No abstract

The macular region of the primate retina is yellow in color due to the presence of the macular pigment, composed of two dietary xanthophylls, lutein and zeaxanthin, and another xanthophyll, meso-zeaxanthin. The latter is presumably formed from either lutein or zeaxanthin in the retina. By absorbing blue-light, the macular pigment protects the underlying photoreceptor cell layer from light damage, possibly initiated by the formation of reactive oxygen species during a photosensitized reaction. There is ample epidemiological evidence that the amount of macular pigment is inversely associated with the incidence of age-related macular degeneration, an irreversible process that is the major cause of blindness in the elderly. The macular pigment can be increased in primates by either increasing the intake of foods that are rich in lutein and zeaxanthin, such as dark-green leafy vegetables, or by supplementation with lutein or zeaxanthin. Although increasing the intake of lutein or zeaxanthin might prove to be protective against the development of age-related macular degeneration, a causative relationship has yet to be experimentally demonstrated.

No abstract

Previous studies have shown that ␤-carotene 15,15-monooxygenase catalyzes the cleavage of ␤-carotene at the central carbon 15,15-double bond but cleaves lycopene with much lower activity. However, expressing the mouse carotene 9,10-monooxygenase (CMO2) in ␤-carotene/lycopene-synthesizing and -accumulating Escherichia coli strains leads to both a color shift and formation of apo-10-carotenoids, suggesting the oxidative cleavage of both carotenoids at their 9,10-double bond. Here we provide information on the biochemical characterization of CMO2 of the ferret, a model for human carotenoid metabolism, in terms of the kinetic analysis of ␤-carotene/lycopene cleavage into ␤-apo-10-carotenal/apo-10-lycopenal in vitro and the formation of apo-10-lycopenoids in ferrets in vivo. We demonstrate that the recombinant ferret CMO2 catalyzes the excentric cleavage of both all-trans-␤-carotene and the 5-cis-and 13-cis-isomers of lycopene at the 9,10-double bond but not all-trans-lycopene. The cleavage activity of ferret CMO2 was higher toward lycopene cis-isomers as compared with ␤-carotene as substrate. Iron was an essential co-factor for the reaction. Furthermore, all-trans-lycopene supplementation in ferrets resulted in significant accumulation of cis-isomers of lycopene and the formation of apo-10-lycopenol, as well as upregulation of the CMO2 expression in lung tissues. In addition, in vitro incubation of apo-10-lycopenal with the post-nuclear fraction of hepatic homogenates of ferrets resulted in the production of both apo-10-lycopenoic acid and apo-10-lycopenol, respectively, depending upon the presence of NAD ؉ or NADH as cofactors. Our finding of bioconversion of cis-isomers of lycopene into apo-10-lycopenoids by CMO2 is significant because cis-isomers of lycopene are a predominant form of lycopene in mammalian tissues and apo-lycopenoids may have specific biological activities related to human health.Carotenoids are lipophilic plant pigments with polyisoprenoid structures, typically containing a series of conjugated double bonds in the central chain of the molecule, which makes them susceptible to oxidative cleavage, and isomerization from trans to cis forms, with the formation of potentially bioactive metabolites. Knowledge of the biological effects of carotenoids, particularly for the impact of oxidation on these carotenoids and the potential for beneficial effects of small quantities or harmful effects of large quantities of the resulting metabolic products, has been reviewed recently (1). For provitamin A carotenoids, such as ␤-carotene, ␣-carotene, and ␤-cryptoxanthin, central cleavage is a major pathway leading to vitamin A formation (2, 3). This pathway has been substantiated by the cloning of the central cleavage enzyme at their 15,15Ј-double bond, ␤-carotene 15,15Ј-monooxygenase (CMO1, 2 formerly called ␤-carotene 15,15Ј-dioxygenase) in different species (4, 5), further classification of this enzyme as a non-heme iron monooxygenase (6), and recent biochemical and structural characterizations (7-11). Very rece...

No abstract

Plasma carotenoid responses were determined in 36 healthy men and women before and after being fed controlled diets with a moderate amount of fat (26% of total energy) and a high carotenoid content (approximately 16 mg/d) for two 15-d periods. In addition, broccoli (205 g/d) was provided either during the first or the second 15-d residency period in a crossover design. Plasma was digested with lipase and cholesterol esterase, and carotenoids were extracted and measured by using HPLC. Three oxygenated carotenoids (lutein, zeaxanthin, and cryptoxanthin), three hydro-carbon carotenoids (alpha-carotene, all-trans-beta-carotene, and 13-cis-beta-carotene), and four geometric isomers of lycopene (15-cis-, 13-cis-, 9-cis-, and all-trans-lycopene) were separated by using a C30 carotenoid column. A small unidentified peak coeluted with standard 9-cis-beta-carotene and was identified as zeta-carotene (lambda(max) = 400 nm). The concentrations of plasma lutein, cryptoxanthin, alpha-carotene, 13-cis-beta-carotene, all-trans-beta-carotene, and cis- and trans-lycopenes were all significantly increased (P < 0.05) on days 6-16 by the high-fruit and -vegetable diets. The provision of additional broccoli for 5 d to the basic high-carotenoid diet resulted in a further significant increase in the serum concentration of lutein compared with the feeding of the basic high-carotenoid diet alone. Most of the measurable carotenoids of human plasma can be increased by moderate alterations in diet within a short time, although the magnitude of the plasma response may be related to the baseline carotenoid concentrations.

Diminished retinoid signaling, resulting from the suppression of RARbeta gene expression and overexpression of activator protein-1, could be a mechanism to enhance lung tumorigenesis after high-dose beta-carotene supplementation and exposure to tobacco smoke.

No abstract