Vitamin A

INTRODUCTION

In general, the term vitamin A is now used when reference is made to the biological activity of more than one vitamin A active substance. Three important forms of vitamin are shown in the box:

 

All three compounds contain as common structural unit:

1. A trimethyl cyclohexenyl ring (â-ionone) and

2. An all trans configurated polyene chain, (isoprenoid chain) with four double bonds.

3. They are crystalline substances with limited stability.

As already shown above, these three forms are

  i.             vitamin A alcohol or retinol,

ii.            vitamin A aldehyde or retinal (also called retinene) and

iii.            vitamin A acid or retinoic acid. These forms are sometimes referred to as retinoids. Vitamin A is a derivative of certain carotenoids which are hydrocarbon (polyene) pigments (yellow, red). These are widely distributed in the nature. These are called as “Provitamins A”and are  α ,βand γ -carotenes. Carotenes are C₄₀H₅₆ hydrocarbons.

Forms of vitamin A:

Differences between vitamin A1 and A2 are shown in a tabular form

Differences of vitamin A1 and vitamin A2
Vitamin A1		Vitamin A2
1. Found predominantly in major species of animal. 2. Shows absorption maximum at 693 mμ when treated 3. Only one double bond present in β-ionone ring. 4. More potent in its activity than vitamin A2 5. Can be obtained from carotenes	1. Found in fresh water fish liver and other tissues. 2. Shows absorption maximum at 620 mμ on treatment with SbCCl3. with SbCCl3 3. Two double bonds in β-ionone ring (additional double bond between (C3-C4) 4. Less potent, biological activity is approximately 40% that of A1. .5. Carotenes cannot give rise to vitamin A2.

CHEMICAL NAME OF VITAMIN A

(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohexen-1-yl)nona-2,4,6,8-tetraen-1-ol

STRUCTURES OF VITAMIN A

DIETARY SOURCES

• Animal sources: Liver oil, butter, milk, cheese, eggyolk.

• Plant sources: In the form of provitamin carotene, tomatoes, carrots, green-yellow vegetables, spinach, and fruits such as mangoes, papayas, corn, sweet potatoes. Spirulina species (algae) have been found to be a good source of vitamin A.

RECOMMENDED INTAKE OF VITAMIN A

 PHYSIOLOGICAL ROLE OF VITAMIN  A

1. Role in Vision

Perhaps the only function of vitamin A which is clearly understood to its molecular details is its role in vision. The overall machanism through which vitamin A functions in visual system is known as Wald’s visual cycle or “Rhodopsin cycle” discovered by George Wald for which he was awarded Nobel Prize . Retina contains two types of receptor cells:

(i) Cones: Specialised for colour and detail vision in

bright light contains iodopsin.

(ii) Rods: Specialised for visual activity in dim light (night

vision), contains rhodopsin.

2. Role in Reproduction

Experimental work with rats shows that vitamin A deficient male rats do not develop their testes properly in that they are oedematous and sperm cells do not develop to state of maturity. When such male rats are allowed to mate with normal fertile females, no conception takes place. In contrast, vitamin A deficient female rats maintain normal oestrous cycle and do conceive, but are unable to carry the pregnancy to full-term.

3. Role in Epithelialisation

The epithelial structures of skin and mucous membrane show gross structural changes in deficiency.

• Skin: Skin becomes dry, scaly and rough. These changes are called as keratinisation.

• Lacrimal glands: Similar changes occur in these glands leading to dryness of conjunctivae and cornea, a condition described as xerophthalmia.

• Cornea: White opaque spots called Bitot’s spots appear in the conjunctiva on either side in each eye. Corneal epithelium becomes Keratinised, opaque and may become softened and ulcerated, condition described as keratomalacia.

• Respiratory tract: Keratinisation occurring in the mucous membrane of respiratory tract leads to increased susceptibility to infection and lowered resistance to disease.

• Urinary tract: Keratinisation of UT leads to calculi ‘formation’.

4. Role in Bone and Teeth Formation

It plays role in construction of normal bone. Deficiency results in slowing of endochondral bone formation and decreased osteoblastic activity, the bone becomes cancellous losing their fine structural details. Mechanical damage to the brain and cord due to arrested limits of bony frame work and cranium and vertebral column in which it has to grow. Teeth become unhealthy due to thinning of enamel and chalky deposits on surface.

5. Growth

Vitamin A alongwith other vitamin is principally involved in growth. Its role in cell differentiation and cell division has been proved beyond doubt.

6. Metabolism

It may be involved in protein synthesis and may play a role in metabolism of DNA.

