VITAMIN A
By : Aashana Pardeshi
Roll no. : 03
LEARNING OBJECTIVES
• History of vitamin A
• Chemistry of vitamin A
• Daily requirement
• Dietary sources
• Absorption
• Transport and storage
• Biochemical roles
• Disorders
History of vitamin A
• McCollum and Simmonds identified the vitamin A activity in the diet
• Richard Kuhn identified Carotenes
• Paul Karrer elucidated the structure of vitamin A1 in 1931
INTRODUCTION
• Vitamin A is fat soluble that primarily comes from animal sources
as retinol, a retinoid
• The retinoids, a family of structurally related molecules , are
essential for vision , reproduction, growth , and maintenance of
epithelial tissues.
• The also play role in immune functions
CHEMISTRY
• The active form of vitamin A is present only in animal tissue
• Beta-Carotene (pro - vitamin ) is present only in plant tissue . Beta-
carotene has two beta ionone rings connected by polyprenoid chain
• One molecule of beta-carotene can theoretically give rise to 2
molecules of vitamin A
• All-Trans variety of retinal also called Vitamin A1 is most common
• Biologically important compound is 11-cis-retinal
• All compounds with vitamin A activity are called retinoids
• Different compounds with Vitamin A activity are :
RETINOL , RETINAL ,RETINOIC ACID
DAILY REQUIREMENT
• Recommended daily allowance of Vitamin A is measured in terms of
retinol activity equivalent which equal to 1 micrograms of retinol
• Adult men :1000 microgram/day
• Adult women :850 microgram/ day
• Pregnancy : 900 microgram/day
• Lactation : 950 microgram / day
• Children : 400 -650 microgram / day
Dietary sources
• Animal sources : fish liver oils ( cod liver oil and shark liver oil ) are
very rich sources of the vitamin
• Plant sources : vegetable sources containing the yellow pigment
beta carotene
• Carrot contains significant quantity of beta carotene
DIGESTION AND ABSORPTION
• Retinyl esters from animal source are broken down releasing retinol
• Beta carotene from plant sourceis cleaved by dioxegenase , to form
retinal
• The retinal is reduced to reduced to retinol by retinal reductase in
intestinal mucosa
• Upper half of the Intestine is the major site of absorption
• Its absorption is along with other fats and requires bile salts for formation
of micelles
• Within mucosal cells , the retinol is re-esterified with fatty
acid ,Incorporated in chylomicrons and transported to liver where it is
stored as retinol palmitate
TRANSPORT AND UPTAKE
• Vitamin A from liver is transported to peripheral tissue as trans-
retinol by the retinol binding protein (RBP)
• 1 molecule RBP binds 1 molecule of retinol
• In case of vitamin A deficiency RBP level in blood falls
• Inside the cytoplasm of cells, vitamin binds to the cellular retinoic
acid binding protein (CRBP) and finally hormone response elements
of DNA
BIOCHEMICAL ROLE
1. ROLE IN VISION
WALD VISUAL CYCLE
• Wald was awarded Nobel prize for identifying the role of Vitamin A in
vision
• 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
all-trans-retinal
• The photon produces immediate conformational change
• The unstable intermediates are produced :
Rhodopsin > Barthorhodopsin >Lumirhodopsin >Metarhodopsin I
>Metarhodopsin II >opsin + all-trans-retinal
Generation of nerve impulse
• The visual pigments are G – protein coupled receptors and 11-cis-
retinal locks the receptor protein (opsin) in its inactive form
• Transducin is the G protein in retina PHOTOTRANSDUCTION
CASCADE
• During this cascade ,there is huge amplification
1 photon> 1 rhodopsin >500 transducin
• The nerve impulse thus generated in the retina
is transmitted to visual cortex
Regeneration of 11-cis-retinal
• After dissociation ,the opsin remains in retina ; but trans-retinal
enters the blood circulation
• The all-trans-retinal is isomerized to 11-cis-retinal in retina itself in
dark by the enzyme retinal isomerase
• Alternatively, all-trans-retinal is transported to liver and then
reduced All-trans-retinol and further reduced to 11-cis-retinol
• 11-cis-retinol is then oxidised to 11-cis-retinal by ADH which is then
transported to retina
2. Dark Adaptation mechanism
• Bright light depletes stores of rhodopsin in rods
• Therefore, when a person shifts suddenly from bright light to a dimly
lit area , there is difficulty in seeing
• After some time rhodopsin is resynthesized and vision is improved .
This period is called dark adaptation time
• The dark adaptation time is increased in vitamin A deficiency.
CONES FOR COLOR VISION
• Cones are responsible for vision in bright light as well as color vision
• They contain photosensitive protein conopsin
• There are 3 types of cones , each is characterized by a different
conopsin that is maximally sensitive to either blue (cyanopsin),
green (iodopsin), or red (porphyropsin)
• In the cone also , 11-cis-retinal is the chromophore
Gene regulation
• Retinoic acid has role in regulation of gene expression and differentiation
of tissues
• The all-trans-retinoic acid and 9-cis-retinoic acid act like steroidal
hormones. They bind to nuclear receptors ;retinoic acid along with the
receptor binds to the response DNA elements of DNA
• Retinoic acid receptors (RAR) bind all-trans-retinoic acid, while retinoid X
receptors (RXR) bind to 9-cis-retinoic acid. RXRs form dimers with vitamin
D receptor also
• This explains why deficiency of vitamin A impairs vitamin D function,
when there is lack of 9-cis-retinoic acid to form receptor dimers , vitamin
D functions not optimal
Immunological System
• Retinoic acid influences the differentiation of T cells
• In presence of retinoic acid , the dendritic cells located in the gut are
able to mediate the differentiation of T cells into regulatory T cells
• When vitamin A is deficient in the diet ,the population of
haematopoietic stem cell decreases
Reproductive system
• Retinol acts like a steroid hormone in controlling the expression of
certain genes.
