Dr. P. N. ANSIL
What are vitamins ?
 Essential organic compounds that are required in small
amounts for normal growth, maintenance of good health
and for the proper utilization of other nutrients.
 Nutrients that our body does not make on its own. Thus
we must obtain them from the foods we eat, or via vitamin
supplements.
VITAMINS
Fat Soluble
Vitamin A
Vitamin D
Vitamin E
Vitamin K
Water Soluble
B-Complex
Energy
releasing
Thiamine
Riboflavin
Niacin
Pyridoxine
Biotin
Pantothenic
acid
Hematopoietic
Folic acid
Vitamin
B12
Non B-
Complex Vitamin C
Classification of
Vitamins
Fat soluble vitamins
• Soluble in fat
• Absorbed along with other lipids
• Requires carrier proteins
• Stored in liver
• Deficiency manifests only when
stores are depleted
• Toxicity - Hypervitaminosis may
result
• Single large does may prevent
deficiency
• E.g. A,D,E & K
• Soluble in water
• Absorption is simple
• No requirement of carrier protein
• Excreted in urine
• Deficiency manifests rapidly as
there is no storage
• Unlikely , since excess is excreted
• Regular dietary supply is required
• E.g. B complex & C
Difference between fat soluble and water soluble vitamins
Water soluble vitamins
 Hydrophobic
 Isoprene derivatives
 They cannot be synthesized by the body
 Supplied by the diet
 Absorption along with fat
 Transport: By lipoprotein & Specific binding protein
 Surplus amount stored – liver & adipose tissue
 Excess consumption leads to accumulation & toxic effects.
Lipid soluble vitamins - common features
VITAMIN A
Introduction
• Vitamin A is an essential nutrient needed in small amounts
for the normal functioning of the visual system, and
maintenance of cell function for growth, epithelial integrity,
red blood cell production, immunity and reproduction.
• Vitamin A deficiency (VAD) is a major nutritional concern in
poor societies, especially in lower income countries like
INDIA.
Where does it come from?
Animal Sources
 Eggs
 Meat
 Cheese
 Milk
 Liver
 Kidney
 Fish liver oils
Plant Sources
 Carrots
 Sweet Potatoes
 Apricots
 Broccoli
 Spinach
 Pumpkin
 Papaya
 Mango
Vitamin A
(Preformed and Provitamin)
• Retinoids: Natural & synthetic forms of Vitamin A
• Preformed: Three preformed compounds that are metabolically
active and found in animal products
– Retinol – alcohol form
– Present in animal tissues as retinyl ester with long chain
fatty acid
– Retinal or retinaldehyde – aldehyde form
– Obtained by oxidation of retinol
– Retinal & Retinol are interconvertible
– Retinoic acid – acid form
– Produced by oxidation of Retinal
• Provitamin: Carotenoids (β-carotene) can yield 2
retinols when metabolized in the body
• β -carotene
 found in plants
 Has 2 β-ionone rings connected by a polyprenoid
chain
Absorption
• Retinoids
– Retinyl esters broken down to free retinol & FA in small
intestine - requires bile, digestive enzymes, integration into
micelles
– Once absorbed, retinyl esters reformed in intestinal cells
– 90% of retinoids can be absorbed
• Carotenoids
– Absorbed intact, absorption rate much lower
– Intestinal cells can convert carotenoids to retinoids
• Approximately 80% is absorbed.
• It is passed along with fat through the lymphatic system
into blood stream.
• Absorption is poor in case of diarrhea, jaundice and
abdominal disorder.
• Absorption increases if taken with fat.
• Vitamin A which is not absorbed is excreted within 1 or 2
days in feces .
Transport
• Transported via chylomicrons from intestinal cells to the
liver
• Transported from the liver to target tissue as retinol via
retinol-binding protein (RBP; MW. 21,000).
From intestine to Liver
From liver to tissue
Plasma retinol binding protein(RBP)– to cell membrane-
Cellular retinoic-acid binding protein(CRBP) –retinol—
cytoplasm—HRE—GENE EXPRESSION
Chylomicron
Summary of Vitamin A
absorption
Summary of the functions of Vitamin A
compounds
Storage
• The liver has enormous capacity to store in the form of
retinol palmitate.
• Under normal conditions a well-fed person has sufficient
Vitamin A reserves to meet his need for 6 to 9months or
more.
