VITAMINS (Fat Soluble)

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VITAMINS

Namrata Sharma
PhD(aspirant)
DEFINITION AND CLASSIFICATION
• Vitamins are a group of organic nutrients ,required in
small quantities for a various biochemical functions and
that, generally, cannot be synthesized by the body
and must therefore be supplied in the diet.
VITAMINS

WATER SOLUBLE FAT SOLUBLE


•Vitamin A
•Vitamin D
•Vitamin E
•Vitamin K
Vitamin C B complex

ENERGY RELEASING HEMATOPOIETIC


•VITAMIN Folic acid ,vitamin B 12
B1,B2,B3,B5,B6,B7
WATER SOLUBLE VITAMINS VS FAT SOLUBLE
VITAMINS
FAT SOLUBLE WATER SOLUBLE
•Soluble in fat •Soluble in water

•It can be stored in liver and adipose •Not stored in large amount in body, except
tissue Vit.B12

•They are not readily excreted in urine •They are readily excreted in urine

•Deficiency state develops slowly •Deficiency state develops rapidly and are
multiple

•Excessive consumption leads to toxic •Excessive consumption are usually non toxic
effects

•Function are variable •It forms co-enzyme and participates in


•Vitamin K has co-enzyme function biochemical reactions
SOURCE OF VITAMINS
• Vitamins are mainly obtained from food, but a
few are obtained by other means. For example:
– Microorganisms in the intestine—commonly known as
"gut flora"—produce vitamin K, biotin and
cobalamin.
– Vitamin D can be synthesized in the skin with the
help of the natural ultraviolet wavelength of sunlight.
– Humans can produce some vitamins from precursors
they consume. Examples include vitamin A, produced
from beta carotene, and niacin, from the amino acid
tryptophan.
DEFICIENCY OF VITAMINS
• Because human bodies do not store most vitamins,
humans must consume them regularly to avoid
deficiency.
• The store for different vitamins in human body vary
widely; Vitamins A, D, and B12 are stored in significant
amounts in the human body, mainly in the liver.
• Usually water soluble Vitamins are not stored in the
human body in significant amounts, so deficiencies
occurs early.
• Deficiencies of vitamins are classified as Primary and
Secondary.
DEFICIENCY OF VITAMINS
• A primary deficiency occurs when body does not get
enough of the vitamin from food.
• A secondary deficiency may be due to an underlying
disorder that prevents or limits the absorption or use of
the vitamin, due to a “lifestyle factor”, such as smoking,
excessive alcohol consumption, or the use of
medications that interfere with the metabolism or use of
the vitamin.
• People who eat a varied diet are unlikely to develop a
severe primary vitamin deficiency.
• In much of the developed world, such deficiencies are
rare; this is due to
– An adequate supply of food; and
– The addition of vitamins and minerals to common foods, often
called fortification.
Chemistry of Vitamin A
 Vitamin A has got several
forms -Carotene (precursor, a carotenoid

 Ring structure present in oxidative cleavage

Vitamin A is β ionone ring CH2OH

 Provitamin A, β carotene Retinol (vitamin A)

contain 2 β ionone ring O


CH2O P O
 Cleaved in the intestine by a OH
dioxygenase. Retinol phosphate

The normal serum


11
 C
H
12

concentration of vitamin is 15- O


Retinal
60 mg/100ml (All-trans-retinal) ( 11 -cis-retinal)
C
O H
OH
C
O
Retinoic acid

Figure 4-1 Structure of vitamin A and related compounds


Vitamin A
RETINOIDS
• Retinol , Retinal and Retinoic acid
– Retinal: 11 cis retinal for normal vision
– Retinoic acid: Normal morphogenesis, growth and cell
differentiation
– Retinol: Reproduction.
• Found in animal source
• BETA –CAROTENE ( Provitamin A )
 Found in plant source

 it is cleaved in the intestine to produce two molecule

of retinal
ABSORPTION, TRANSPORT AND BIOCHEMICAL FUNCTION
Diet
INTESTINAL CELL RETINA
Beta carotene Retinyl esters
Beta- carotene All-Trans Retinol
retinol
Retinal All-Trans Retinal

Retinol visual cycle

Retinyl esters
TARGET TISSUE
Retinol

Chylomicron Retinoic acid

Retinol Gene activation


LIVER
All-Trans Retinol
Specific Protein synthesis

Retinyl palmitate Cellular differentiation


(stored)
MECHANISM OF ACTION OF VIT A

• Retinol is oxidized to retinoic acid.


