Vitamin A plays a role in a variety of functions throughout the body, such as:
- Vision
- Gene transcription
- Immune function
- Embryonic development and reproduction
- Bone metabolism
- Haematopoiesis
- Skin health
- Antioxidant Activity
Vision
The role of vitamin A in the vision cycle is specifically related to the retinal form. Within the eye, 11-''cis''-retinal is bound to rhodopsin (rods) and iodopsin (cones) at conserved lysine residues. As light enters the eye the 11-''cis''-retinal is isomerized to the all-"trans" form. The all-"trans" retinal dissociates from the opsin in a series of steps called bleaching. This isomerization induces a nervous signal along the optic nerve to the visual center of the brain. Upon completion of this cycle, the all-"trans"-retinal can be recycled and converted back to the 11-"cis"-retinal form via a series of enzymatic reactions. Additionally, some of the all-"trans" retinal may be converted to all-"trans" retinol form and then transported with an interphotoreceptor retinol-binding protein (IRBP) to the pigment epithelial cells. Further esterification into all-"trans" retinyl esters allow this final form to be stored within the pigment epithelial cells to be reused when needed.
Gene transcription
Vitamin A, in the retinoic acid form, plays an important role in gene transcription. Once retinol has been taken up by a cell, it can be oxidized to retinal (by retinol dehydrogenases) and then retinal can be oxidized to retinoic acid (by retinal oxidase). The conversion of retinal to retinoic acid is an irreversible step, meaning that the production of retinoic acid is tightly regulated, due to its activity as a ligand for nuclear receptors. The RAR-RXR heterodimer recognizes retinoid acid response elements (RAREs) on the DNA whereas the RXR-RXR homodimer recognizes retinoid "X" response elements (RXREs) on the DNA. The other RXR heterodimers will bind to various other response elements on the DNA. Isotretinoin is a teratogen and its use is confined to medical supervision.
Retinal/retinol versus retinoic acid
Vitamin A deprived rats can be kept in good general health with supplementation of retinoic acid. This reverses the growth-stunting effects of vitamin A deficiency, as well as xerophthalmia. However, such rats show infertility (in both male and females) and continued degeneration of the retina, showing that these functions require retinal or retinol, which are intraconvertable but which cannot be recovered from the oxidized retinoic acid.
Further Reading
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