Vitamin A is a lipid-soluble vitamin essential for various bodily functions, particularly vision, immune support, and cell growth. It has multiple forms, including retinol, retinal, and retinoic acid, and is primarily sourced from animal products and certain vegetables rich in beta-carotene. Deficiency can lead to serious visual impairments such as night blindness and xerophthalmia, while excess intake can cause toxicity with severe health effects.

1. vitamin A
METABOLISM AND FUNCTION

2. Introduction
• Vitamins are essential micronutrients required by the body in small amounts to
support a range of vital functions. Vitamins are divided into two groups: water-
soluble vitamins (B-complex vitamin and vitamin C), lipid- soluble vitamins
(vitamin A, K, E, and D). Lipid- soluble vitamins are stored in the liver and fatty
tissue for long periods of time, and generally pose a greater risk for toxicity than
water-soluble vitamins when consumed in excess.

3. Structure of vitamin A
• The retinoids include the natural form of vitamin A, retinol and its metabolites and synthetic form like drugs.
1. Retinol: It’s the storage form of vitamin A, primary alcohol containing a β-ionone ring with an unsaturated
side chain, retinol is found in animal tissues as a retinyl ester with long-chain fatty acid.
2. Retinal: This is the aldehyde derived from the oxidation of retinol. Retinal and retinol can readily be
interconverted.
3. Retinoic acid: This is the acid derived from the oxidation of retinal. Retinoic acid cannot be reduced in the
body and, therefore, cannot give rise to either retinal or retinol.
4. β-Carotene: Plant foods contain β-carotene (provitamin A), which can be oxidatively and symmetrically
cleaved in the intestine to yield two molecules of retinal. In humans, the conversion is inefficient, and the
vitamin A activity of β-carotene is only about 1/12 that of retinol.

4. Metabolism

5. • Retinyl esters from the diet are hydrolyzed in the intestinal mucosa, releasing retinol and free fatty acid.
Retinol derived from esters and from the reduction of retinal from β-carotene cleavage is re-esterified to
long-chain fatty acid within the enterocytes and secreted as a component of chylomicrons into the lymphatic
system. Retinyl esters contained in chylomicron remnants are taken up by, and stored in, the liver.
Absorption and transport to the liver:

6. Release from the liver:
• Retinyl esters from the diet are hydrolyzed in the intestinal mucosa, releasing retinol and free
fatty acid. Retinol derived from esters and from the reduction of retinal from β-carotene cleavage
is re-esterified to long-chain fatty acid within the enterocytes and secreted as a component of
chylomicrons into the lymphatic system. Retinyl esters contained in chylomicron remnants are
taken up by, and stored in, the liver.

7. Retinoic acid mechanism of action:
• Retinol is oxidized to retinoic acid. Retinoic acid binds with high affinity to specific receptor proteins (retinoic
acid receptors [RAR]) present in the nucleus of target tissues such as epithelial cells. The activated retinoic
acid–RAR complex binds to response elements on DNA and recruit’s activators or repressors to regulate
retinoid-specific RNA synthesis, resulting in control of the production of specific proteins that mediate
several physiologic functions. For example, retinoids control the expression of the gene for keratin in most
epithelial tissues of the body.

9. • Eating a wide variety of foods is the best way to ensure that the body gets enough vitamin A. The retinol,
retinal, and retinoic acid forms of vitamin A are supplied primarily by foods of animal origin such as dairy
products, fish and liver. Some foods of plant origin contain the antioxidant, β-Carotene, which the body
converts to vitamin A. β-Carotene, comes from fruits and vegetables, especially those that are orange or dark
green in colour. Vitamin A sources also include carrots, pumpkin, winter squash, dark green leafy
vegetables and apricots, all of which are rich in beta-carotene.

10. function of vitamin
A

11. • Vitamin A plays a key role in developing and supporting our vision, keeping
our immune system functioning properly and helping our cells and tissues
grow and develop. Vitamin A is particularly important for reproduction, as
it helps the normal growth and development of the embryo. Epithelial cell
maintenance: Vitamin A is essential for normal differentiation of epithelial
tissues and mucus secretion and, thus, supports the body’s barrier-based
defence against pathogens.
• Reproduction: Retinol and retinal are essential for normal reproduction,
supporting spermatogenesis in the male and preventing fetal resorption in
the female. Retinoic acid is inactive in maintaining reproduction and in the
visual cycle but promotes growth and differentiation of epithelial cell.

12. Regulation of gene expression and
tissue differentiation:
• A major role of vitamin A is the control of cell differentiation and turnover. All-trans-retinoic acid and 9-cis-
retinoic acid regulate growth, development, and tissue differentiation they have different actions in different
tissues. retinoic acid binds to nuclear receptors that bind to response elements of DNA and regulate the
transcription of specific genes. there are two families of nuclear retinoid receptors: the retinoic acid
receptors (RAR) bind all-trans-retinoic acid or 9-cis-retinoic acid, and the retinoid X receptors (RXR) bind 9-
cis-retinoic acid. RXRs also form hetero dimers with vitamin D, thyroid, and other nuclear acting hormone
receptors. Deficiency of vitamin A impairs vitamin D and thyroid hormone function because of lack of 9-cis-
retinoic acid to form active receptor dimers. Unoccupied RXRs form dimers with occupied vitamin D and
thyroid hormone receptors, but not only are these unable to activate gene expression, they may repress it.
Consequently, vitamin A deficiency has a more severe effect on vitamin D and thyroid hormone function
than simply interfering with gene expression. Excessive vitamin A also impairs vitamin D and thyroid
hormone function, because of formation of RXR homodimers, meaning that there are not enough diseases.
the synthesis of retinol-binding protein, which is required to transport the vitamin in the bloodstream, is
reduced in response to infection (it is a negative acute phase protein), decreasing the circulating
concentration of the vitamin, and further impairing immune responses.

