Conversion of beta-carotene to retinal pigment

Vitamin A and its active metabolite retinoic acid (RA)(1) play a major role in development, differentiation, and support of various tissues and organs of numerous species. To assure the supply of target tissues with vitamin A, long-lasting stores are built in the liver from which retinol can be transported by a specific protein to the peripheral tissues to be metabolized to either RA or reesterified to form intracellular stores. Vitamin A cannot be synthesized de novo by animals and thus has to be taken up from animal food sources or as provitamin A carotenoids, the latter being converted by central cleavage of the molecule to retinal in the intestine. The recent demonstration that the responsible beta-carotene cleaving enzyme beta,beta-carotene 15,15'-monooxygenase (Bcmo1) is also present in other tissues led to numerous investigations on the molecular structure and function of this enzyme in several species, including the fruit fly, chicken, mouse, and also human. Also a second enzyme, beta,beta-carotene-9',10'-monooxygenase (Bcmo2), which cleaves beta-carotene eccentrically to apo-carotenals has been described. Retinal pigment epithelial cells were shown to contain Bcmo1 and to be able to cleave beta-carotene into retinal in vitro, offering a new pathway for vitamin A production in another tissue than the intestine, possibly explaining the more mild vitamin A deficiency symptoms of two human siblings lacking the retinol-binding protein for the transport of hepatic vitamin A to the target tissues. In addition, alternative ways to combat vitamin A deficiency of specific targets by the supplementation with beta-carotene or even molecular therapies seem to be the future.