• This may account for the requirement of vitamin A for normal
reproduction.
• In vitamin A deficiency, miscarriages are noticed in female rats
• while atrophy of germinal epithelium and sterility are seen in male
rats.
Antioxidant property
• There is a correlation between the occurrence of epithelial cancers
and vitamin A deficiency.
• The anticancer activity has been attributed to the natural antioxidant
property of carotenoids.
• Fresh vegetables containing carotenoids were shown to reduce the
incidence of cancer.
Effect on skin
• Vitamin A is necessary for the maintenance of normal epithelium and
skin
• Retinoic acid appears to maintain normal skin health by switching on
genes and differentiating keratinocytes into mature epidermal cells
Causes of vitamin A deficiency
• Primary deficiency: due to decreased intake ,in those who do not
take adequate intake of carotenoid form fruits and vegetables
• Secondary deficiency: I.Obstructive jaundice causing defective
absorption.
II. Cirrhosis of liver leading to reduced synthesis of RBP
III.Severe malnutrition, where amino acids are not available for RBP
synthesis.
IV.Chronic nephrosis, where RBP is excreted through urine.
DISORDERS
Preventable blindness
• The deficiency of vitamin A is the most common cause of
blindness in Indian children below the age of 5.
• One third of the world’s blind population is residing in India. About
40%
of blindness is preventable.
• Vitamin A deficiency is a major public health problem.
• A single dose of vitamin A is given, as a prophylactic measure, to
children below 1 year age.
2. Night Blindness [ Nyctalpia]
• Nyctalopia refers to night blindness or difficulty of the eye in
visualizing under dim light or at night.
• Daytime vision, however, is unimpaired.
• Nyctalopia is due to the eye's inability to adapt quickly from
lightness to darkness.
• The principle cell-type associated with Nyctalopia is rod cells.
3. Bitot’s spot
• BITOT'S SPOT is a sharply defined, gray or white lesion involving the
exposed portion of the bulbar conjunctiva
• All the occular changes are completely reversible when vitamin is
supplemented
4.Xerophthalmia
• Conjunctiva becomes dry , thick , wrinkled
• Conjunctiva gets kertinized and loses its normal transperancy
5. Keratomalacia
• When the xerophthalmia persists for long time , it progresses to
keratomalacia
• There is degradation of corneal epithelium
Skin and mucus membrane lesions
• Follicular hyperkeratosis or phrynoderma results from
hyperkeratinization of the epithelium lining the follicles. The skin
becomes rough.
• Keratinizing metaplasia of the epithelium of the respiratory,
gastrointestinal and genitourinary tracts have been observed.
• Epithelium is atrophied. Keratinization of urinary tract
epithelium may lead to urinary calculi.
DISORDERS OF
PHOTOTRANSDUCTION
• Bradyopsia : Mutation in transducin activating protein leading to
defective vision with changes in light intensity
• Retinitis pigmentosa : An inherited condition leading to
progressive loss of vision. The number of functional rods and cons
decreases due to degenrative changes
HYPERVITAMINOSIS A [ TOXICITY ]
• Hypervitaminosis A is a condition that occurs when a person has too
much vitamin A in their body.
• This condition may be acute or chronic. Acute toxicity occurs after
consuming large amounts of vitamin A over a short period of time,
typically within a few hours or days.
• Chronic toxicity occurs when large amounts of vitamin A build up in your
body over a long period of time.
• Symptoms include changes to vision, bone pain, and skin changes. Chronic
toxicity can lead to liver damage and increased pressure on your brain.
Assessment of deficiency of vitamin
A
• 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 (retinol binding protein) level in serum is decreased.
• Vitamin A in serum is decreased. The colorimetric measurement is
based on Carr and Price reaction, where retinoids are made to react
with antimony trichloride to give a blue color. Vitamin A may be
directly measured by spectrophotometry; it has maximum
absorption
at 325 nm
• Normal blood level of vitamin A is 25 to 50 mg/dL
Treatment
• When Vitamin A deficiency is identified , supplementation is given as
capsules or injection
• Therapeutic dose is generally 20-50 times higher than RDA
MCQ’S
Q. Daily requirement of Vitamin A for normal male adult
1.50 microgram
2. 550 microgram
3. 1000 microgram
4. 1500 microgram
Q. Deficiency of Vitamin A leads to
1.anaemia
2.nyctalopia
3.G6PD
4.Rickets
CASE STUDY
Jennie Davis, a 15-year-old with a history of cystic fibrosis, had been
experiencing progressive decreased vision and difficulty with her night
vision in both eyes for almost three years.
After seeing her primary care physician, she was referred to our clinic
for evaluation.
• Q. What is the probable diagnosis
• Q. Justify the diagnosis
Bibliography
• Lippincott Illustrated Reviews: Biochemistry
• Textbook of biochemistry for medical students by DM Vasudevan
• Www.wikipwdia.org
ACKNOWLEDGMENT
I would like to express my special thanks to my supervisors and
colleagues Mahiya Maheshwari , Aaradhya Solanki and Anushka
Chauhan who helped me in making the presentation.
Thanks to everyone who helped
THANK YOU
