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Anuj Kumar
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9:15 AM on November 22, 2008
Ram Singh's Answer
Vitamin A is a generic term for a large number of related compounds. Retinol (an alcohol) and retinal (an aldehyde) are often referred to as preformed vitamin A. Retinal can be converted by the body to retinoic acid, the form of vitamin A known to affect gene transcription. Retinol, retinal, retinoic acid, and related compounds are known as retinoids. Beta-carotene and other carotenoids that can be converted by the body into retinol are referred to as provitamin A carotenoids. Hundreds of different carotenoids are synthesized by plants, but only about 10% of them are provitamin A carotenoids (1). The following discussion will focus mainly on preformed vitamin A and retinoic acid.
Function
Vision
The retina is located at the back of the eye. When light passes through the lens, it is sensed by the retina and converted to a nerve impulse for interpretation by the brain. Retinol is transported to the retina via the circulation and accumulates in retinal pigment epithelial cells (diagram). Here, retinol is esterified to form a retinyl ester, which can be stored. When needed, retinyl esters are broken apart (hydrolyzed) and isomerized to form 11-cis-retinol, which can be oxidized to form 11-cis-retinal. 11-cis-retinal can be shuttled across the interphotoreceptor matrix to the rod cell where it binds to a protein called opsin to form the visual pigment, rhodopsin (also known as visual purple). Rod cells with rhodopsin can detect very small amounts of light, making them important for night vision. Absorption of a photon of light catalyzes the isomerization of 11-cis-retinal to all-trans-retinal and results in its release. This isomerization triggers a cascade of events, leading to the generation of an electrical signal to the optic nerve. The nerve impulse generated by the optic nerve is conveyed to the brain where it can be interpreted as vision. Once released, all-trans retinal is converted to all-trans-retinol, which can be transported across the interphotoreceptor matrix to the retinal epithelial cell, thereby completing the visual cycle (2). Inadequate retinol available to the retina results in impaired dark adaptation, known as "night blindness."
Regulation of gene expression
Retinoic acid (RA) and its isomers act as hormones to affect gene expression and thereby influence numerous physiological processes. All-trans-RA and 9-cis-RA are transported to the nucleus of the cell bound to cytoplasmic retinoic acid-binding proteins (CRABP). Within the nucleus, RA binds to retinoic acid receptor proteins (diagram). Specifically, all-trans-RA binds to retinoic acid receptors (RAR) and 9-cis-RA binds to retinoid X receptors (RXR). RAR and RXR form RAR/RXR heterodimers; these heterodimers bind to regulatory regions of the chromosome called retinoic acid response elements (RARE). A dimer is a complex of two protein molecules. Heterodimers are complexes of two different proteins, while homodimers are complexes of two of the same protein. Binding of all-trans-RA and 9-cis-RA to RAR and RXR respectively allows the complex to regulate the rate of gene transcription, thereby influencing the synthesis of certain proteins. RXR may also form heterodimers with thyroid hormone receptors (THR) or vitamin D receptors (VDR). In this way, vitamin A, thyroid hormone, and vitamin D may interact to influence gene transcription (3). Through the stimulation and inhibition of transcription of specific genes, retinoic acid plays a major role in cellular differentiation, the specialization of cells for highly specific physiological roles. Many of the physiological effects attributed to vitamin A appear to result from its role in cellular differentiation.
Immunity
Vit amin A is commonly known as the anti-infective vitamin, because it is required for normal functioning of the immune system (4). The skin and mucosal cells (cells that line the airways, digestive tract, and urinary tract) funct
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10:04 AM on November 22, 2008
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