Retinoic acid is a member of the over 4,000-strong family of retinoids, which are compounds derived from retinol or vitamin A, or compounds structurally similar to it. Vitamin A itself is derived only from food, and cannot be made in the body of any animal. It is esterified and stored in the liver, the richest source of vitamin A apart from supplements.
Retinoic acid is synthesized from retinol via two enzymatic reactions, involving first reversible oxidation of retinol to retinal, and then a second oxidation, this time irreversibly, to retinoic acid. It is a light-sensitive compound, like other retinoids, because of the alternating double bonds between the carbon atoms in its hydrophobic tail, which is attached to a 6-carbon ring. The low molecular weight of the compound also makes it highly fat-soluble, which means it easily diffuses across cell membranes.
Retinoids are thus important biological molecules, which act in cell growth, epithelial cell growth and maturation, apoptosis and immunologic function, and are vital in embryonic life for organ development. It is also key for visual function. Retinoids like retinoic acid help to transform cell types from the proliferative profile to the maturation profile, by inducing differentiation.
Retinoic acid is bound in the cell by cellular retinoic acid binding protein (CRABP) and inside the nucleus by two types of receptors, the retinoic acid receptor (RAR) and the retinoid X receptor (RXR). There are various biologically active forms of retinoic acid, and they isomerize under physiological conditions. The different isomers act on different receptors.
All retinoids have a variety of uses in visual and skin conditions, and in cancer therapeutics. A low vitamin A intake is associated with a higher cancer risk. Abnormal RA receptors are also linked to cancer development. Animal studies show that retinoids suppress cancerous changes. Human studies confirm that retinoid administration suppresses cancers of the breast, lung and liver; reverses premalignant changes and induces differentiation of the myeloid cell series in blood.
All-trans RA, or tretinoin, is the most abundant natural isoform, and has been found to be an active agent against a wide range of cancers of the lung, brain, kidney, blood cells, lymphatic tissue, uterine cervix and skin. Another form of retinoic acid, called 9-cis retinoin, or isotretinoin, is also used in the treatment of skin lesions of Kaposi’s sarcoma, as well as for cancers of the breast and prostate.
Vitamin A is found in all dark green, yellow and red vegetables as well as red or yellow non-citrus fruits. It is also richly found in fish like sardines and cod, and in liver and fish oils. Retinoic acid has been extensively used to prevent and treat photoaged skin and to treat psoriasis. Both etretinoin and isotretinoin, two synthetic forms of vitamin A, are highly teratogenic. Etretinoin is not available for medical use, while isotretinoin is strictly controlled.
References
- http://www.cellandbioscience.com/content/2/1/11
- http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2632951/
- http://www.ncbi.nlm.nih.gov/pubmed/21073338
- http://www.sigmaaldrich.com/technical-documents/articles/biofiles/retinoic-acid-and.html
- http://web.stanford.edu/group/hopes/cgi-bin/hopes_test/retinoic-acid-ra/
- http://www.ncbi.nlm.nih.gov/pubmed/16243124
- https://embryo.asu.edu/pages/retinoids-teratogens
Further Reading
- All Retinoic Acid Content
- Retinoic Acid Biological Activity
Last Updated: Aug 23, 2018
Written by
Dr. Liji Thomas
Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.
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