gamma –carboxyglutamic acid residues
are negatively charged & combine with
Ca2+ to form a complex.
Prothrombin – Ca complex binds to the
phospholipids on the membrane surface of
platelets.
Leads to increased conversion of
prothrombin to thrombin.
132. Necessary for coagulation factors II
(prothrombin), VII, IX and X to make up the core
of the coagulation cascade.
Synthesized as inactive precursors called
zymogens in the liver.
Undergo gamma –carboxylation of glutamic acid
residues.
These are the binding sites for calcium ions.
Vitamin K dependent gamma carboxylation is
necessary for the functional activity of
osteocalcin as well as structural proteins of
kidney, lung and spleen.
133. Warfarin is a synthetic analogue of vitamin K &
dicumarol an anticoagulant can inhibit the gamma
carboxylation system due to their structural similarity
with vitamin K.
Widely used as anticoagulants for therapeutic
purposes.
134. Deficiency manifestations
Deficiency is uncommon.
Present in diet in sufficient quantity or is
adequately synthesized by the intestinal
bacteria.
Vitamin K deficiency results in impaired blood
clotting & clotting time is increased.
(due to lack of active prothrombin in the
circulation).
Deficiency is seen in newborns due to their
sterile intestine particularly in premature
infants.
135. Causes for deficiency
Malabsorptions of lipids (due to obstructive jaundice, chronic
panacreatitis, sprue, etc.,)
Prolonged antibiotic therapy & GI infections with diarrhea will
destroy the bacterial flora.
Clinical manifestations;
a) Hemorrhagic disease of new born is attributed to vitamin K
deficiency.
b) Pre-term of infants are given prophylactic dose of vitamin K
(1mg menadione).
c) In Childrens & adults , it is manifested as bleeding.
d) Prolongation of prothrombin time & delayed clotting
time are the characteristic of vitamin K deficiency.
136. Toxicity of vitamin K
Administration of large doses of vitamin K
produces hemolytic anemia & jaundice,
particularly in infants.
Toxic effect is due to increased breakdown
of RBC.
*****
Editor's Notes
Retinol ester hydrolase deficiency
Deficiency of mixed micelle bile salt def. obst jaund
Time required to see an object in dim light
Action of phosphate is direct on 1 ahydroxylase whereas calcium is indirect through PTH
