Vitamin A
• Deficiency of vitamin A is the most common cause
of non-accidental blindness, worldwide
• Preformed
– Retinoids (retinal, retinol, retinoic acid)
– Found in animal products
• Provitamin A
– Carotenoids
– Must be converted to retinoid form
– Intestinal cells can split carotene in two (molecules of retinoids)
– Found in plant products
Lipid-soluble vitamins
Vitamin A
Retinol
• Biologically active forms - Cyklohexan ring and isoprenoid
retinoids: retinol, retinal, chain
retinoid acid.
• Major vit. A precursors
(provitamins) → plants
carotenoids.
• Foodstaf of animals origin
contain most of vit. A in the
form of esters (retinylpalmi-
tates) – retinol and long fatty
acid
Terminal Ends of Retinoids
Conversion of Carotenoids to
Retinoids
• Enzymatic conversion of
carotenoids occurs in liver or
intestinal cells, forming retinal and
retinoic acid
• Provitamin A carotenoids
– Beta-carotene
– Alpha carotene
– Beta-cryptoxanthin
• Other carotenoids
– Lutein
– Lycopene
– Zeaxanthin
Absorption of Vitamin A
• Retinoids
– Retinyl esters broken down to free retinol 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
Transport and Storage of Vitamin A
• Liver stores 90% of vitamin A in the body
• Reserve is adequate for several months
• Transported via chylomicrons from intestinal
cells to the liver
• Transported from the liver to target tissue as
retinol via retinol-binding protein.
Retinoid Binding Proteins
• Target cells contain
cellular retinoid binding
proteins
– Direct retinoids to
functional sites within cells
– Protect retinoids from
degradation
• RAR, RXR receptors on
the nucleus
– Retinoid-receptor complex
binds to DNA
– Directs gene expression
Excretion of Vitamin A
• Not readily excreted
• Some lost in urine
• Kidney disease and aging increase risk of
toxicity because excretion is impaired
Functions of Vitamin A: Vision
• Retinal turns visual light into nerve signals in
retina of eye
• Retinoic acid required for structural
components of eye
– Cones in the retina
• Responsible for vision under bright lights
• Translate objects to color vision
– Rods in the retina
• Responsible for vision in dim lights
• Translate objects to black and white vision
Vitamin A and vision
• Vit. A is necessary to form rhodopsin (in
rodes, night vision) and iodopsins
(photopsins, in cones – color vision) -
visual pigment.
• Retinaldehyd is a prosthetic group of
light-sensitive opsin protein.
• In the retina, all-trans-retinol is
isomerized to 11-cis-retinol → oxidized
to 11-cis-retinaldehyd, this reacts with
opsin (Lys) → to form the holoprotein
rhodopsin.
• Absorption of light → conformation
changes of opsin → photorhodopsin.
The Visual Cycle
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
Vitamin A and other functions
Transcription and cell differentiation
• Retinoic acid regulates the transcription of genes - acts through nuclear
receptors (steroid-like receptors).
Retinol retinal retinoic acid
Retinol dehydrogease Retinaldehyde dehydrogenasa
• By binding to various nuclear receptors, vit. A stimulates (RAR – retinoid acid
receptor) or inhibits (RXR- retinoid „X“ receptor) transcription of genes
transcription. All-trans-retinoic acid binds to RAR and 9-cis-retinoic acid
binds to RXR.
• Retinoic acid is necessary for the function and maintenance of epithelial
tissues.
AF1 LBD - AF2
DBD Helix 12
A/B C D E/F
Nuclear Hormone Receptor
Superfamily
Type I family Type II family
Steroid family Non-steroid family
GR TR ,
PR RAR ,
AR VDR RXR ,
MR PPAR ,
ER , CAR, SXR/PXR
LXR ,, FXR
Diverse Structure of Ligands for Nuclear Receptors
Nuclear Receptors
Transcription Factors regulated by
hydrophobic molecules
Functions of Vitamin A:
Immunity
• Deficiency leads to decreased resistance
to infections
• Supplementation may decrease severity of
infections in deficient person
Vitamin A Analogs for Acne
• Topical treatment (Retin-A)
– Causes irritation, followed by peeling of skin
– Antibacterial effects
• Oral treatment
– Regulates development of skin cells
– Caution regarding birth defects
Possible Carotenoid Functions
• Prevention of cardiovascular disease
– Antioxidant capabilities
– ≥5 servings/day of fruits and vegetables
• Cancer prevention
– Antioxidant capabilities
– Lung, oral, and prostate cancers
– Studies indicate that vitamin A-containing foods are
more protective than supplements
• Age-related macular degeneration
• Cataracts
• In general, foods rich in vitamin A and other
phytochemicals are advised rather than
supplements
Vitamin A in Foods
• Preformed
– Liver, fish oils, fortified milk,
eggs, other fortified foods
– Contributes ~70% of vitamin A intake for
Americans
• Provitamin A carotenoids
– Dark leafy green, yellow-orange
vegetables/fruits
Deficiency of Vitamin A
• Consequences:
• Most susceptible
– Night blindness
populations: – Decreased mucus
– Preschool children production
with low F&V intake – Decreased immunity
– Bacterial invasion of the
– Urban poor
eye
– Older adults – Conjunctival xerosis
– Alcoholism – Bitot’s spots
– Liver disease (limits – Xerophthalmia
– Irreversible blindness
storage)
– Follicular hyperkeratosis
– Fat malabsorption – Poor growth
Upper Level for Vitamin A
• 3000 μg retinol
• Hypervitaminosis A results from long-
term supplement use (2 – 4 x RDA)
• Toxicity
• Fatal dose (12 g)
Toxicity of Vitamin A
– Acute – short-term megadose (100 x
RDA); symptoms disappear when intake
stops
• Headaches
• Blurred vision
• Poor muscle coordination
Toxicity of Vitamin A
– Chronic – long-term megadose; possible
permanent damage
• Bone and muscle pain
• Loss of appetite
• Skin disorders
• Headache
• Dry skin
• Hair loss
• Increased liver size
• Vomiting
Toxicity of Vitamin A
• Teratogenic (may occur with as little as 3 x
RDA of preformed vitamin A)
– Tends to produce physical defect on
developing fetus as a result of excess vitamin
A intake
– Spontaneous abortion
– Birth defects
Health Effects of Vitamin A
Toxicity of Carotenoids
• Not likely, as rate of conversion of carotenoids to
retinoic acid by liver is slow and efficiency of
absorption of carotenoids decreases as intake
increases
• Hypercarotenemia
– High amounts of carotenoids in the bloodstream
– Excessive consumption of carrots/squash/beta-carotene
supplements
– Skin turns a yellow-orange color