Excretion of Vitamin A
• Not readily excreted
• Kidney disease and aging increase risk of toxicity because
excretion is impaired
Functions of Vitamin A
 Vision: Vitamin A is a component of the visual pigment
rhodopsin. Retinal is bound to the protein opsin.
 Growth: Vitamin A deficiency causes loss of appetite. Slow
bone growth. Affects CNS.
 Reproduction: Retinol and retinal are essential for normal
reproduction
 Maintenance of epithelial cells: Essential for normal
differentiation of epithelial tissues and mucus secretion
Role of Vitamin A in Vision
Visual Cycle (Wald’s Visual Cycle)
 A process by which light impacting on the retina of the eye
is converted to an electrical signal
 The optic nerve carries the electrical signal to the brain
(nerve impulse)
 The brain processes the signal into an image
Role of Vitamin A in Vision
 Retina is a light-sensitive layer of cells at the back of the
eye where an image is formed
 Retina consists of: Rod and cone cells (photosensitive
cells)
 Rod cells process & image
 Cone cells process color image
Rod Cell
Cone Cell
Role of Vitamin A in Vision
 Normal vision depends on the retina and on adequate
vitamin A
 In the retina, vitamin A in the form of retinal binds to a
protein called opsin to make rhodopsin [11-cis – retinal-
opsin] in rod cells
 Rhodopsin is a light-sensitive pigments
Wald’s Visual Cycle
The Visual
Cycle
Role of Vitamin A in Vision
 When stimulated by light, vitamin A isomerizes from its
bent ‘cis’ form to a straighter ‘trans’ form and detaches
from opsin
 The opsin molecule changes shape, which sends a signal to
the brain via optic nerve and an image is formed
 Most retinal released in this process is quickly converted to
trans-retinol and then to cis-retinal, to begin another cycle
Role of Vitamin A in Vision
Dark Adaptation time
 Bright light depletes rhodopsin (photobleaching)
 Sudden shift from bright light to darkness causes
difficulty in seeing
 Rhodopsin is synthesized in a few minutes and vision is
improved in the dark
Role of Vitamin A in Vision
 The time required to synthesize rhodopsin in the dark is
called dark adaptation time
 It is increased in vitamin A deficiency
Bleaching of Rhodopsin
• Bleaching - When exposed to light, the colour of
rhodopsin changes from red to yellow
• Occurs in a few milliseconds
• Unstable intermediates are formed
Rhodopsin Prelumirhodopsin Lumirhodopsin
Metarhodopsin IMetarhodopsin IIAll-trans-retinal +
Opsin
• Light strikes the retina – biochemical changes –
membrane hyperpolarization – generate nerve impulse.
• Hyperpolarization of the membrane is brought about by
a visual cascade involving cGMP
Visual cascade and cGMP
Visual cascade involving cGMP
• Decrease in cGMP closes
the Na+ channels in the
membranes of the rod
cells
• Result in
hyperpolariztion – an
excitatory response
transmitted through the
neuron network to the
visual cortex of the
brain
Colour vision
• Cones are specialized in bright and colour vision
• Governed by colour sensitive pigmens
iodopsin – green
cyanopsin – blue
porphyropsin – red
• These pigments are complexes of protein & Vitamin A
• Bright light strikes retina – depending on the
particular colour of the light – one or more pigments
are bleached – passes nerve impulse to brain as
specific colour
Functions of Vitamin A:
Growth and Differentiation of Cells
• Retinoic acid is necessary for cellular differentiation
• Important for embryo development, gene expression
• Retinoic acid influences production, structure, and
function of epithelial cells that line the outside (skin)
and external passages (mucus forming cells) within the
body
Epithelial cell ‘integrity’
• Many epithelial cell require Vitamin A for proper
differentiation and maintenance
• Lack of Vitamin A leads to dysfunction of epithelia
– The skin becomes keratinized and scaly, and mucus
secretion is suppressed
Functions of Vitamin A: Immunity
• Deficiency leads to decreased resistance to infections
• Supplementation may decrease severity of infections in
deficient person
• Role in Prevention of cardiovascular disease
– Antioxidant capabilities
• Role in Cancer prevention
– Antioxidant capabilities
– Lung, oral, and prostate cancers
– Studies indicate that vitamin A-containing foods are more
protective than supplements
What does RDA mean?
• Recommended Dietary Allowances
• These are suggested levels of essential nutrients
considered adequate to meet nutritional needs of healthy
individuals.
