Carotenoids and Vitamin A: An Overview

Summary

Carotenoids are primarily symmetrical, C-40, polyisoprenoid structures with an extensive conjugated double bond system. Although widely distributed in nature, they are synthesized in photosynthetic microorganisms and plants, but not in animals. Hydrocarbon carotenoids are metabolized to a host of products, including retinal, B-apocarotenals, hydroxylated derivatives (the xanthophylls), and keto and epoxy compounds. Some of these derivatives, such as retinal, abscisin and trisporic acid, show pronounced biological activity. Carotenoids function as accessory pigments in photosynthesis, as protective agents against light-induced cell death in microorganisms, and, in the absence of the dietary intake of preformed vitamin A, as an essential dietary source of the vitamin in mammalian growth and development. Carotenoids also have a variety of interesting actions, which may be of therapeutic value but not necessarily of basic physiological significance. Among such actions are their stimulation of the immune response, their inhibition of mutagenesis and cell transformation, and their prevention of leukoplakia and micronuclei formation in the buccal mucosa. Finally, carotenoid intake has been associated with a lower risk of some types of cancer and of cardiovascular incidents. Because of the many effects of carotenoids on biological systems, distinguishing among functions, actions and associations is important.

Vitamin A is a major product of approximately 50 of the roughly 600 characterized natural carotenoids. Dietary vitamin A is derived from both animal and plant sources. Whereas carotenoids are absorbed intact only by a few species, e.g. humans, cows, and birds, vitamin A is efficiently absorbed by all. Vitamin A is not synthesized de novo from small molecules, but is formed only by cleavage of carotenoids. It exists in various biologically active forms, such as retinol, retinyl esters, retinal, retinoic acid, and the β-glucuronides of retinol and of retinoic acid. Vitamin A and its various active forms are inactivated by hydroxylation, epoxidation and chain cleavage. In vivo the most active forms of vitamin A are bound to a set of specific retinoid-binding proteins, some of which serve as nuclear transcription factors (the retinoic acid receptors). Forms of vitamin A function in vision, cellular differentiation and embryological development. Of various retinoids, retinoic acid and several of its chemically synthesized analogs show the most profound effects on cellular differentiation and on embryological development. Vitamin A is required for growth and development, but large amounts cause toxicity. Thus the separation of efficacy from toxicity is a major pharmacological concern. The only naturally occurring compounds with a high efficacy/toxicity ratio are retinoyl β-glucuronide and retinyl β-glucuronide.

Thus, the carotenoids and retinoids are a diverse set of compounds with a fascinating spectrum of biological effects. Thus far, their precise modes of action in various physiological processes and therapeutic applications have only partially been elucidated.