• Retinoic acid binds to specific receptor protein present in
the nucleus of target tissue such as epithelial cells.
• Then, It interacts with gene to regulate retinoid specific
RNA synthesis, resulting in protein synthesis which
mediate different physiological function.
– For example, retinoids, after binding to the receptors,
control the expression of the gene for keratin, a type
of protein, present in skin epithelium.
– They also act as a regulator of steroid and thyroid
hormone and 1,25 dihydroxycholecalciferol (active vit.
D).
FUNCTIONS OF VITAMIN A
• Vitamin A plays a role in a variety of functions
throughout the body, such as:
– Vision
– Maintains epithelial tissue (cornea, skin, mucosa)
– Transcription and involved in cell growth and development.
– Immune function: by maintaining epithelial tissues
– Embryonic development and reproduction:
• Retinol and retinal are essential for normal reproduction, supporting
spermatogenesis in the male.
– Vitamin A also assists in bone growth
– Antioxidant Activity (beta carotene)
VITAMIN A AND WALD’S VISUAL CYCLE

• Vitamin A is a component of visual pigments of rods and cone


cells of retina
• Rhodopsin is a visual pigment of rod , which is made up of
protein OPSIN and 11-CIS RETINAL
• When rhodopsin is exposed to light , a series of
photoisomerization occurs and release All-trans retinal +
opsin
• This process triggers a nerve impulse that is transmitted by
optic nerve to brain
• Regeneration of Rhodopsin requires isomerization of all-trans
Retinal to 11-cis retinal
• Finally , 11-cis retinal + opsin forms Rhodopsin and used for
next cycle
VITAMIN A AND WALD’S VISUAL CYCLE
opsin
11-cis-Retinal
dark

(retina)
isomerase
Rhodopsin

Light
energy

trans-Retinal
nerve
impulse
opsin
DIETARY SOURCES

A) Animal source:.
Liver, Kidney, Egg ,Milk ,Cheese, Butter ,Fish liver oil.
B) Vegetable Sources (beta carotene)
Yellow and dark green vegetables, Fruits like mango ,
papaya, carrots, pumpkins etc.
Recommended dietary allowance (RDA)

• Required Daily Allowance of Vitamin A (μg


of Retinol) (ICMR 2010)
– Children (1–6 yrs) 400 µg/day
– Men 600 µg/day
– Women 600 µg/day
– Pregnancy 800 µg/day
– Lactation 950 µg/day
VITAMIN A DEFICIENCY

A) OCULAR MANIFESTATION
– Ocular Manifestation due to vitamin A deficiency is known as “
XEROPHTHALMIA”
B) EXTRA-OCULAR MANIFESTATIONS
– Growth retardation
– Effect on reproduction
• Sterility in male and termination of pregnancy in female
– Effect on skin and epithelium
• Skin become rough and dry and chance of acne increases
– Epithelium of GIT ,Urinary tract, Respiratory tract are
Keratinized and leads to increased bacterial infection.
– Formation of stone in kidney.
– Increased risk of Heart disease, lung and skin cancer
XEROPTHALMIA
Ocular Manifestation due to vitamin a deficiency is
known as “ XEROPHTHALMIA”.
Bitot's spots
STAGES OF XEROPTHALMIA
XN : Night blindness

XIA :Conjunctival xerosis

XIB : Bitot's spots


Corneal
X2 : Corneal xerosis ulceration

X3A: Corneal ulceration/keratomalacia less


than 1/3 corneal surface.

X3B : Corneal ulceration/keratomalacia equal Corneal scar


to or more than 1/3 corneal surface.

XS : Corneal scar

XF : Xerophthalmia fundus
HYPER VITAMINOSIS A
• Since vitamin A is fat-soluble, disposing of any excesses
taken in through diet is much harder than with water-
soluble vitamins B and C, thus vitamin A toxicity may
result.
• CLINICAL FEATURES:
– Nausea, jaundice, irritability, anorexia, vomiting, blurry vision,
headaches, hair loss, muscle and abdominal pain and
weakness, drowsiness and altered mental status and congenital
anomaly in fetus.
HYPER VITAMINOSIS A

• DOSE RELATED TOXICITY


Acute toxicity generally occurs at doses of 25,000 IU/kg
of body weight, with chronic toxicity occurring at 4,000
IU/kg of body weight daily for 6–15 months.
• NOTE
These toxicities only occur with preformed (retinoid)
vitamin A (such as from liver). The carotenoid forms
(such as beta-carotene as found in carrots), give no such
symptoms, but excessive dietary intake of beta-carotene
can lead to carotenodermia which causes orange-
yellow discoloration of the skin.
INTRODUCTION TO VITAMIN D

