Retinol

Lipidomics Gateway (28 September 2011) [doi:10.1038/lipidmaps.2011.26]

Retinol and its metabolites mediate a myriad of physiological functions, from vision to reproduction.

The structure of retinol (also known as vitamin A). Visit retinol in the LIPID MAPS structure database for more molecular information.

The prenol lipid retinol (also known as vitamin A) is the immediate precursor to an aldehyde metabolite, retinal, which is required for visual function, and an acid metabolite, retinoic acid, which regulates many other, different, physiological functions. Structurally, retinol and its metabolites possess a β-ionone ring and a polyunsaturated side chain to which an alcohol, aldehyde or carboxylic acid group is attached.

Retinol is obtained directly from foods of animal origin, such as liver and eggs, and indirectly from carotenoids (including α-carotene, β-carotene, γ-carotene or β-cryptoxanthin), which are found in carrots and spinach. Any excess of this fat-soluble vitamin is stored in the liver and fatty tissues as retinyl esters, which can be readily hydrolysed to retinol, when necessary, and transported in the blood bound to retinol-binding protein. However, vitamin A toxicity can occur because, being fat-soluble, it is difficult to eliminate from the body.

Vitamin A deficiency is the main cause of blindness in the developing world, highlighting the key role of retinal in vision. In photoreceptor cells within the retina, 11-cis-retinal binds to different opsin receptors ¹ ; when it absorbs light, it is isomerized to form 11-trans-retinal. This physical change triggers a chain of events that ultimately alters the signals sent along the optic nerve to the visual centre of the brain. In addition to this key role in vision, retinal has recently been reported to inhibit adipogenesis ² .

Retinoic acid mediates an abundance of physiological effects, including immunity, reproduction and embryonic development, primarily through gene transcription. Upon binding its all-trans-retinoic acid ligand, the retinoic acid receptor heterodimerizes with a retinoid X receptor and binds to retinoic acid response elements on DNA to modify the expression of target genes. More recently, a role for retinoic acid in regulating protein translation has also been discovered ³ .

Although its metabolites are thought to be responsible for the majority of effects, retinol itself also has distinct biological activities ¹ . For example, retinol is transported into cells by the STRA6 membrane transporter, which has been shown to induce signal transduction leading to gene transcription in response to association with the retinol–RBP complex ⁴ .

The finding that vitamin A administration can decrease childhood mortality by 20–70% in developing countries underscores the impact of retinol on human health, and has led to schemes aimed at enriching staple foods with vitamin A ¹ . Similarly, retinoid therapy is advocated for several diseases, including cancer, metabolic diseases and dermatological diseases.

Katrin Legg

References:

1. Sun, H. Membrane receptors and transporters involved in the function and transport of vitamin A and its derivatives.
   Biochim. Biophys. Acta (2011). doi:10.1016/j.bbalip.2011.06.010
2. Ziouzenkova, O. et al. Retinaldehyde represses adipogenesis and diet-induced obesity.
   Nat. Med. 13, 695-702 (2007). doi:10.1038/nm1587
3. Chen, N., Onisko, B. & Napoli, J.L. The nuclear transcription factor RARalpha associates with neuronal RNA granules and suppresses translation.
   J. Biol. Chem. 283, 20841-20847 (2008). doi:10.1074/jbc.M802314200
4. Berry, D.C., Jin, H., Majumdar, A. & Noy, N. Signaling by vitamin A and retinol-binding protein regulates gene expression to inhibit insulin responses.
   Proc. Natl Acad. Sci. USA. 108, 4340-4345 (2011). doi:10.1073/pnas.1011115108