14. Vision (vision cycle):
• In the retina, retinaldehyde functions as the prosthetic group of the light-sensitive opsin proteins, forming
rhodopsin (in rods) and iodopsin (in cones). Any one cone cell contains only one type of opsin and is
sensitive to only one colour. In the pigment epithelium of the retina, all-trans-retinol is isomerized to 11-cis-
retinol and oxidize to 11-cis-retinaldehyde. this reacts with a lysine residue in opsin, forming the holoprotein
rhodopsin, the absorption of light by rhodopsin causes isomerization of the retinaldehyde from 11-cis to all-
trans, and a conformational change in opsin. this results in the release of retinaldehyde from the protein,
and the initiation of a nerve impulse. the formation of the initial excited form of rhodopsin, bathorhodopsin,
occurs within picoseconds of illumination. there is then a series of conformational changes leading to the
formation of metarhodopsin II, which initiates a guanine nucleotide amplification cascade and then a nerve
impulse. the final step is hydrolysis to release all-trans-retinaldehyde and opsin. the key to initiation of the
visual cycle is the availability of 11-cis-retinaldehyde, and hence vitamin A. In deficiency, both the time taken
to adapt to darkness and the ability to see in poor light are impaired.

15. Dark adaptation:
• The eye operates over a large range of light levels. The sensitivity of our eye can be measured by
determining the absolute intensity threshold, that is, the minimum luminance of a test spot required to
produce a visual sensation. This can be measured by placing a subject in a dark room and increasing the
luminance of the test spot until the subject reports its presence. Consequently, dark adaptation refers to
how the eye recovers its sensitivity in the dark after exposure to bright lights.
• Bright light depletes rhodopsin, sudden shift from bright light to darkness cause difficulty in seeing,
rhodopsin is synthetized in a few minutes and vision is improved in the dark, the time required to synthesize
rhodopsin in the dark is called dark adaptation time. Dark adaptation time increase in vitamin A deficiency.

17. Deficiency:
• Vitamin A, administered as retinol or retinyl esters, is used to treat patients
who are deficient in the vitamin. Night blindness (nyctalopia) is one of the
earliest signs of vitamin A deficiency. The visual threshold is increased,
making it difficult to see in dim light. Prolonged deficiency leads to an
irreversible loss in the number of visual cells. Severe deficiency leads to
xerophthalmia, a pathologic dryness of the conjunctiva and cornea, caused,
in part, by increased keratin synthesis. If untreated, xerophthalmia results
in corneal ulceration and, ultimately, in blindness because of the formation
of opaque scar tissue. The condition is most seen in children in developing
tropical countries. Over 500,000 children worldwide are blinded each year
by xerophthalmia caused by insufficient vitamin A in the diet.

18. Nyctalopia:
• 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 principal cell-type associated with Nyctalopia is rod cells. Rods are a type of photoreceptor cell
present in the retina that transmits low-light vision and is most responsible for the neural transmission of
nighttime sight. Rods have a singular photopigment, rhodopsin, which utilizes the protein scotopsin and the
Vitamin A-derived cofactor. This cascade is essential for the body's ability to regulate the pupillary light
reflex. The pupillary light reflex allows unilateral afferent detection of changes in light energy entering the
eye, and efferent adjustments in the pupillary sphincter and dilator pupillae muscles to initiate consensual
constriction and dilation of the eyes. Pupil dilation is an adaptive response to changes in lightness and
darkness. Night blindness is the physical manifestation of impaired functioning of these processes.
Xerophthalmia:
• Xerophthalmia is a progressive eye disease caused by vitamin A deficiency. Lack of vitamin A can
dry out tear ducts and eyes. Xerophthalmia can develop into night blindness or more serious
damage in the cornea. This damage may take the form of white spots on eyes and ulcers on the
corneas.

19. Bitot’s spots:
• are triangular deposits that can form on the whites of the
eyes. They are made up of dried conjunctiva, the clear layer
on the outside of the eye.
Keratomalacia:
• Keratomalacia is an eye condition in which the cornea, the clear front part of the eye, gets cloudy and
softens. This eye disease often starts as xerophthalmia, which is severe dryness of the cornea and
conjunctiva. If Keratomalacia is not treated, the softening of your corneas can lead to infection, rupture, and
tissue changes that may result in blindness. Keratomalacia is also known as xerotic keratitis and corneal
melting.

20. Blindness:
• In its most severs forms, vitamin A deficiency contributes to blindness by making the cornea very dry, thus
damaging the retina and cornea.

21. RDA (The Recommended Dietary Allowance):
• The recommended dietary for adults is 900 retinol activity equivalents (RAE) for males and 700 RAE for
females. In comparison, 1 RAE = 1 µg of retinol, 12 µg of β-carotene, or 24 µg of other carotenoids.

22. Clinical indication for vitamin A:
• Although chemically related, retinoic acid and retinol have
distinctly different therapeutic applications. Retinol and its
carotenoid precursor are used as dietary supplements, whereas
various forms of retinoic acid are useful in dermatology.

23. Vitamin A is toxic in excess:
• Humans possess only a limited capacity to metabolize vitamin A, and
excessive intakes lead to accumulation beyond the capacity of
intracellular binding proteins, unbound vitamin A causes membrane
lysis and tissue damage. Symptoms of toxicity affect the central
nervous system (headache, nausea, ataxia, and anorexia, all
associated with increased cerebrospinal fluid pressure); the liver
(hepatomegaly with histological changes and hyperlipaemia); calcium
homeostasis (thickening of the long bones, hypercalcemia, and
calcification of soft tissues); and the skin (excessive dryness,
desquamation, and alopecia).