• Vitamin D is a fat-soluble Vitamin, the two major forms


of which are vitamin D2 (or ergocalciferol) and vitamin
D3 (or cholecalciferol).
• Vitamin D resembles sterols in structure and function as
hormones.
• Vitamin D is stored in adipocytes and liver.
RDA OF VITAMIN D:
• RDA in adult = 200 to 400 IU of vitamin D.
SOURCE OF VITAMIN D

1) DIET
• The animal source contains vitamin D3 (Cholecalciferol) and Plant
source contains vitamin D2 (Ergocalciferol, but it is not absorbed
well hence, not of nutritional importance)
• Natural sources of vitamin D include;
– Fish liver oils, such as cod liver oil
– Fatty fish species, such as:
• Catfish, Salmon, Sardines, Tuna
– A whole egg ,cheese, milk
– Beef liver
– Fortification of food (milk, butter)
2) ENDOGENOUS VITAMIN PRECURSOR
• 7-Dehydrocholesterol in skin is converted into Cholecalciferol
(vitamin D3 ) after exposure to sunlight.
METABOLISM OF VITAMIN D

25-hydroxylase

known
As
1-alpha-hydroxylase calcitriol

(PTH)
CALCITRIOL

CALCITRIOL RECEPTOR COMPLEX

BONE
FORMATION mRNA

Ca ++ in Ca++
CALCIUM BINDING PROTEIN AND absorption
plasma
CALCIUM ATPase IN INTESTINAL CELL
Absorption, transport and
storage
• Vitamin D is absorbed in the small
intestine for which bile is essential.
• Through lymph, vitamin D enters the
circulation bound to plasma alpha-2
globulin and transported throughout the
body.
• Liver stores small amount of vit D.
FUNCTIONS OF VITAMIN D

1) Maintaining calcium and phosphate


homeostasis:
– Increase intestinal absorption of calcium and phosphate. (By
increasing the synthesis of calcium ATPase).
– Decrease excretion of Calcium and phosphate through kidney.
(or it increases reabsorption of calcium and phosphate from
kidney)
– IN BONE
a) In Osteoblast, it stimulates calcium and phosphate
uptake for deposition of calcium phosphate
(mineralization)
b) Along with parathyroid hormone, it increases mobilization
of calcium and phosphate from bone.
• The main function of Vit D is to increase the serum calcium
and phosphate level.
FUNCTIONS OF VITAMIN D

2) Role in immune function:


– The hormonally active form of vitamin D (calcitriol) mediates
immunological effects by activating immune cell , for e.g:
monocytes, macrophages, T and B cells.
3) Role in cancer prevention and recovery:
– The vitamin D hormone, calcitriol, has been found to induce
death of cancer cells.
4) Role in cardiovascular disease prevention:
– Researches have shown that vitamin D may play a role in
preventing or reversing coronary disease (Angina and
MI).
– Vitamin D deficiency is associated with an increase in high
blood pressure and cardiovascular risk.
VITAMIN D DEFICIENCY
• Deficiency of vitamin D can result from a
number of factors:
– Inadequate intake coupled with inadequate
sunlight exposure.
– Disorders that limit its absorption from the
gastrointestinal tract.
– Conditions that impair conversion of vitamin D into
active metabolites, such as liver or kidney
disorders.
VITAMIN D DEFICIENCY
• Deficiency results in impaired bone mineralization, and
leads to bone softening diseases including:
1) Rickets:
– Rickets is characterized by the continued formation of
the collagen matrix of bone, but incomplete
mineralization, resulting in soft, pliable bones in children.
2) Osteomalacia:
– In osteomalacia, demineralization of preexisting bones
increases their susceptibility to fracture.
– Occurs in adults.
HYPERVITAMINOSIS D

• Vitamin D is most toxic of all vitamins if it is in excessive


amount. Like all fat-soluble vitamins, vitamin D can be
stored in the body.
TOXIC LEVEL
– In adults, sustained intake of 2500 micrograms/day (100,000 IU)
can produce toxicity within a few months.
– For infants ,vitamin D concentrations of 1000 micrograms/day
(40,000 IU) has been shown to produce toxicity within 1 to 4
months.
• Loss of appetite, nausea, thirst, and lethargy can occur.
• Enhanced calcium absorption and bone resorption results in
hypercalcemia, which can lead to deposition of calcium in many
organs, particularly the arteries and kidneys.
VITAMIN K
INTRODUCTION OF VITAMIN K

• Vitamin K is a fat-soluble vitamin.