MECHANISM OF ACTION  OF VITAMIN A

Vision:Vitamin A (all-trans retinol) is converted in the retina to the 11-cis-isomer of retinaldehyde or 11-cis-retinal. 11-cis-retinal functions in the retina in the transduction of light into the neural signals necessary for vision. 11-cis-retinal, while attached to opsin in rhodopsin is isomerized to all-trans-retinal by light. This is the event that triggers the nerve impulse to the brain which allows for the perception of light. All-trans-retinal is then released from opsin and reduced to all-trans-retinol. All-trans-retinol is isomerized to 11-cis-retinol in the dark, and then oxidized to 11-cis-retinal. 11-cis-retinal recombines with opsin to re-form rhodopsin. Night blindness or defective vision at low illumination results from a failure to re-synthesize 11-cis retinal rapidly. 
Epithelial differentiation: The role of Vitamin A in epithelial differentiation, as well as in other physiological processes, involves the binding of Vitamin A to two families of nuclear retinoid receptors (retinoic acid receptors, RARs; and retinoid-X receptors, RXRs). These receptors function as ligand-activated transcription factors that modulate gene transcription. When there is not enough Vitamin A to bind these receptors, natural cell differentiation and growth are interrupted.

DEFICIENCY DISORDERS OF VITAMIN A

Vitamin A deficiency (VAD) or hypovitaminosis A is a lack of vitamin A in blood and tissues. It is common in poorer countries, but rarely is seen in more developed countries. Nyctalopia (night blindness) is one of the first signs of VAD. Xerophthalmia, keratomalacia, and complete blindness can also occur since vitamin A has a major role in phototransduction. The three forms of vitamin A include retinols, beta-carotenes, and carotenoids.

Vitamin A deficiency is the leading cause of preventable childhood blindness, and is critical to achieving Millennium Development Goal 4 to reduce child mortality.About 250,000 to 500,000 malnourished children in the developing world go blind each year from a deficiency of vitamin A, around half of whom die within a year of becoming blind. The United Nations Special Session on Children in 2002 set a goal of the elimination of VAD by 2010.

Groups at Risk of Vitamin A Inadequacy

The following groups are among those most likely to have inadequate intakes of vitamin A.

•     Premature Infants

Causes and symptoms

In developed countries, clinical vitamin A deficiency is rare in infants and occurs only in those with malabsorption disorders . However, preterm infants do not have adequate liver stores of vitamin A at birth and their plasma concentrations of retinol often remain low throughout the first year of life Preterm infants with vitamin A deficiency have an increased risk of eye, chronic lung, and gastrointestinal diseases .

•     Infants and Young Children in Developing Countries

Causes and symptoms

In developed countries, the amounts of vitamin A in breast milk are sufficient to meet infants’ needs for the first 6 months of life. But in women with vitamin A deficiency, breast milk volume and vitamin A content are suboptimal and not sufficient to maintain adequate vitamin A stores in infants who are exclusively breastfed , The prevalence of vitamin A deficiency in developing countries begins to increase in young children just after they stop breastfeeding The most common and readily recognized symptom of vitamin A deficiency in infants and children is xerophthalmia.

•     Pregnant and Lactating Women in Developing Countries

Causes and symptoms

Pregnant women need extra vitamin A for fetal growth and tissue maintenance and for supporting their own metabolism . The World Health Organization estimates that 9.8 million pregnant women around the world have xerophthalmia as a result of vitamin A deficiency . Other effects of vitamin A deficiency in pregnant and lactating women include increased maternal and infant morbidity and mortality, increased anemia risk, and slower infant growth and development.

§  People with Cystic Fibrosis

Causes and symptoms

Most people with cystic fibrosis have pancreatic insufficiency, increasing their risk of vitamin A deficiency due to difficulty absorbing fat . Several cross-sectional studies found that 15%–40% of patients with cystic fibrosis have vitamin A deficiency . However, improved pancreatic replacement treatments, better nutrition, and caloric supplements have helped most patients with cystic fibrosis become vitamin A sufficient . Several studies have shown that oral supplementation can correct low serum beta-carotene levels in people with cystic fibrosis, but no controlled studies have examined the effects of vitamin A supplementation on clinical outcomes in patients with cystic fibrosis

•     Cancer

Causes and symptoms

Because of the role vitamin A plays in regulating cell growth and differentiation, several studies have examined the association between vitamin A and various types of cancer. However, the relationship between serum vitamin A levels or vitamin A supplementation and cancer risk is unclear.

•     Age-Related Macular Degeneration

Causes and symptoms

Age-related macular degeneration (AMD) is a major cause of significant vision loss in older people. AMD’s etiology is usually unknown, but the cumulative effect of oxidative stress is postulated to play a role. If so, supplements containing carotenoids with antioxidant functions, such as beta-carotene, lutein, and zeaxanthin, might be useful for preventing or treating this condition. Lutein and zeaxanthin, in particular, accumulate in the retina, the tissue in the eye that is damaged by AMD.

Treatment for subclinical VAD includes the consumption of vitamin A–rich foods, such as liver, beef, chicken, eggs, fortified milk, carrots, mangoes, sweet potatoes, and leafy green vegetables.

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