retinol

Definition: Retinol (Afaxin) is the animal form of vitamin A. It is a fat-soluble vitamin important in vision and bone growth. Retinol belongs to the family of retinoids.

Retinol is ingested in a precursor form; animal sources (liver and eggs) contain retinyl esters, whereas plants (carrots, spinach) contain pro-vitamin A carotenoids.

Hydrolysis of retinyl esters results in retinol while pro-vitamin A carotenoids can be cleaved to produce retinal. Retinal, also known as retinaldehyde, can be reversibly reduced to produce retinol or it can be irreversibly oxidized to produce retinoic acid.

The best described active retinoid metabolites are 11-cis-retinal and the all-trans and 9-cis-isomers of retinoic acid.

Structure

Many different geometric isomers of retinol are possible as a result of either a trans or cis configuration of four of the five double bonds found in the polyene chain.

The cis isomers are less stable and can readily convert to the all-trans configuration (as seen in the structure of all-trans-retinol shown here). Nevertheless, some cis isomers are found naturally and carry out essential functions. For example, the 11-cis-retinal isomer is the chromophore of rhodopsin, the vertebrate photoreceptor molecule. Rhodopsin is comprised of the 11-cis-retinal covalently linked via a Schiff base to the opsin protein (either rod opsin or blue, red or green cone opsins).

The process of vision relies on the light-induced isomerisation of the chromophore from 11-cis to all-trans resulting in a change of the conformation and activation of the photoreceptor molecule.

One of the earliest signs of vitamin A deficiency is night-blindness followed by decreased visual acuity.

Many of the non-visual functions of vitamin A are mediated by retinoic acid, which regulates gene expression by activating intracellular retinoic acid receptors.

The non-visual functions of vitamin A are essential in the immunological function, reproduction and embryonic development of vertebrates as evidenced by the impaired growth, susceptibility to infection and birth defects observed in populations receiving suboptimal vitamin A in their diet.

Functions

 Embryology - Retinoic acid via the retinoic acid receptor influences the process of cell differentiation, hence, the growth and development of embryos. During development there is a concentration gradient of retinoic acid along the anterior-posterior (head-tail) axis. Cells in the embryo respond differently to retinoic acid depending on the amount present. For example, in vertebrates the hindbrain transiently forms eight rhombomers and each rhombomere has a specific pattern of genes being expressed. If retinoic acid is not present the last four rhombomeres do not develop. Instead rhombomeres 1-4 grow to cover the same amount of space as all eight would normally occupy. Retinoic acid has its effects by turning on a differential pattern of Hox genes which encode different homeodomain transcription factors which in turn can turn on cell type specific genes. Deletion of the Hox-1 gene from rhombomere 4 makes the neurons growing in that region behave like neurons from rhombomere 2. The retina is also patterned by retinoic acid, with a concentration gradient that is high on the ventral side of the retina and low on the dorsal side.

 Stem cell biology - Retinoic acid is an influential factor used in differentiation of stem cells to more committed fates, echoing retinoic acid’s importance in natural embryonic developmental pathways. It is thought to initiate differentiation into a number of different cell lineages by unsequestering certain sequences in the genome. It has numerous applications in a plethora of stem cell differentiation protocols; amongst these are the differentiation of human embryonic stem cells to posterior foregut lineages and also to functional motor neurons.

 Vision - Vitamin A is required in the production of rhodopsin, the visual pigment used in low light levels. This is why eating foods rich in vitamin A is said to allow an individual to see in the dark.

 Epithelial Cells - Vitamin A is essential for the correct functioning of epithelial cells. In Vitamin A deficiency, mucus-secreting cells are replaced by keratin producing cells, leading to xerosis.

 Glycoprotein synthesis - Glycoprotein synthesis requires adequate Vitamin A status. In severe Vitamin A deficiency, lack of glycoproteins may lead to corneal ulcers or liquefaction.

 Immune System - Vitamin A is essential to maintain intact epithelial tissues as a physical barrier to infection; it is also involved in maintaining a number of immune cell types from both the innate and acquired immune systems. These include the lymphocytes (B-cells, T-cells, and natural killer cells), as well as many myelocytes (neutrophils, macrophages, and myeloid dendritic cells).

 Hematopoiesis - Vitamin A may be needed for normal haematopoiesis; deficiency causes abnormalities in iron metabolism.

 Growth - Vitamin A affects the production of human growth hormone. (GH)

See also

 retinitis pigmentosa

References

 Vitamin A controls epithelial/mesenchymal interactions through Ret expression. Nat Genet. 2001 Jan;27(1):74-8. PMID: 11138002