• The "K" is derived from the German word
"koagulation." Coagulation refers to the process of
blood clot formation.
• FORMS OF VITAMIN K
– There are two naturally occurring forms of vitamin K:
• Phylloquinone: which is also known as vitamin K1. Plants
synthesize it.
• Menaquinone (K2):
– mainly synthesized by bacteria in our gut.
– Also found as animal source.
– Vitamin K3 is synthetic form (menadione).
INTRODUCTION OF VITAMIN K

RDA
– 70 – 140 mg/day for adult
SOURCE
1) DIET:
– Green leafy vegetables like cabbage, spinach,
cauliflower (K1)
– Egg yolk, liver, meat, dairy products. (K2)
2) ALSO PRODUCED BY INTESTINAL BACTERIA
Absorption, transport and
storage
• Vitamin K is taken in the diet or synthesized by
the intestinal bacteria.
• Its absorption takes place along with fat
(chylomicrons) and is dependent on bile salts.
• Vitamin K is transported along with LDL and is
stored mainly in liver and, also in other tissues in
a less amount.
FUNCTIONS OF VITAMIN K

1) Coagulation (clotting)
– The only known biological role of vitamin K is as a cofactor for
an enzyme that is needed for the activation of precursor of
clotting factors II, VII, IX, and X.
2) Bone mineralization
– Three vitamin-K dependent proteins have been isolated in
bone: Osteocalcin, matrix Gla protein (MGP), and protein S.
– The function of these protein are unclear but is thought to be
related to bone mineralization.
ROLE OF VITAMIN K IN COAGULATION
( Act as coenzyme for carboxylation of glutamic acid of
precursors proteins)

CARBOXYLASE
DEFICIENCY OF VITAMIN K
Vitamin K deficiency results in impaired blood clotting,
• Symptoms include easy bruising and bleeding that may
be manifested as nosebleeds, bleeding gums, blood in
the urine, blood in the stool and extremely heavy
menstrual bleeding.
• Adults: Vitamin K deficiency is uncommon in healthy
adults. Adults at risk of vitamin K deficiency include:
– Those taking vitamin K antagonist anticoagulant drugs (eg:
warfarin and Dicumarol)
– Individuals with significant liver disease (clotting factors
are not formed)
– Additionally, individuals with disorders of fat malabsorption
may be at increased risk of vitamin K deficiency (eg: bile
duct obstruction)
DEFICIENCY OF VITAMIN K
• Newborn and infants:
– Vitamin K deficiency in newborns may result in a
bleeding disorder called vitamin K deficiency
bleeding of the newborn, also called hemorrhagic
disease of newborn.
– In infants, vitamin K deficiency may result in life-
threatening bleeding within the cranial cavity
(intracranial hemorrhage).
• Because it is life-threatening and easily prevented, an
injection of phylloquinone (vitamin K1) be
administered to all newborns or oral dose of vitamin k is
given.
HYPERVITAMINOSIS K

• Administration of large dose of vitamin K can


produce HEMOLYTIC ANAEMIA AND
JAUNDICE IN INFANT.
VITAMIN E
• The E vitamins consist of eight naturally
occurring tocopherols, of which α-tocopherol is
the most active.
• RDA
– 8- 10 mg/day
• Chief functions
– Antioxidant:
• Because of this property, it stabilizes cell membranes,
regulates oxidation reactions and protects polyunsaturated
fatty acids in the membrane.
• Role in preventing disease like cardiovascular disease,
cancer and cataract.
VITAMIN E SOURCES
• Vegetable oils are rich
sources of vitamin E
• Whereas liver and eggs
contain moderate
amounts.
Deficiency of vitamin E
• Deficiency symptoms
– Red blood cell rupture (hemolysis)
– Nerve damage
– Sterility
– Degenerative change in muscle
MCQ
Human Milk is deficient in which vitamins?
(A) Vitamin C
(B) Vitamin A
(C) Vitamin B2
(D) Vitamin K
Note:
vit D is present in very less amt. in human
milk
MCQ
• Human Milk is deficient of which mineral?
(A) Phosphorus
(B) Sodium
(C) Iron
(D) Potassium
Note:
Iron is less than cow’s milk but it is absorbed
better
MCQ
• Which of the following vitamins has
greatest Antioxidant properties?
A. vitamin B1
B. vitamin B12
C. vitamin A
D. vitamin E
E. vitamin C
MCQ
• Xerophthalmia occurs with deficiency of:
A. Vitamin A
B. vitamin D
C. vitamin B1
D. vitamin B12
MCQ
• Rickets develops with a lack of:
A. Vitamin A
B. vitamin D
C. vitamin B1
D. vitamin C
• Which vitamin
deficiency is
responsible for the
condition shown in
the picture?
a) Folic acid
b) Cobalamin
c) Vitamin A
d) Vitamin D
• All of the vitamins are synthesized by Gut
flora except:
a) Vit K
b) Biotin
c) Cobalamin
d) Vit D

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