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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #197717
Title: THE BIOCHEMICAL CHARACTERIZATION OF FERRET CAROTENE-9', 10'-MONOOXYGENASE CATALYZING CLEAVAGE OF CAROTENOIDS IN VITRO AND IN VIVO

Author
item HU, KANG-QUAN - TUFTS/HNRCA
item LIU, CHUN - TUFTS/HNRCA
item ERNST, HANSGEORG - BASF
item KRINSKY, NORMAN - TUFTS/HNRCA
item Russell, Robert
item Wang, Xiang-Dong

Submitted to: Journal of Biological Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/1/2006
Publication Date: 7/14/2006
Citation: Hu, K., Liu, C., Ernst, H., Krinsky, N.I., Russell, R.M., Wang, X. 2006. The biochemical characterization of ferret carotene-9', 10'-monooxygenase catalyzing cleavage of carotenoids in vitro and in vivo. Journal of Biological Chemistry. 281:19327-19338.

Interpretive Summary: Previous studies have shown that beta-carotene 15,15'-monooxygenase (CMO1) converts beta-carotene into vitamin A. However, it is unknown whether carotene-9’,10’-monooxygenase (CMO2) converts beta-carotene and lycopene into other metabolites. Here we provide information on the biochemical characterization of CMO2 of the ferret, a model for human carotenoid metabolism, in terms of the analysis of b-carotene/lycopene conversion into other metabolites (called beta-apo-10’-carotenal/apo-10’-lycopenal). We demonstrate that the ferret CMO2 can convert both beta-carotene and the isomers of lycopene. Furthermore lycopene supplementation in ferrets resulted in the formation of apo-10’-lycopenol, as well as up-regulation of the CMO2 expression in lung tissues. 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.

Technical Abstract: Previous studies have shown that beta -carotene 15,15'-monooxygenase (CMO1) catalyzes the cleavage of beta -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 beta-carotene/lycopene-synthesizing and -accumulating E. 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 beta -carotene/lycopene cleavage into beta -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 beta -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 b-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 up-regulation 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.