Visual cycle: Vitamin A is a component of the visual pigments of rod and cone cells. Rhodopsin, the visual pigment of the rod cells in the retina, consists of 11-cis retinal bound to the protein opsin (see Fig. 28.19). When rhodopsin, a G protein–coupled receptor, is exposed to light, a series of photochemical isomerizations occurs, which results in the bleaching of rhodopsin and release of all-trans retinal and opsin. This process activates the G protein transducin, triggering a nerve impulse that is transmitted by the optic nerve to the brain. Regeneration of rhodopsin requires isomerization of all-trans retinal back to 11-cis retinal. All-trans retinal is reduced to all-trans retinol, esterified, and isomerized to 11-cis retinol that is oxidized to 11-cis retinal. The latter combines with opsin to form rhodopsin, thus completing the cycle. Similar reactions are responsible for color vision in the cone cells.
2.
Epithelial cell maintenance: Vitamin A is essential for normal differentiation of epithelial tissues and mucus secretion and, thus, supports the body’s barrier-based defense against pathogens.
3.
Reproduction: Retinol and retinal are essential for normal reproduction, supporting spermatogenesis in the male and preventing fetal resorption in the female. Retinoic acid is inactive in maintaining reproduction and in the visual cycle but promotes growth and differentiation of epithelial cells.
F. Distribution
Liver, kidney, cream, butter, and egg yolk are good sources of preformed vitamin A. Yellow, orange, and dark-green vegetables and fruits are good sources of the carotenes (provitamin A).
G. Requirement
The RDA for adults is 900 retinol activity equivalents (RAE) for males and 700 RAE for females. In comparison, 1 RAE = 1 µg of retinol, 12 µg of β carotene, or 24 µg of other carotenoids.
H. Clinical indications for vitamin A
Although chemically related, retinoic acid and retinol have distinctly different therapeutic applications. Retinol and its carotenoid precursor are used as dietary supplements, whereas various forms of retinoic acid are useful in dermatology (Fig. 28.21).
1.
Deficiency: Vitamin A, administered as retinol or retinyl esters, is used to treat patients who are deficient in the vitamin. Night blindness (nyctalopia) is one of the earliest signs of vitamin A deficiency. The visual threshold is increased, making it difficult to see in dim light. Prolonged deficiency leads to an irreversible loss in the number of visual cells. Severe deficiency leads to xerophthalmia, a pathologic dryness of the conjunctiva and cornea, caused, in part, by increased keratin synthesis. If untreated, xerophthalmia results in corneal ulceration and, ultimately, in blindness because of the formation of opaque scar tissue. The condition is most commonly seen in children in developing tropical countries. Over 500,000 children worldwide are blinded each year by xerophthalmia caused by insufficient vitamin A in the diet.
2.
Skin conditions: Dermatologic problems such as acne are effectively treated with retinoic acid or its derivatives (see Fig. 28.21). Mild cases of acne and skin aging are treated with tretinoin (all-trans retinoic acid). Tretinoin is too toxic for systemic (oral) administration in treating skin conditions and is confined to topical application. [Note: Oral tretinoin is used in treating acute promyelocytic leukemia.] In patients with severe cystic acne unresponsive to conventional therapies, isotretinoin (13-cis retinoic acid) is administered orally. An oral synthetic retinoid is used to treat psoriasis.