Structural Biochemistry/Chemistry of important organic molecules in Biochemistry/Vitamin A

Overview

Vitamin A is a fat-soluble vitamin that is derived from two sources: preformed retinoids and provitamin carotenoids. Retinoids, such as retinal and retinoic acid, are found in animal sources such as liver, kidney, eggs, and dairy produce. Carotenoids, such as beta-carotene (which has the highest vitamin A activity), are found in plants such as dark or yellow vegetables and carrots.

Natural retinoids are present in all living organisms, either as preformed vitamin A or as carotenoids, and are required for biological processes such as vision and cellular growth. A major biologic function of vitamin A (as the metabolite retinal) is in the visual cycle. Research also suggests that vitamin A may reduce the mortality rate from measles, prevent some types of cancer, aid in growth and development, and improve immune function.

Recommended dietary allowance (RDA) levels for vitamin A oral intake have been established by the U.S. Institute for Medicine of the National Academy of Sciences to prevent deficiencies in vitamin A. At recommended doses, vitamin A is generally considered nontoxic. Excess dosing may lead to acute or chronic toxicity.

Vitamin A deficiency is rare in industrialized nations but remains a concern in developing countries, particularly in areas where malnutrition is common. Prolonged deficiency can lead to xerophthalmia (dry eye) and ultimately to night blindness or total blindness, as well as to skin disorders, infections (such as measles), diarrhea, and respiratory disorders.

Functions of Vitamin A

Gene Regulation

Vitamin A, while it is in its retinoic acid form, plays a very crucial role when it comes to gene transcription. Retinoic acid regulates gene transcription by binding to nuclear receptors known as retinoic acid receptors, or also known as RARs. These RARs are bound to DNA as heterodimers with the appropriate retinoid receptors. When RAR binds to these specific retinoid receptors found in the DNA, known as RXRs, they form a a heterodimer known as a RAR-RXR complex before completely binding to DNA. It should be noted that the receptors found on DNA does not necessarily need to bind to RAR, but can form homodimers known as RXR-RXRs that can then form larger heterodimers with many other nuclear receptors. However, the RAR-RXR heterodimer recognizes retinoic acid response elements known as RAREs on DNA while RXR-RXR homodimers can recognize retinoid X response elements on the DNA. The heterodimers of RXR can bind to various distance response elements on the DNA to control processees not regulated specifically by Vitamin A. In other words, the alternate forms of vitamin A, specifically retinoic acid, can form these heterodimers with retinoic receptors to form complexes of response systems that can then regulate greater processes that normal Vitramin A could not do alone. For examples, upon initial binding and creation of the RAR-RXR complex, the receptors undergo a conformational change that causes co-repressors to dissociate to receptors. At this point, coactivators can then bind to the receptor complex and help loosen chromatin structures from histones. This response that is regulated by the retionic-retionic receptor complex (RAR-RXR) can regulate expression of target genes by release and attachment of various corepressors and coactivators.

Reference

http://www.mayoclinic.com/health/vitamin-a/NS_patient-vitamina