Infants and children - 400-600µg/day
Men -750-1000µg/day
Women -750µg/day
Pregnancy -1000µg/day
Lactation -1200µg/day
Vitamin A Deficiency and Diseases
 Nyctalopia (night blindness)
 Xerophthalmia
 Bitot’s spots
 Keratomalacia
 Complete blindness (in severe deficiency)
1. Night Blindness
• Visual acuity is diminished in dim
light
• Occurs as a result of inadequate
pigment in the retina.
• The dark adaptation time is
increased
• Found in pregnant women in
some instances, especially during
the last trimester of pregnancy
when the vitamin A needs are
increased.
 It is the most specific VAD,
and is the leading
preventable cause of
blindness
 Conjunctiva becomes dry,
thick and wrinkled
 Conjunctiva gets keratinized
and loses its normal
transparency
 Cornea becomes glazy &
lusterless
2. Xerophthalmia
3. Bitot’s Spot
• Tissue spots that develop around
the eye ball, causing severe
dryness in the eyes.
• Seen as grayish-white triangular
plaques firmly adherent to the
conjunctiva.
4.Keratomalacia
• One of the major cause for
blindness in India.
• Cornea becomes soft and may
burst
• Prolonged xerophthalmia
leads to keratomalacia
(softening of the cornea)
• If the eye collapses vision is
lost.
Other Symptoms of VAD
• Alteration of skin and mucous membrane
• Hepatic dysfunction
• Headache
• Drowsiness
• Peeling of skin
• Dark adaptation test
• Serum RBP
• Serum vitamin A
25 – 50 µg/dl
ASSESSMENT OF DEFICIENCY
1) Eating of polar bear liver
2) Excess supplementation of
Vitamin A
When?
TOXICITY
One ounce of polar bear
liver contains enough
vitamin A (retinol) to kill a
person!
• Hepatomegaly
• Increased cerebrospinal fluid pressure
• Disturbance in calcium homeostasis – skletal
decalcificaion – tendrness of long bones
• Skin - Excessive dryness, desquamation
TOXICITY
1.Dietary Deficiency
2. Retinoic acid
a. Psoriasis
b. Pro-myelocytic leukemia
c. Acne
THERAPEUTIC USES
Thank you

Vitamin A

  • 1.
    Dr. P. N.ANSIL
  • 2.
    What are vitamins?  Essential organic compounds that are required in small amounts for normal growth, maintenance of good health and for the proper utilization of other nutrients.  Nutrients that our body does not make on its own. Thus we must obtain them from the foods we eat, or via vitamin supplements.
  • 3.
    VITAMINS Fat Soluble Vitamin A VitaminD Vitamin E Vitamin K Water Soluble B-Complex Energy releasing Thiamine Riboflavin Niacin Pyridoxine Biotin Pantothenic acid Hematopoietic Folic acid Vitamin B12 Non B- Complex Vitamin C Classification of Vitamins
  • 4.
    Fat soluble vitamins •Soluble in fat • Absorbed along with other lipids • Requires carrier proteins • Stored in liver • Deficiency manifests only when stores are depleted • Toxicity - Hypervitaminosis may result • Single large does may prevent deficiency • E.g. A,D,E & K • Soluble in water • Absorption is simple • No requirement of carrier protein • Excreted in urine • Deficiency manifests rapidly as there is no storage • Unlikely , since excess is excreted • Regular dietary supply is required • E.g. B complex & C Difference between fat soluble and water soluble vitamins Water soluble vitamins
  • 5.
     Hydrophobic  Isoprenederivatives  They cannot be synthesized by the body  Supplied by the diet  Absorption along with fat  Transport: By lipoprotein & Specific binding protein  Surplus amount stored – liver & adipose tissue  Excess consumption leads to accumulation & toxic effects. Lipid soluble vitamins - common features
  • 6.
  • 7.
    Introduction • Vitamin Ais an essential nutrient needed in small amounts for the normal functioning of the visual system, and maintenance of cell function for growth, epithelial integrity, red blood cell production, immunity and reproduction. • Vitamin A deficiency (VAD) is a major nutritional concern in poor societies, especially in lower income countries like INDIA.
  • 8.
    Where does itcome from? Animal Sources  Eggs  Meat  Cheese  Milk  Liver  Kidney  Fish liver oils Plant Sources  Carrots  Sweet Potatoes  Apricots  Broccoli  Spinach  Pumpkin  Papaya  Mango
  • 9.
    Vitamin A (Preformed andProvitamin) • Retinoids: Natural & synthetic forms of Vitamin A • Preformed: Three preformed compounds that are metabolically active and found in animal products – Retinol – alcohol form – Present in animal tissues as retinyl ester with long chain fatty acid – Retinal or retinaldehyde – aldehyde form – Obtained by oxidation of retinol – Retinal & Retinol are interconvertible – Retinoic acid – acid form – Produced by oxidation of Retinal
  • 10.
    • Provitamin: Carotenoids(β-carotene) can yield 2 retinols when metabolized in the body • β -carotene  found in plants  Has 2 β-ionone rings connected by a polyprenoid chain
  • 13.
    Absorption • Retinoids – Retinylesters broken down to free retinol & FA in small intestine - requires bile, digestive enzymes, integration into micelles – Once absorbed, retinyl esters reformed in intestinal cells – 90% of retinoids can be absorbed • Carotenoids – Absorbed intact, absorption rate much lower – Intestinal cells can convert carotenoids to retinoids
  • 14.
    • Approximately 80%is absorbed. • It is passed along with fat through the lymphatic system into blood stream. • Absorption is poor in case of diarrhea, jaundice and abdominal disorder. • Absorption increases if taken with fat. • Vitamin A which is not absorbed is excreted within 1 or 2 days in feces .
  • 15.
    Transport • Transported viachylomicrons from intestinal cells to the liver • Transported from the liver to target tissue as retinol via retinol-binding protein (RBP; MW. 21,000). From intestine to Liver From liver to tissue Plasma retinol binding protein(RBP)– to cell membrane- Cellular retinoic-acid binding protein(CRBP) –retinol— cytoplasm—HRE—GENE EXPRESSION Chylomicron
  • 17.
    Summary of VitaminA absorption
  • 18.
    Summary of thefunctions of Vitamin A compounds
  • 19.
    Storage • The liverhas enormous capacity to store in the form of retinol palmitate. • Under normal conditions a well-fed person has sufficient Vitamin A reserves to meet his need for 6 to 9months or more.
  • 20.
    Excretion of VitaminA • Not readily excreted • Kidney disease and aging increase risk of toxicity because excretion is impaired
  • 21.
    Functions of VitaminA  Vision: Vitamin A is a component of the visual pigment rhodopsin. Retinal is bound to the protein opsin.  Growth: Vitamin A deficiency causes loss of appetite. Slow bone growth. Affects CNS.  Reproduction: Retinol and retinal are essential for normal reproduction  Maintenance of epithelial cells: Essential for normal differentiation of epithelial tissues and mucus secretion
  • 22.
    Role of VitaminA in Vision Visual Cycle (Wald’s Visual Cycle)  A process by which light impacting on the retina of the eye is converted to an electrical signal  The optic nerve carries the electrical signal to the brain (nerve impulse)  The brain processes the signal into an image
  • 23.
    Role of VitaminA in Vision  Retina is a light-sensitive layer of cells at the back of the eye where an image is formed  Retina consists of: Rod and cone cells (photosensitive cells)  Rod cells process & image  Cone cells process color image
  • 25.
  • 26.
    Role of VitaminA in Vision  Normal vision depends on the retina and on adequate vitamin A  In the retina, vitamin A in the form of retinal binds to a protein called opsin to make rhodopsin [11-cis – retinal- opsin] in rod cells  Rhodopsin is a light-sensitive pigments
  • 27.
  • 28.
  • 29.
    Role of VitaminA in Vision  When stimulated by light, vitamin A isomerizes from its bent ‘cis’ form to a straighter ‘trans’ form and detaches from opsin  The opsin molecule changes shape, which sends a signal to the brain via optic nerve and an image is formed  Most retinal released in this process is quickly converted to trans-retinol and then to cis-retinal, to begin another cycle
  • 30.
    Role of VitaminA in Vision Dark Adaptation time  Bright light depletes rhodopsin (photobleaching)  Sudden shift from bright light to darkness causes difficulty in seeing  Rhodopsin is synthesized in a few minutes and vision is improved in the dark
  • 31.
    Role of VitaminA in Vision  The time required to synthesize rhodopsin in the dark is called dark adaptation time  It is increased in vitamin A deficiency
  • 32.
    Bleaching of Rhodopsin •Bleaching - When exposed to light, the colour of rhodopsin changes from red to yellow • Occurs in a few milliseconds • Unstable intermediates are formed Rhodopsin Prelumirhodopsin Lumirhodopsin Metarhodopsin IMetarhodopsin IIAll-trans-retinal + Opsin
  • 33.
    • Light strikesthe retina – biochemical changes – membrane hyperpolarization – generate nerve impulse. • Hyperpolarization of the membrane is brought about by a visual cascade involving cGMP Visual cascade and cGMP
  • 34.
    Visual cascade involvingcGMP • Decrease in cGMP closes the Na+ channels in the membranes of the rod cells • Result in hyperpolariztion – an excitatory response transmitted through the neuron network to the visual cortex of the brain
  • 35.
    Colour vision • Conesare specialized in bright and colour vision • Governed by colour sensitive pigmens iodopsin – green cyanopsin – blue porphyropsin – red • These pigments are complexes of protein & Vitamin A • Bright light strikes retina – depending on the particular colour of the light – one or more pigments are bleached – passes nerve impulse to brain as specific colour
  • 36.
    Functions of VitaminA: Growth and Differentiation of Cells • Retinoic acid is necessary for cellular differentiation • Important for embryo development, gene expression • Retinoic acid influences production, structure, and function of epithelial cells that line the outside (skin) and external passages (mucus forming cells) within the body
  • 37.
    Epithelial cell ‘integrity’ •Many epithelial cell require Vitamin A for proper differentiation and maintenance • Lack of Vitamin A leads to dysfunction of epithelia – The skin becomes keratinized and scaly, and mucus secretion is suppressed
  • 39.
    Functions of VitaminA: Immunity • Deficiency leads to decreased resistance to infections • Supplementation may decrease severity of infections in deficient person
  • 40.
    • Role inPrevention of cardiovascular disease – Antioxidant capabilities • Role in Cancer prevention – Antioxidant capabilities – Lung, oral, and prostate cancers – Studies indicate that vitamin A-containing foods are more protective than supplements
  • 41.
    What does RDAmean? • Recommended Dietary Allowances • These are suggested levels of essential nutrients considered adequate to meet nutritional needs of healthy individuals. Infants and children - 400-600µg/day Men -750-1000µg/day Women -750µg/day Pregnancy -1000µg/day Lactation -1200µg/day
  • 42.
    Vitamin A Deficiencyand Diseases  Nyctalopia (night blindness)  Xerophthalmia  Bitot’s spots  Keratomalacia  Complete blindness (in severe deficiency)
  • 43.
    1. Night Blindness •Visual acuity is diminished in dim light • Occurs as a result of inadequate pigment in the retina. • The dark adaptation time is increased • Found in pregnant women in some instances, especially during the last trimester of pregnancy when the vitamin A needs are increased.
  • 44.
     It isthe most specific VAD, and is the leading preventable cause of blindness  Conjunctiva becomes dry, thick and wrinkled  Conjunctiva gets keratinized and loses its normal transparency  Cornea becomes glazy & lusterless 2. Xerophthalmia
  • 45.
    3. Bitot’s Spot •Tissue spots that develop around the eye ball, causing severe dryness in the eyes. • Seen as grayish-white triangular plaques firmly adherent to the conjunctiva.
  • 46.
    4.Keratomalacia • One ofthe major cause for blindness in India. • Cornea becomes soft and may burst • Prolonged xerophthalmia leads to keratomalacia (softening of the cornea) • If the eye collapses vision is lost.
  • 47.
    Other Symptoms ofVAD • Alteration of skin and mucous membrane • Hepatic dysfunction • Headache • Drowsiness • Peeling of skin
  • 48.
    • Dark adaptationtest • Serum RBP • Serum vitamin A 25 – 50 µg/dl ASSESSMENT OF DEFICIENCY
  • 49.
    1) Eating ofpolar bear liver 2) Excess supplementation of Vitamin A When? TOXICITY One ounce of polar bear liver contains enough vitamin A (retinol) to kill a person!
  • 50.
    • Hepatomegaly • Increasedcerebrospinal fluid pressure • Disturbance in calcium homeostasis – skletal decalcificaion – tendrness of long bones • Skin - Excessive dryness, desquamation TOXICITY
  • 51.
    1.Dietary Deficiency 2. Retinoicacid a. Psoriasis b. Pro-myelocytic leukemia c. Acne THERAPEUTIC USES
  • 52.